Archive for May, 2021

CRANFORD, N.J., May 25, 2021 /PRNewswire/ --Citius Pharmaceuticals, Inc. ("Citius" or the "Company") (Nasdaq: CTXR), a biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products with a focus on anti-infective products in adjunct cancer care, unique prescription products and stem cell therapy, today announced that it has received the Best Poster Award at the prestigious International Society for Cell and Gene Therapy (ISCT) 2021 Annual Meeting.

The poster, titled "Novel Induced-Mesenchymal Stem Cells (i-MSCs) Attenuate Severity of ARDS in Septic Sheep," will be presented today, May 25, 2021 by Dr. Perenlei Enkhbaatar, Professor and Director of the Translational Intensive Care Unit at The University of Texas Medical Branch.

"The ISCT annual meeting brings together the brightest minds in cell and gene therapy and highlights cutting edge research in the field," stated Dr. Myron Czuczman, Chief Medical Officer and Executive Vice President of Citius. "We are honored to be selected for the Best Poster Award from among this distinguished peer group. The interim results demonstrate a marked improvement in i-MSC treated animals over control animals in key clinical parameters including: improved oxygenation, less systemic shock, and reduced bacterial burden and vascular injury to the lungs. We are encouraged by the data and welcome the support and engagement of the scientific research community," concluded Dr. Czuczman.

Myron Holubiak, President and Chief Executive Officer of Citius added, "We are grateful to be recognized by our peers for this award as we advance our novel stem cell program for the treatment of ARDS. In parallel to the expansion of our proof-of-concept ARDS sheep study, we are following guidance from the U.S. Food and Drug Administration (FDA) in the development of a cGMP Master Cell Bank of i-MSCs. I am pleased to report that we have completed the development of an i-MSC Accession Cell Bank (ACB) which is to serve as the basis for a scalable cGMP compliant manufacturing capability to support all of our planned pre-clinical and clinical trials. Compared with donor-derived cells that require a continuous supply of new donors, we believe our i-MSCs,derived from a single clonal induced pluripotent stem cell (iPSC), offer multiple advantages including consistent and scalable manufacturing and a potentially limitless supply of i-MSCs to meet our future needs. Moreover, we believe that our i-MSC stem cell program has the potential to meaningfully impact the treatment of ARDS and we appreciate the recognition received from the cell and gene therapy community as we advance our program."

Citius' i-MSCs are derived from iPSCs originating from a qualified single-donor dermal fibroblast, resulting in one homogeneous, validated source for all future cells. A patented synthetic, non-immunogenic mRNA high efficiency cell reprogramming technique is applied to create a clonal iPSC Master Cell Bank from which our i-MSCs are differentiated and expanded to create an i-MSC Accession Cell Bank. Citius has completed the development of its i-MSC ACB and is currently testing (as per FDA guidance) and expanding the cells to create an allogeneic cGMP i-MSC Master Cell Bank to support all future i-MSC needs.

The poster will be available to conference attendees via the conference website. The poster will be available on Citius' website once the event commences.

Conference Details:

Abstract Title:

"Novel Induced-Mesenchymal Stem Cells (i-MSCs) Attenuate Severity of ARDS in Septic Sheep"

Authors:

K. Hashimoto, N. Bazhanov, P. Enkhbaatar, M. Angel, A. Lader, M. Czuczman, and M. Matthay

Abstract Number:

100

Date and Time:

May 25, 2021

Session I

12:30 2:00 PM EDT

Session II

8:00 9:30 PM EDT

About Acute Respiratory Distress Syndrome (ARDS)

ARDS is an inflammatory process leading to build-up of fluid in the lungs and respiratory failure. It can occur due to infection, trauma and inhalation of noxious substances. ARDS accounts for approximately 10% of all ICU admissions and almost 25% of patients requiring mechanical ventilation. Survivors of ARDS are often left with severe long-term illness and disability. ARDS is a frequent complication of patients with COVID-19. ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). Symptoms of ARDS include shortness of breath, rapid breathing and heart rate, chest pain (particularly while inhaling), and bluish skin coloration. Among those who survive ARDS, a decreased quality of life is relatively common.

About Citius Pharmaceuticals, Inc.

Citius is a late-stage biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products, with a focus on anti-infectives in adjunct cancer care, unique prescription products, and stem cell therapy. The Company's lead product candidate, Mino-Lok, an antibiotic lock solution for the treatment of patients with catheter-related bloodstream infections (CRBSIs), is currently enrolling patients in a Phase 3 pivotal superiority trial. Mino-Lok was granted Fast Track designation by the U.S. Food and Drug Administration (FDA). Through its subsidiary, NoveCite, Inc., Citius is developing a novel proprietary mesenchymal stem cell treatment derived from induced pluripotent stem cells (iPSCs) for acute respiratory conditions, with a near-term focus on Acute Respiratory Distress Syndrome (ARDS) associated with COVID-19. For more information, please visit http://www.citiuspharma.com.

Safe Harbor

This press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "plan," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock price. Factors that could cause actual results to differ materially from those currently anticipated are: risks relating to the results of research and development activities, including those for our NoveCite stem cell therapy; uncertainties relating to preclinical and clinical testing; the early stage of products under development; our dependence on third-party suppliers; our ability to successfully undertake and complete clinical trials and the results from those trials for our product candidates; the estimated markets for our product candidates and the acceptance thereof by any market; the ability of our product candidates to impact the quality of life of our target patient populations; our need for substantial additional funds; market and other conditions; risks related to our growth strategy; patent and intellectual property matters; our ability to attract, integrate, and retain key personnel; our ability to obtain, perform under and maintain financing and strategic agreements and relationships; our ability to identify, acquire, close and integrate product candidates and companies successfully and on a timely basis; our ability to procure cGMP commercial-scale supply; government regulation; competition; as well as other risks described in our SEC filings. These risks have been and may be further impacted by Covid-19. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding our business are described in detail in our Securities and Exchange Commission ("SEC") filings which are available on the SEC's website at http://www.sec.gov, including in our Annual Report on Form 10-K for the year ended September 30, 2020, filed with the SEC on December 16, 2020 and updated by our subsequent filings with the SEC. These forward-looking statements speak only as of the date hereof, and we expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law.

Investor Relations for Citius Pharmaceuticals:

Andrew ScottVice President, Special ProjectsT: 908-967-6677 x105E: [emailprotected]

Ilanit AllenVice President, Corporate Communications and Investor RelationsT: 908-967-6677 x113E: [emailprotected]

SOURCE Citius Pharmaceuticals, Inc.

Home

Continue reading here:
Citius Pharmaceuticals Selected to Receive Best Poster Award at the International Society for Cell and Gene Therapy 2021 Annual Meeting - PRNewswire

Founded to meet the future protein demands of an expanding global population, Australias Magic Valley is developing cell-cultured lamb products including mince, strips, steaks and chops. With lambs currently slaughtered at an incredibly young age using traditional farming methods, its founder tells us this particular meat became the obvious choice for the companys first product range.

There is absolutely no need for the mass slaughter of animals for food and hopefully intensive animal agriculture will soon be a thing of the past

Vegconomist spoke with Founder Paul Bevan, who says that he had become frustrated by the pace of change and effectiveness of his own activism so he turned his attention to technology, specifically the development of slaughter-free cultured meat, beginning with lamb.

Utilising induced pluripotent stem-cells and FBS-free media, Magic Valley is able to grow real animal meat from animal cells, using animals such as Lucy, who Paul refers to as cell volunteers.

Eventually we would like to expand into developing cultured meat products for all other animal species

Lucy the lamb is our very special cell donor. From just a tiny skin biopsy less than 4mm in diameter we are able to generate an infinite number of muscle and fat cells without ever having to interfere with an animal again. That is one of the distinct advantages of our technology and using induced pluripotent stem cells.

Meanwhile, Lucy gets to live out the entirety of her natural life (up to 20 years of age) happy and unharmed, blissfully unaware that her cell donation has potentially saved the lives of billions of lambs that would otherwise have been slaughtered at just 6 months of age.

Magic Valleys team consisting of Australias leading scientists have extensive experience in both stem cell biology and livestock production. As part of its ambitions to become a leader in the field, the company also announced this week the onboarding of industry pioneer Dr. Sandhya Sriram, PhD, Co-Founder & CEO of the cell-based crustacean producers Shiok Meats, to its advisory board.

Eventually we would like to expand into developing cultured meat products for all other animal species that have traditionally been farmed for human consumption. With the advancement of this technology, there is absolutely no need for the mass slaughter of animals for food and hopefully intensive animal agriculture will soon be a thing of the past, Bevan commented to vegconomist.

Our immediate goal is to develop the safest, healthiest and tastiest cultured lamb products possible. We know that to be successful, cultured meat products have to become the obvious choice for consumers and that means taste, price & convenience are paramount. We know that ethical or environmental concerns alone are not enough to change consumer behaviour it has to be a better product.

Related

Excerpt from:
Australia's Magic Valley On How to Turn Cells From "Cell Volunteer" Lucy the Lamb Into Lamb Steaks and Chops - vegconomist - the vegan...

Scientists in Japan from fiscal 2023 will applytechnology to createinduced pluripotent stem (iPS) cells to solve the mystery of how people age, saidNobel laureate Shinya Yamanaka, urging the government to continue funding regenerative medicine research.

Yamanaka,who was awarded the 2012 Nobel Prize in Physiology or Medicine jointly with Sir John B. Gurdon,called for continuous investments in the research of technologies based on iPS cells, such as one to rejuvenate aged cells.

The director of Kyoto Universitys Center for iPS Cell Research and Application (CiRA) made the appeal at a meeting of the science and technology ministry on May 11 to discuss governmental support for projects using iPS cells.

He also noted that research institutes and business operators need to boost their cooperation to realize a seamless flow from basic research through commercialization for the development of regenerative medicines.

The point is whether we can harness the total strength of Japan, Yamanaka said.

Yamanaka explained the center's research plans for fiscal 2023 and later, and stressed the essentiality of financial assistance to maintain Japans international competitiveness in the fields on which iPS cell researchers are expected to concentrate.

The government is pouring as much as 110 billion yen ($1 billion) over the 10 years from fiscal 2013 through 2022 into regenerative medicines taking advantage of primarily iPS cells.

As the support plan for 2023 or afterward has yet to be determined, the ministry in March started discussions over the issue.

Yamanaka said the technology to create iPS cells will be applied to ascertain the mechanism of how people age, starting from fiscal 2023.

Genes are injected into skin and blood cells to initialize them so that iPS cells obtain the ability to turn into other cells again. Improving the method is anticipated to be used to stop cells from aging and rejuvenate tissues.

Yamanaka also expressed his intention to make treatments using iPS cells common. Under the plan, the quality, uniformity and costs of iPS cells produced and supplied by the CiRA Foundation will be further improved.

Original post:
Nobel laureate calls for research funds to solve the mystery of aging : The Asahi Shimbun - Asahi Shimbun

CHICAGO, May 25, 2021 /PRNewswire/ -- In-depth analysis and data-driven insights on the impact of COVID-19 included in this global regenerative medicine market report.

The regenerative medicine market is expected to grow at a CAGR of over 30% during the period 20202026.

Key Highlights Offered in the Report:

Key Offerings:

Get your sample today! https://www.arizton.com/market-reports/regenerative-medicine-market-size

Regenerative Medicine Market Segmentation

Regenerative Medicine Market by Application

Regenerative Medicine Market by Product

Regenerative Medicine Market by End-Users

Regenerative Medicine Market Dynamics

Regenerative medicine is expected to evolve and impact the overall healthcare industry in a positive way in the coming years. Among the global pharmaceutical companies, nearly 1000 companies are working on gene therapy, cell therapy, and tissue-engineering therapeutic products. Many companies worldwide have been developing a wide array of scaffolds that can be used in different tissue engineering applications, which cater to patients who require tissue and organ substitutes. The advances in scaffolds are attributable to several innovations in tissue scaffolds, bone scaffolds, and dental scaffolds. Tissue scaffolds basically act by integrating local cells in the desired shape of the scaffold after implantation. The scaffolds are of different types, such as cellusponge scaffolds in which cells are distributed in sponge pores and start growing. Collagen scaffolds have a unique porous network that allows diffusion of nutrients for cell growth, while hydrogel scaffolds have water content similar to natural tissue. Nanofiber scaffolds are transparent and ease cell imaging and quantification of cells.

Key Drivers and Trends fueling Market Growth:

Regenerative Medicine Market Geography

In 2020, North America accounted for a share of over 62% in the global regenerative medicine market. The region is expected to grow at a significant rate during the forecast period due to the highest number of RM companies in the world. The region has nearly 534 of the 987 RM companies worldwide. The growth is primarily attributable to the increasing incidence rates of different types of cancers such as non-Hodgkin lymphoma, Hodgkin lymphoma, melanoma of the skin, leukemia, and rare disorders, including Spinal muscular atrophy and multiple sclerosis. Cancer is the leading cause of death in North America. In 2018, nearly 1.9 million new cancer cases were reported in the North American region, along with 693,000 deaths. In the North American region, the US shows the highest prevalence rate for cancers such as non-Hodgkin lymphoma and other life-threatening rare diseases.

Get your sample today! https://www.arizton.com/market-reports/regenerative-medicine-market-size

Regenerative Medicine Market by Geography

Major Vendors

Other Prominent Vendors

Explore our healthcare & lifesciencesprofile to know more about the industry.

Read some of the top-selling reports:

About Arizton:

AriztonAdvisory and Intelligence is an innovation and quality-driven firm, which offers cutting-edge research solutions to clients across the world. We excel in providing comprehensive market intelligence reports and advisory and consulting services.

We offer comprehensive market research reports on industries such as consumer goods & retail technology, automotive and mobility, smart tech, healthcare, and life sciences, industrial machinery, chemicals and materials, IT and media, logistics and packaging. These reports contain detailed industry analysis, market size, share, growth drivers, and trend forecasts.

Arizton comprises a team of exuberant and well-experienced analysts who have mastered in generating incisive reports. Our specialist analysts possess exemplary skills in market research. We train our team in advanced research practices, techniques, and ethics to outperform in fabricating impregnable research reports.

Mail: [emailprotected]Call: +1-312-235-2040+1 302 469 0707

SOURCE Arizton Advisory & Intelligence

Visit link:
Regenerative Medicine Market Size to Reach Revenues of over USD 27 Billion by 2026 - Arizton - PRNewswire

"Cancer is a disease of genetics, yet clinical practice has struggled to keep pace with rapid advancements in research, particularly with respect to the role of germline genetics. Testing guidelines and medical policy often codify barriers, further lengthening the path to adoption of widespread testing and in some cases restricting access to precision therapies and clinical treatment trials," said Ed Esplin, M.D., Ph.D., FACMG, FACP, clinical geneticist at Invitae. "Research presented at ASCO shows that cancer-linked genetic changes are common across cancer types and when patients do receive germline testing, over two thirds of those with positive results are eligible for changes to their treatment plans. It's clear that incorporating germline testing alongside tumor profiling can help oncologists better tailor treatment for each patient."

Data from 250 pancreatic cancer patients from the landmark INTERCEPT study conducted at the Mayo Clinic found that nearly one in six patients with pancreatic cancer (n=38) showed cancer-linked genetic changes and, importantly, receiving germline testing was associated with improved survival.

A separate study of prostate cancer patients confirmed similar findings in other cancer types that limiting testing deprives patients and clinicians of actionable information. In the first-ever presentation of the PROCLAIM study, which was conducted primarily in community urology clinics, of patients diagnosed with prostate cancer, a significant number of cancer-linked variants were missed if testing was done based on NCCN guidelines. Of the 532 patients with clinician-reported data, nearly half, 45% (n=239), did not meet NCCN criteria. Overall, 59 patients had a cancer-linked variant; one in 10 of them did not meet the criteria (9.6%, n=23), and 12.3% (n=36) of patients met the criteria. When a 12-gene panel was used, only 29 patients were found to have a cancer-linked variant and one third of these patients were missed by guidelines.

A third study showed simply changing medical policy is not enough to drive changes in clinician adoption. In a review of two independent datasets, including commercially insured and Medicare Advantage enrollees, only 3% (n=1,675) of the 55,595 colorectal cancer patients received germline genetic testing, despite medical policy recommending germline genetic testing for all colorectal cancer patients (consistent with the INTERCEPT colorectal cancer study). Of the patients who received testing, 18% (n=143) had a cancer-linked variant and two thirds, or 67% (n=96), of those patients were potentially eligible for precision therapy and/or clinical trials.

"The data have been available for years that show knowing what changes patients have in their genes is beneficial to treating their cancer. Yet the oncology community has been slower to adopt germline testing than tumor profiling, for reasons that are not entirely clear. These data presented at ASCO highlight the need for oncologists to embrace germline genetic testing as routine practice for all cancer patients," said Robert Nussbaum, M.D., chief medical officer at Invitae. "A positive germline genetic result may enable patients to enroll in clinical trials or gain access to new precision medicines. And equally important, the discovery of an inherited variant can alert relatives to seek out earlier cancer screening, helping avoid later-stage diagnoses and offering a treatment benefit if cancer develops."

Invitae aims to help overcome obstacles to the adoption of genetic testing by providing physicians with clinical consults to help interpret results and reducing cost as a barrier to genetic information. Invitae also provides patients direct access to genetic counselors, helping to integrate routine genetic testing into patient care with GIA, a HIPAA-compliant chatbot. Family members are also able to receive no-charge genetic testing if a positive result is found.

Details of the 2021 ASCO presentations:

Oral Abstract Session: Prevention, Risk Reduction, and Hereditary Cancer

Poster Discussion Session: Prevention, Risk Reduction, and Hereditary Cancer

Poster Session: Prevention, Risk Reduction, and Hereditary Cancer

Poster Session: Gastrointestinal Cancer--GastroesophageaI, Pancreatic, and Hepatobiliary

About InvitaeInvitae Corporation(NYSE: NVTA) is a leading medical genetics company whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the company's website atinvitae.com.

Safe Harbor StatementThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the benefits of germline testing and genetic information; and that the data presented at ASCO highlight the need for increased germline testing in all cancer patients regardless of medical policy. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the company's history of losses; the company's ability to compete; the company's failure to manage growth effectively; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2021. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.

Contact:Laura D'Angelo[emailprotected](628) 213-3283

SOURCE Invitae Corporation

http://www.invitae.com

Here is the original post:
Germline genetic testing can benefit all cancer patients as a routine practice in cancer care - PRNewswire

ADELAIDE, Australia, May 25, 2021 /PRNewswire/ --IVF Life Group, a leading group of IVF clinics across Spain, UK, and Germany, will be among the first in Europe to use Artificial Intelligence (AI) to non-invasively assess embryos to determine their genetic integrity. The AI product Life Whisperer, developed by global healthcare company Presagen, uses images of embryos to assess their quality to assist with embryo selection, and ultimately improve IVF outcomes for patients.

Currently, PGT-A genetic testing is one of the most used techniques that requires careful removal of three to five cells from an embryo to analyse its genetic integrity. As the procedure is still not available in some countries, and is quite invasive, Life Whisperer and its AI technology can also assist with this assessment.

Life Whisperer Genetics, which this month received CE Mark in Europe, requires only standard camera images of embryos to assess their genetic integrity. In a US study simulating 91,500 individual patient embryo cohorts, Life Whisperer Genetics ranked the genetically normal (euploid) embryo top in 82% of the patient cohorts. Furthermore, in 96% of the cohorts Life Whisperer Genetics ranked the at least one genetically normal embryo in the top two embryos.

Presagen's first product Life Whisperer Viability assesses the same images of embryos to determine their likelihood of leading to a pregnancy, and is already in use in IVF clinics globally.

Founder & President of IVF Life Group, Dr. Jon Aizpurua said "For the next two months, IVF Life will offer all patients, at no additional cost, the use of both Life Whisperer Genetics and Life Whisperer Viability. Although patients may still elect to use PGT-A testing, Life Whisperer offers an important pre-screen to help us select the best embryos for further genetic testing, transfer, or freezing."

Presagen CEO, Dr Michelle Perugini said "We are excited to be working with IVF Life to enable patients across Europe to access the latest AI technology to help improve their chances of a healthy pregnancy, whilst reducing treatment costs."

Life Whisperer is already authorised for sale in the UK, Canada, Australia, Japan, India, Thailand, New Zealand, Hong Kong, Singapore and Malaysia.

SOURCE Presagen

https://www.presagen.com/

Visit link:
IVF Life the first clinic group in Europe to use Artificial Intelligence to non-invasively assess the genetic integrity of embryos - PRNewswire

A brief analysis of the basic details of Prenatal and Newborn Genetic Testing Market valuation, industry expansion, and market growth opportunities affecting market growth. Likewise, this analysis provides a comprehensive view of technology spending over the forecast period and offers a unique perspective on the Prenatal and Newborn Genetic Testing market in each of the categories included in the survey. The Prenatal and Newborn Genetic Testing Industry Review helps customers assess the challenges and prospects for the company. The investigation includes analyzing the latest keyword business forecast for the relevant period. In addition, the annual industry study contains the latest information on technical developments and market development opportunities depending on the geographic climate. The Prenatal and Newborn Genetic Testing market also includes technology / innovation, a comprehensive outlook on future developments, research and development activities and new products.

Advanced methods are also used to plan the Prenatal and Newborn Genetic Testing industry analysis, as well as the sales and supplier overview of the Prenatal and Newborn Genetic Testing industry. A study of the Prenatal and Newborn Genetic Testing market offers a complete analysis of geographic dynamics, market developments and market shares at the country level of the Prenatal and Newborn Genetic Testing market. A number of key factors were considered during the study, including product definition, market size, product classification, and various ecosystem participants in the Prenatal and Newborn Genetic Testing market.

Get | Download Sample Copy with TOC, Graphs & List of Figures @https://www.verifiedmarketresearch.com/download-sample/?rid=38619

The report covers the following key players in the Prenatal and Newborn Genetic Testing Market:

Abbott Laboratories Bio-Rad Laboratories Qiagen N.V. Natera Illuminaxx

Segmentation of Prenatal and Newborn Genetic Testing Market:

This section of the report provides important information on various types of products and service variants available in the Prenatal and Newborn Genetic Testing market, as well as the scope of their futuristic developments and the associated ability to generate revenue. This section of the report clearly focuses on the usefulness of various products and services available in the market and the diverse developments that meet user preferences.

Aerogel Insulation Market, By Type

Silica Carbon Polymer

Aerogel Insulation Market, By End-User

Oil & gas Performance Coatings Building & Construction Aerospace & Marine Automotive sectors

Get Discount On The Purchase Of This Report @https://www.verifiedmarketresearch.com/ask-for-discount/?rid=38619

Prenatal and Newborn Genetic Testing Market Report Scope

Prenatal and Newborn Genetic Testing Geographic Market Analysis:

This research study draws on multiple layers of data including business analysis (industry trends), high-level market share analysis, supply chain analysis, and brief company profiles that together provide and analyze fundamental perspectives on the competitive landscape. High growth business growth trends and segments, high growth countries, market forces, controls, market drivers, market restrictions and drivers, and restraints. This is the most recent study that includes a strategic assessment as well as an in-depth review of the market plans, approaches, brands and manufacturing capabilities of the world's leading industry leaders.

North America (USA, Canada, Mexico) Europe (Great Britain, France, Germany, Spain, Italy, Central and Eastern Europe, CIS) Asia Pacific (China, Japan, South Korea, ASEAN, India, rest of Asia Pacific) Latin America (Brazil, rest of LA) Middle East and Africa (Turkey, CCG, rest of the Middle East)

Visualize Prenatal and Newborn Genetic Testing Market using Verified Market Intelligence:-

Verified Market Intelligence is our BI-enabled platform for narrative storytelling of this market. VMI offers in-depth forecasted trends and accurate Insights on over 20,000+ emerging & niche markets, helping you make critical revenue-impacting decisions for a brilliant future.

VMI provides a holistic overview and global competitive landscape with respect to Region, Country, and Segment, and Key players of your market. Present your Market Report & findings with an inbuilt presentation feature saving over 70% of your time and resources for Investor, Sales & Marketing, R&D, and Product Development pitches. VMI enables data delivery In Excel and Interactive PDF formats with over 15+ Key Market Indicators for your market.

Visualize Prenatal and Newborn Genetic Testing Market using VMI @https://www.verifiedmarketresearch.com/vmintelligence/

Why the Prenatal and Newborn Genetic Testing Market Report is beneficial?

This in-depth study also includes a detailed description and interpretation of each chapter of the analysis. In order to give the users of this study a detailed insight into the Prenatal and Newborn Genetic Testing industry, we have provided a comprehensive competitive landscape as well as a product inventory of the most important suppliers in different regions. Each chapter of the review is also defined and interpreted in detail in this systematic report. In order to provide users of this factsheet and a detailed overview of the Prenatal and Newborn Genetic Testing industry, we have created a broad competitive landscape as well as a product summary of the major suppliers in various geographic economies.

For More Information or Query or Customization Before Buying, Visit @https://www.verifiedmarketresearch.com/product/prenatal-and-newborn-genetic-testing-market/

About Us: Verified Market Research

Verified Market Research is a leading Global Research and Consulting firm that has been providing advanced analytical research solutions, custom consulting and in-depth data analysis for 10+ years to individuals and companies alike that are looking for accurate, reliable and up to date research data and technical consulting. We offer insights into strategic and growth analyses, Data necessary to achieve corporate goals and help make critical revenue decisions.

Our research studies help our clients make superior data-driven decisions, understand market forecast, capitalize on future opportunities and optimize efficiency by working as their partner to deliver accurate and valuable information. The industries we cover span over a large spectrum including Technology, Chemicals, Manufacturing, Energy, Food and Beverages, Automotive, Robotics, Packaging, Construction, Mining & Gas. Etc.

We, at Verified Market Research, assist in understanding holistic market indicating factors and most current and future market trends. Our analysts, with their high expertise in data gathering and governance, utilize industry techniques to collate and examine data at all stages. They are trained to combine modern data collection techniques, superior research methodology, subject expertise and years of collective experience to produce informative and accurate research.

Having serviced over 5000+ clients, we have provided reliable market research services to more than 100 Global Fortune 500 companies such as Amazon, Dell, IBM, Shell, Exxon Mobil, General Electric, Siemens, Microsoft, Sony and Hitachi. We have co-consulted with some of the worlds leading consulting firms like McKinsey & Company, Boston Consulting Group, Bain and Company for custom research and consulting projects for businesses worldwide.

Contact us:

Mr. Edwyne Fernandes

Verified Market Research

US: +1 (650)-781-4080UK: +44 (753)-715-0008APAC: +61 (488)-85-9400US Toll-Free: +1 (800)-782-1768

Email: sales@verifiedmarketresearch.com

Website:- https://www.verifiedmarketresearch.com/

The rest is here:
Prenatal and Newborn Genetic Testing Market Size And Forecast 2021-2028 | Top Key Players Abbott Laboratories, Bio-Rad Laboratories, Qiagen NV,...

DNA molecule

KTSDESIGN / SCIENCE PHOTO LIBRARY / Getty Images

The Human Genome project was a huge feat for the scientific community at the turn of the 21st century. Charting our entire human genetic code, giving us the opportunity to predict disease and go on to create personalised drug treatments.

The techniques for personal genetic analysis are now relatively cheap and accurate, which has lead to a host of consumer products. Marketed for our individual health risks, personality types, athletic ability and ancestral roots; some of the common health predictors include breast/bowel cancer, diabetes, cholesterol, Parkinson's and Alzheimer's dementia. They include many rare medical conditions, but can also give you information on your eye colour, susceptibility to caffeine/alcohol/obesity, and even forecast the smell of your urine after eating asparagus (this doesn't happen to everyone).

However, despite providing some interesting insights, this convenient 'crystal ball' into our future selves, could equally offer false reassurance, heightened anxiety and some confusion. For example, would you want to live your life in fear of developing Alzheimer's dementia or Parkinson's without any cure on the horizon?

A pre-requisite to most genetic testing in hospital, is a consultant geneticist or a genetic counsellor to help navigate the complex ethical terrain and often misguided interpretation.

The 'Direct to Consumer' genetic test kits, which can be purchased online, usually rely on a saliva sample sent to the lab. It takes a few weeks before the results are delivered online, with detailed analysis and intriguing information. For those of you interested in carrying this out, I would urge you to consider the pros and cons:

PROS:

CONS:

In summary, It may be more important to focus on leading a healthy lifestyle, regardless of the results. Clean diets, regular exercise, careful weight control and avoiding environmental triggers such as smoking/ UV exposure etc. One of the best ways to identify health needs is to understand your family's medical history of mental and physical conditions.

If you have a positive result and have no clear family history of that condition, it is unlikely that you will suffer from it. Inversely, if you have a negative result, but have a strong family history, you may need to ask your GP for further clinical genetic testing. It would be worth first seeking the advice of a genetic counsellor before embarking on any commercial test.

If you are curious about certain traits such as ability to taste bitterness, your ice cream preference, propensity to get dandruff or back hair, then it is informative and interesting, but for health predictability, the industry seems to be outpacing the science. In the future, with Artificial Intelligence and larger databanks, these test should become more reliable.

Dr Tim Lebens is a private GP in Central London, with a subspecialty in health optimisation and latest advances in medicine. Visit his website drlebens.com or follow him on Instagram @_modernmedicine.Although every effort has been made to ensure that all health advice is accurate and up to date, it is for information purposes only and should not replace a visit to your doctor or health care professional.

Subscribe now for a trial offer of 3 issues for 1 plus free digital editions and home delivery.

The Court Circular is your inside track on the latest happenings in the Royal Family, covering the biggest stories shaping the monarchy right now.

by entering your email address, you agree to our privacy policy

Thank You. You have successfully subscribed to our newsletter. You will hear from us shortly.

Sorry, you have entered an invalid email. Please refresh and try again.

More from Tatler

In order to see this embed, you must give consent to Social Media cookies. Open my cookie preferences.

More:
One of London's top doctors weighs up the pros and cons of DIY genetic test kits - Tatler

Request Download SampleAsk For DiscountCompany Profile

Direct-To-Consumer (DTC) Genetic Testing market (2021-2028) current situation and development research possibilities pinpoint to change sharp elements and a point of view on the future of variables ?? or limiting the development of the industry. The Direct-To-Consumer (DTC) Genetic Testing market offers an exhaustive analysis of the market size, participation, degree of development, and Outlook of the Direct-To-Consumer (DTC) Genetic Testing business. This report gives all the fundamental data needed to understand the vital advances in market-to-market spending and the development of Direct-To-Consumer (DTC) Genetic Testing standards for each fragment and locality. The implementation of the action research, the Direct-To-Consumer (DTC) Genetic Testing markets, both in terms of volume and income and this is a factor that is valuable and effective for your business.

Get | Download Sample Copy with TOC, Graphs & List of Figures @https://www.marketresearchintellect.com/download-sample/?rid=248561

Competitive Landscape

The full profile of the companies is mentioned. And the Direct-To-Consumer (DTC) Genetic Testing Market size, production, price, revenue, cost, terrifying margin, gross, sales volume, sales revenue, consumption, buildup rate, Import, Export, Supply, well along strategies and the technological developments they are making are moreover included in the report. Historical data from 2014 to 2019 and predict data from 2021 to 2028.

Direct-To-Consumer (DTC) Genetic Testing Market Leading Key players:

Market segmentation of Direct-To-Consumer (DTC) Genetic Testing market:

Direct-To-Consumer (DTC) Genetic Testing market is divided by type and application. For the period 2021-2028, cross-segment growth provides accurate calculations and forecasts of sales by Type and Application in terms of volume and value. This analysis can help you grow your business by targeting qualified niche markets.

Direct-To-Consumer (DTC) Genetic Testing Market breakdown by type:

Direct-To-Consumer (DTC) Genetic Testing Market breakdown by application:

Get Discount On The Purchase Of This Report @https://www.marketresearchintellect.com/ask-for-discount/?rid=248561

Direct-To-Consumer (DTC) Genetic Testing Market Report Scope

Regional market analysis Direct-To-Consumer (DTC) Genetic Testing can be represented as follows:

For clarity, analysts also segmented the market based on geography. This type of segmentation allows readers to understand the volatile political scenario in different regions and their impact on the global digital Isolator market. The base of geography, the world market of Direct-To-Consumer (DTC) Genetic Testing has segmented as follows:

Visualize Direct-To-Consumer (DTC) Genetic Testing Market using Verified Market Intelligence:-

Verified Market Intelligence is our BI-enabled platform to tell the story of this market. VMI provides in-depth predictive trends and accurate insights into more than 20,000 emerging and niche markets to help you make key revenue impact decisions for a brilliant future.

VMI provides a comprehensive overview and global competitive landscape of regions, countries, and segments, as well as key players in your market. Showcase your market reports and findings with built-in presentation capabilities, providing more than 70% of time and resources for investors, sales and marketing, R & D, and product development. VMI supports data delivery in Excel and interactive PDF formats and provides more than 15 key market indicators for your market.

Visualize Direct-To-Consumer (DTC) Genetic Testing Market using VMI @hhttps://www.marketresearchintellect.com/mri-intelligence/

Scope of the report:-

The scope of the report consolidates an in-depth examination of the global market Reached 2021-2028 with the apprehension given to the company's progress in specific regions.

The Best Organizations Hit Market report is intended to provide our buyers with an overview of the most compelling players in the business. In addition, data on the exposure of various organizations, benefits, net benefit, vital activity and more are introduced through different assets.

For More Information or Query or Customization Before Buying, Visit @https://www.marketresearchintellect.com/product/global-direct-to-consumer-dtc-genetic-testing-market-size-and-forecast//

About Us: Market Research Intellect

Market Research Intellect provides syndicated and customized research reports to clients from various industries and organizations in addition to the objective of delivering customized and in-depth research studies.

We speak to looking logical research solutions, custom consulting, and in-severity data analysis lid a range of industries including Energy, Technology, Manufacturing and Construction, Chemicals and Materials, Food and Beverages. Etc Our research studies assist our clients to make higher data-driven decisions, admit push forecasts, capitalize coarsely with opportunities and optimize efficiency by bustling as their belt in crime to adopt accurate and indispensable mention without compromise.

Having serviced on the pinnacle of 5000+ clients, we have provided expertly-behaved assert research facilities to more than 100 Global Fortune 500 companies such as Amazon, Dell, IBM, Shell, Exxon Mobil, General Electric, Siemens, Microsoft, Sony, and Hitachi.

Contact us:

Mr. Edwyne Fernandes

US: +1 (650)-781-4080UK: +44 (753)-715-0008APAC: +61 (488)-85-9400US Toll-Free: +1 (800)-782-1768

Website: https://www.marketresearchintellect.com/

Continue reading here:
Direct-To-Consumer (DTC) Genetic Testing Market Outlook 2021, Analysis and Forecast to 2028 by Manufacturers| Ancestry, Mapmygenome, Color Genomics,...

Researchers atThe Ohio State University Wexner Medical Centerled an international group of experts that worked together to classify 19 genes associated with dilated cardiomyopathy (DCM) as having high impact on the heart muscle disease.

Researchers believe most of DCM has a genetic background, and at least 30 percent of people with DCM have a family member with the disease. First-degree family members (daughters, sons, brothers, sisters and parents) of a patient with DCM are encouraged to undergo genetic testing for the disease.

However, current genetic testing panels analyze dozens, sometimes hundreds of genes, and they often have limited scientific support, making genetic results clinically difficult to interpret.

When we get results back for a patient with dilated cardiomyopathy, we often see multiple variants in multiple genes. For many genes, we dont know how strongly theyre associated with the condition. By narrowing down the number of genes thought to be disease causing to 19, we can better use genetic information for a diagnosis and give the family a genetic marker to test family members not showing any signs of the disease. Ideally, we can then find who is at risk before they develop DCM, said Elizabeth Jordan, a genetic counselor in the Division of Human Genetics at the Ohio State Wexner Medical Center, and lead author on the study published in the American Heart AssociationsCirculation.

Dilated cardiomyopathy is a condition in which the heart muscle weakens and the left ventricle enlarges. Its the most common cause for patients needing a heart transplant and is responsible for about half of heart failure cases.

For the yearlong study, Stephanie Schulte, head of research and education services at the Health Sciences Library at The Ohio State University, helped develop an initial list of 267 genes after examining various databases. Jordan, along with co-author Laiken Peterson, a genetic counselor atThe Ohio State University College of Medicine, and senior author,Dr. Ray Hershberger, division director of human genetics at the Ohio State Wexner Medical Center and a researcher at theDorothy M.Davis Heart and LungResearch Institute, narrowed the list down to 51, which was evaluated by an international panel of genetic counselors, cardiologists and laboratory scientists.

They used a method developed by the National Institute of Healths Clinical Genome Resource (ClinGen) to determine which genes were most strongly associated with DCM. The research was funded by the NIHs National Human Genome Research Institute and the National Heart, Lung, and Blood Institute.

The researchers evaluated clinical data in humans as well as experimental data in animal models to determine the likelihood that a gene had a role in the disease, Jordan said. Because we often see uncertain genetic results with dilated cardiomyopathy, our hope is that our findings will aid in the interpretation of results of large genetic testing panels, which should help genetic information be more useful in clinical care.

The findings will be extended by research currently being done by the Dilated Cardiomyopathy Consortium, led by Hershberger. In 2015, the NIH awarded $12.4 million to the consortium to study the genetic basis of DCM and lay the foundation for precision medicine for patients.

This was a great example of collaboration with genetic experts across the world. This research, along with additional work being done at The Ohio State University Wexner Medical Center, will provide a better understanding of the role of genetics with DCM and how to treat and prevent it, Hershberger said.

Visit link:
Ohio State researchers name 19 genes associated with heart muscle disease - The Highland County Press

This article was originally published here

Gynecol Oncol. 2021 May 19:S0090-8258(21)00407-8. doi: 10.1016/j.ygyno.2021.05.011. Online ahead of print.

ABSTRACT

PURPOSE: Several professional organizations recommend universal genetic assessment for people with ovarian cancer as identifying pathogenic variants can affect treatment, prognosis, and all-cause mortality for patients and relatives. We sought to evaluate the literature on genetic assessment for women with ovarian cancer and determine if any interventions or patient characteristics drive utilization of services.

METHODS: We searched key electronic databases to identify trials that evaluated genetic assessment for people with ovarian cancer. Trials with the primary aim to evaluate utilization of genetic assessment with or without interventions were included. Eligible trials were subjected to meta-analysis and the moderating influence of health interventions on rates of genetic assessment were examined.

RESULTS: A total of 35 studies were included (19 report on utilization of genetic services without an intervention, 7 with an intervention, and 9 with both scenarios). Without an intervention, pooled estimates for referral to genetic counseling and completion of genetic testing were 39% [CI 27-53%] and 30% [CI 19-44%]. Clinician-facilitated interventions included: mainstreaming of genetic services (99% [CI 86-100%]), telemedicine (75% [CI 43-93%]), clinic-embedded genetic counselor (76% [CI 32-95%]), reflex tumor somatic genetic assessment (64% [CI 17-94%]), universal testing (57% [28-82%]), and referral forms (26% [CI 10-53%]). Random-effects pooled proportions demonstrated that Black vs. White race was associated with a lower rate of genetic testing (26%[CI 17-38%] vs. 40% [CI 25-57%]) as was being un-insured vs. insured (23% [CI 18-28%] vs. 38% [CI 26-53%]).

CONCLUSIONS: Reported rates of genetic testing for people with ovarian cancer remain well below the goal of universal testing. Interventions such as mainstreaming can improve testing uptake. Strategies aimed at improving utilization of genetic services should consider existing disparities in race and insurance status.

PMID:34023131 | DOI:10.1016/j.ygyno.2021.05.011

Visit link:
Achieving universal genetic assessment for women with ovarian cancer: Are we there yet? A systematic review and meta-analysis - DocWire News

Request Download SampleAsk For DiscountCompany Profile

Direct Access Genetic Testing market (2021-2028) current situation and development research possibilities pinpoint to change sharp elements and a point of view on the future of variables ?? or limiting the development of the industry. The Direct Access Genetic Testing market offers an exhaustive analysis of the market size, participation, degree of development, and Outlook of the Direct Access Genetic Testing business. This report gives all the fundamental data needed to understand the vital advances in market-to-market spending and the development of Direct Access Genetic Testing standards for each fragment and locality. The implementation of the action research, the Direct Access Genetic Testing markets, both in terms of volume and income and this is a factor that is valuable and effective for your business.

Get | Download Sample Copy with TOC, Graphs & List of Figures @https://www.marketresearchintellect.com/download-sample/?rid=206225

Competitive Landscape

The full profile of the companies is mentioned. And the Direct Access Genetic Testing Market size, production, price, revenue, cost, terrifying margin, gross, sales volume, sales revenue, consumption, buildup rate, Import, Export, Supply, well along strategies and the technological developments they are making are moreover included in the report. Historical data from 2014 to 2019 and predict data from 2021 to 2028.

Direct Access Genetic Testing Market Leading Key players:

Market segmentation of Direct Access Genetic Testing market:

Direct Access Genetic Testing market is divided by type and application. For the period 2021-2028, cross-segment growth provides accurate calculations and forecasts of sales by Type and Application in terms of volume and value. This analysis can help you grow your business by targeting qualified niche markets.

Direct Access Genetic Testing Market breakdown by type:

Direct Access Genetic Testing Market breakdown by application:

Get Discount On The Purchase Of This Report @https://www.marketresearchintellect.com/ask-for-discount/?rid=206225

Direct Access Genetic Testing Market Report Scope

Regional market analysis Direct Access Genetic Testing can be represented as follows:

For clarity, analysts also segmented the market based on geography. This type of segmentation allows readers to understand the volatile political scenario in different regions and their impact on the global digital Isolator market. The base of geography, the world market of Direct Access Genetic Testing has segmented as follows:

Visualize Direct Access Genetic Testing Market using Verified Market Intelligence:-

Verified Market Intelligence is our BI-enabled platform to tell the story of this market. VMI provides in-depth predictive trends and accurate insights into more than 20,000 emerging and niche markets to help you make key revenue impact decisions for a brilliant future.

VMI provides a comprehensive overview and global competitive landscape of regions, countries, and segments, as well as key players in your market. Showcase your market reports and findings with built-in presentation capabilities, providing more than 70% of time and resources for investors, sales and marketing, R & D, and product development. VMI supports data delivery in Excel and interactive PDF formats and provides more than 15 key market indicators for your market.

Visualize Direct Access Genetic Testing Market using VMI @hhttps://www.marketresearchintellect.com/mri-intelligence/

Scope of the report:-

The scope of the report consolidates an in-depth examination of the global market Reached 2021-2028 with the apprehension given to the company's progress in specific regions.

The Best Organizations Hit Market report is intended to provide our buyers with an overview of the most compelling players in the business. In addition, data on the exposure of various organizations, benefits, net benefit, vital activity and more are introduced through different assets.

For More Information or Query or Customization Before Buying, Visit @https://www.marketresearchintellect.com/product/direct-access-genetic-testing-market-size-and-forecast//

About Us: Market Research Intellect

Market Research Intellect provides syndicated and customized research reports to clients from various industries and organizations in addition to the objective of delivering customized and in-depth research studies.

We speak to looking logical research solutions, custom consulting, and in-severity data analysis lid a range of industries including Energy, Technology, Manufacturing and Construction, Chemicals and Materials, Food and Beverages. Etc Our research studies assist our clients to make higher data-driven decisions, admit push forecasts, capitalize coarsely with opportunities and optimize efficiency by bustling as their belt in crime to adopt accurate and indispensable mention without compromise.

Having serviced on the pinnacle of 5000+ clients, we have provided expertly-behaved assert research facilities to more than 100 Global Fortune 500 companies such as Amazon, Dell, IBM, Shell, Exxon Mobil, General Electric, Siemens, Microsoft, Sony, and Hitachi.

Contact us:

Mr. Edwyne Fernandes

US: +1 (650)-781-4080UK: +44 (753)-715-0008APAC: +61 (488)-85-9400US Toll-Free: +1 (800)-782-1768

Website: https://www.marketresearchintellect.com/

Read more from the original source:
Direct Access Genetic Testing Market Outlook 2021, Analysis and Forecast to 2028 by Manufacturers| 23andme, Myheritage, Labcorp, Myriad Genetics,...

Introduction

Gitelman syndrome (GS) is an autosomal recessive inherited disease initially reported in 1996 and is a rare renal tubular disorder with a prevalence of 1:40,000.1,2 GS is closely associated with the mutations of SLC12A3 gene coding for the thiazide-sensitive sodium-chloride cotransporter (NCCT) of the distal convoluted tubule (DCT).3 To date, more than 400 mutations of SLC12A3 have been identified in GS.48 Most of the mutations are missense, splice-site, nonsense, frameshift, deletions, and insertion mutations.9

The main clinical manifestations of GS are hypokalemic metabolic alkalosis, hypomagnesemia, hypocalciuria and renin-angiotensin-aldosterone system (RAAS) activation. Besides, patients with GS may present with spasticity, muscle weakness, paresthesia, numbness, polyuria, and palpitation.10 However, GS lacks specific clinical manifestations and is easily confused with other diseases such as Bartter syndrome, renal tubular acidosis, and primary aldosteronism.11,12 In addition to history taking and clinical work-up, genetic testing is an important and effective tool for diagnosing GS in clinical practice.13 Here, our present study aimed to analyze the clinical features and genetic characteristics of a Chinese female patient with GS.

A 60-year-old female patient was admitted to the Department of Endocrinology in Tongde Hospital of Shanxi province because of recurrent hypokalemia. She had no obvious clinical symptoms such as palpitations, shortness of breath, muscle weakness of the lower limbs, vomiting, nausea, anorexia, diarrhea, polyphagia and emaciation and denied a history of chronic kidney disease. She was treated with potassium citrate or potassium chloride, but she had no history of other drugs such as diuretics, proton pump inhibitors, and anti-tumor agents.

The patient underwent detailed systemic physical examinations. Fasting blood samples and urine samples were obtained. The electrolytes of the blood and urine, plasma angiotensin, plasma renin activity, and plasma aldosterone were analyzed at the central chemistry laboratory of Tongde Hospital of Shanxi province. Besides, ECG, chest X-ray, bone mineral density (BMD) examination and ultrasound examination were conducted.

The diagnosis of Gitelman syndrome was based on the clinical symptoms, biochemical measurements and analysis of genetic mutations of SLC12A3 gene. Genomic DNA was extracted from peripheral blood samples of the female patient using a nucleic acid extraction kit (NO. BST01051, BaiO Technology Co., Ltd, Shanghai, China) according to the manufacturers protocol. The SLC12A3 gene was screened for mutations using Sanger sequencing. The nucleotide sequences of the PCR products were aligned to the UCSC database using SnapGee software (v3.2.1)

Blood pressure, heart rate, and body mass index (BMI) of the patient were 128/70 mmHg, 76 beats per minute, and 26.7 kg/m2, respectively. Systemic physical examinations showed no abnormalities. The results of laboratory tests of the patient are listed in Table 1. Laboratory assays revealed hypokalemia, hypomagnesemia, hypercalcemia, and metabolic alkalosis. Furthermore, the patient had elevated parathyroid hormone (PTH) and plasma renin activity and angiotensin II. 24-h urine analysis showed that the levels of urinary potassium and urinary calcium were normal. ECG revealed normal sinus rhythm, ST segment and T-waves abnormality but had no prolongation of the QT interval. The BMD data showed there was a significant decrease at the left forearm. Chest X-ray and ultrasound (thyroid, carotid, heart, abdomen, and pelvic cavity) did not show any obvious abnormalities (data not shown).

Table 1 Laboratory Tests of the Subject

Sanger sequencing of SLC12A3 gene was performed in the subject. Genetic analysis showed 4 mutations in the exons of SLC12A3 gene: c.366A > G in exon 2, c.791C > G in exon 6, c.1027C > T in exon 8, and c1456G>A in exon 12 (Figure 1).

Figure 1 Genetic analysis of the SLC12A3 gene. (A) c.366A > G in Exon 2. (B) c.791C > G in Exon 6. (C) c.1027C > T in Exon 8 and (D) c.1456 G > A in Exon 12. The mutant nucleotides are marked in the red frames.

After the diagnosis, spironolactone and potassium citrate were used to treat hypokalemia and potassium magnesium aspartate was used to treat hypomagnesaemia. The patient was discharged with normokalemia and no other discomfort following one week of treatment.

In the present study, we reported the case of a 60-year-old Chinese female patient with GS. The biochemical examination showed hypokalemia, metabolic alkalosis, hypomagnesemia, hypercalcemia, hyperreninemia, elevated angiotensin II, and PTH levels. ECG showed normal sinus rhythm, ST segment and T-waves abnormality but had no prolongation of the QT interval. Besides, BMD was decreased in the left forearm. Genetic analysis identified four mutations of SLC12A3 gene, c.366A > G in exon 2, c.791C > G in exon 6, c.1027C > T in exon 7, and c1456G>A in exon 12. The treatment with supplements of potassium and magnesium improved hypokalemia and hypomagnesemia.

GS is a rare inherited salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia, hypocalciuria and RAAS activation. GS is caused by mutations in SLC12A3 gene coding for the thiazide-sensitive NCCT of the DCT, which leads to a decrease in sodium reabsorption, increases potassium and hydrogen excretion and therefore develop hypokalemic metabolic alkalosis.14 The enhanced passive Ca2+ transport in the proximal tubule leads to hypocalciuria15 and the downregulation of the epithelial Mg2+ channel transient receptor potential channel subfamily M, member 6 (Trpm6) is a possible mechanism involved in hypomagnesemia.16 The mechanism of hypocalciuria is uncertain, but some studies have found that one reason for it may be hypovolemia. Meanwhile, hypovolemia activates RAAS.17,18 The patient had hypokalemia, metabolic alkalosis, hypomagnesemia, hyperreninemia, and elevated angiotensin II level, which was consistent with the clinical manifestations of GS. In the study, the elderly female had decreased BMD. Postmenopausal women are prone to develop hypocalcemia and postmenopausal osteoporosis, which is caused by estrogen deficiency after menopause. Long-term hypocalcemia may overstimulate the parathyroid gland and lead to secondary hyperparathyroidism.

Genetic identification is the golden standard for the diagnosis of GS. We identified compound mutations of SLC12A3, c.366A > G in exon 2, c.791C > G in exon 6, c.1027C > T in exon 7, and c1456G>A in exon 12. The c1456G>A in exon 12 is reported as a hotspot mutation of SLC12A3. A heterozygous mutation, c.366A > G in the gene has been reported. But c.366A > G in exon 2 was a homozygous mutation in this study. Moreover, c.791C > G and c.1027C > T are two novel mutations. Hence, we performed a complementary study on the mutations of SLC12A3.

GS and Bartter syndrome (BS) show extremely similar clinical and laboratory manifestations including hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronemia. But BS presents with an early age of onset and exhibits apparent clinical symptoms.12 Simultaneously, BS is closely related to the mutations of CLCNKB gene. They can be differentiated by clinical manifestation and genetic tests.19,20

Our present study has several limitations. First, the mutation was detected in only one patient but not in pedigree. Further research should be performed in the pedigree. Second, a further exploration is needed to find the correlation between genotype and phenotype and then provide better understanding of GS. Moreover, more experiments are needed to reveal the underlying molecular mechanism of GS.

Overall, our study identified four mutations of SLC12A3 gene in a Chinese female patient and three of the mutations were novel. These findings might be useful for better understanding the function of this gene and aid with diagnosis and treatment decisions.

The study was conducted in compliance with the Declaration of Helsinki. The protocol was approved by the Ethics Committee of Tongde Hospital of Shanxi province. The patient provided informed consent for the case details to be published.

All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

This work was supported by grants from the Chinese National Natural Science Foundation [No. 81560044, No. 30860113], the Appropriate Technology for Medical Health Research and Development Projects of Guangxi [S201422-01] and Health Research Project of Shanxi [2019165].

The authors declare that they have no competing interests.

1. Gitelman HJ, Graham JB, Welt LG. A new familial disorder characterized by hypokalemia and hypomagnesemia. Trans Assoc Am Phys. 1966;79:221235.

2. Knoers NV, Levtchenko EN. Gitelman Syndrome. Orphanet J Rare Dis. 2008;3:22. doi:10.1186/1750-1172-3-22

3. Mastroianni N, Bettinelli A, Bianchetti M, et al. Novel molecular variants of the Na-cl cotransporter gene are responsible for Gitelman syndrome. Am J Hum Genet. 1996;59(5):10191026.

4. Glaudemans B, Yntema HG, San-Cristobal P, et al. Novel NCC mutants and functional analysis in a new cohort of patients with Gitelman syndrome. Eur J Hum Genet. 2012;20:263270. doi:10.1038/ejhg.2011.189

5. Ma J, Ren H, Lin L, et al. Genetic features of Chinese patients with Gitelman syndrome: sixteen novel SLC12A3 mutations identified in a new cohort. Am J Nephrol. 2016;44:113121. doi:10.1159/000447366

6. Gug C, Mihaescu A, Mozos I. Two mutations in the thiazide sensitive NaCl co-transporter gene in a Romanian Gitelman syndrome patient: case report. Ther Clin Risk Manag. 2018;14:149155. doi:10.2147/TCRM.S150483

7. Vargas-Poussou R, Dahan K, Kahila D, et al. Spectrum of mutations in Gitelman syndrome. J Am Soc Nephrol. 2011;22:693703. doi:10.1681/ASN.2010090907

8. Reissinger A, Ludwig M, Utsch B, et al. Novel NCCT gene mutations as a cause of Gitelmans syndrome and a systematic review of mutant and polymorphic NCCT alleles. Kidney Blood Press Res. 2002;25(6):354362. doi:10.1159/000068695

9. Lu Q, Zhang Y, Song C, et al. A novel SLC12A3 gene homozygous mutation of Gitelman syndrome in an Asian pedigree and literature review. J Endocrinol Investig. 2016;39(3):333340. doi:10.1007/s40618-015-0371-y

10. Munoz EV, Chang Q, Bindels RJ, et al. Gitelman syndrome: towards genotypephenotype correlations. Pediatr Nephrol. 2007;22(3):326332. doi:10.1007/s00467-006-0321-1

11. Fedeli GGC, Cosmai ML, Badalamenti S, et al. Gitelman syndrome: pathophysiological and clinical aspects. Q J Med. 2010;103(10):741748. doi:10.1093/qjmed/hcq123

12. Matsunoshita N, Nozu K, Shono A, et al. Differential diagnosis of Bartter syndrome, Gitelman syndrome, and pseudo-Bartter/Gitelman syndrome based on clinical characteristics. Genet Med. 2016;18(2):180188. doi:10.1038/gim.2015.56

13. Blanchard A, Bockenhauer D, Bolignano D, et al. Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO)controversies conference. Kidney Int. 2017;91:2433. doi:10.1016/j.kint.2016.09.046

14. Gvercin B, Kaynar K, Gler , et al. In the presence of hypokalemia and hypomagnesemia; remember Gitelman syndrome. Hippokratia. 2019;23.

15. Reilly RF, Huang CL. The mechanism of hypocalciuria with NaCl cotransporter inhibition. Nat Rev Nephrol. 2011;7:669674. doi:10.1038/nrneph.2011.138

16. Shahzad MA, Mukhtar M, Ahmed A, et al. Gitelman Syndrome: a rare cause of seizure disorder and a systematic review. Case Rep Med. 2019;2019:4204907. doi:10.1155/2019/4204907

17. Tseng MH, Yang SS, Hsu YJ, et al. Genotype, phenotype, and follow-up in Taiwanese patients with salt-losing tubulopathy associated with SLC12A3 mutation. J Clin Endocrinol Metab. 2012;97(8):E14781482. doi:10.1210/jc.2012-1707

18. Hsu YJ, Yang SS, Cheng CJ, et al. Thiazide-sensitive Na+cl Cotransporter (NCC) gene inactivation results in increased duodenal Ca2+ absorption,enhanced osteoblast differentiation and elevated bone mineral density. J Bone Miner Res. 2015;30(1):116127. doi:10.1002/jbmr.2306

19. Simon DB, Karet FE, Hamdan JM, et al. Bartters syndrome, hypokalaemic alkalosis with hypercalciuria, is caused by mutations in the Na-K-2Cl cotransporter NKCC2. Nat Genet. 1996;13(2):183188. doi:10.1038/ng0696-183

20. Shaer AJ. Inherited primary renal tubular hypokalemic alkalosis: a review of Gitelman and Bartter syndromes. Am J Med Sci. 2001;322(6):316332. doi:10.1097/00000441-200112000-00004

See original here:
Homozygous Mutations of SLC12A3 gene in Gitelman Syndrome | IJGM - Dove Medical Press

Diet advice changes with the decades. I remember eating cheeseless pizzas during the "fat-free" fad (thanks, Dad). And I'll never forget my high school cross country team's T-shirts saying "Eat Pasta, Run Fasta."

If we've learned anything from these fads, it isn't how to eat better. It is that there is no one-size-fits-all diet.

Now, a growing field called "nutrigenomics" aims to provide people with personalized lifestyle guidance, based on their DNA. But is this a breakthrough for nutrition science, or just another fad?

Melina Jampolis is a board-certified physician and nutrition specialist. She helps people reach their goals for fitness and body composition by giving tailor-made diet recommendations.

"Nutrition is all about context. We don't eat nutrients, we eat foods."

A few years ago, a 32-year-old vegetarian man came to her seeking advice on how to build muscle and burn fat.

After four months without progress, Jampolis suggested a Nutrigenomix test. Nutrigenomix is one of several dozen companies that offer genetic tests that purport to give insight into personalized, gene-based nutrition.

Much like 23andMe or Ancestry.com, by sending salvia to a lab, people can learn more about their genetic makeup. Some of the gene-based nutrition companies accomplish this by interpreting genetic data downloaded from 23andMe or Ancestry.

The analysis a subject receives is intended to help them learn which foods to eat to switch on or off specific genes. It can help them understand what foods might affect weight loss, immune functions, or their predispositions to disease.

Jampolis says the test results "confirmed her clinical intuition." Even though a plant-based diet is a healthy option, vegetarianism wasn't quite right for this man.

According to the test results, her client had a variation in his genetic sequence making it more challenging to build muscle. At the same time, his metabolic panel indicated that he should have fewer carbohydrates. With that combined information, Jampolis recommended that he eat less protein from beans and more animal protein.

For Jampolis, despite some of the companies' claims, the genetic test isn't a magic "how to eat" formula. She says there are many ways to interpret the results, so it is best used with a healthcare professional's guidance.

"As a practitioner, you're taking (a genetic test) in the context of a patient and bringing in multiple variables," she says.

Nutrigenomix is one of the few nutrigenomics tests that must be administered by a medical professional. The founder, Ahmed El-Sohemy, specifically designed it that way to "restore credibility to the field."

El-Sohemy, also the nutrigenomics chair of the University of Toronto, says nutrition can be "vulnerable to snake oil science," and consumers should be cautious about genetic testing.

"It was a bit of a wild west. There were some shady operators (...) linking their tests to ridiculously overpriced supplements that were not justified. It was really tainting the whole field. So, we established a test based on the robust science and decided to make it available only through healthcare professionals so that they can answer questions and concerns that people have around genetic testing."

In 2008, El-Sohemy discovered that some people's genetics could be causing them to eat more sugar regularly than others. He pinpointed the sugar habit to a variation in the GLUT2 gene which became known as the "sweet tooth gene."

But El-Sohemy saw nutrigenomics companies extrapolate new meanings from his work claiming their test for the sweet tooth gene would reveal how a body processes sugar and the optimal sugar intake level.

"That's nonsense. That's not what the study showed," he says, adding other examples of wild claims like genetic tests "for" an anti-inflammatory diet, or low-carb versus low-fat, where "the science just isn't there yet."

Nonetheless, he does believe the field is making progress. When he first launched the Nutrigenomix in 2012, their test only looked at seven genes. By 2018, they were investigating 72.

In the past decade, more rigorous scientific research has been published with discoveries related to nutrigenomics. If "the science isn't there yet," when it comes to crafting personal diets from data, it is on its way.

David Mutch leads a nutrigenomics research program at the University of Guelph, studying diet-gene interactions, especially omega-3 dietary fats. He doesn't work with El-Sohemy but cites his 2006 study on coffee and heart attack risk as a prime example of robust nutrition science.

The study looked at a variant of the gene CYP182, which is associated with how well the body metabolizes caffeine. They found that having a particular version of the gene means that the body metabolizes caffeine slowly, and for this group, excessive coffee consumption may increase their risk of heart attacks.

Studies like this, Mutch says, are building a solid foundation for consumer nutrigenomics tests. If a person tests positive for that gene variant, then the recommendation would be to consume no more than two cups of coffee per day instead of the standard advice of a four-cup limit.

Mutch says that precision nutrition is about much more than DNA. It also takes into account gut bacteria (known as the microbiome), proteins, metabolites, etc. That is why he also supports nutrigenomics tests that are interpreted by a healthcare professional.

"Working with dieticians or healthcare practitioners is actually going to be the most efficient way to take that information you're getting and translate it into an actionable dietary plan. That's the challenge with nutrition. Nutrition is all about context. We don't eat nutrients, we eat foods."

The majority of chronic illnesses in the United States, such as hypertension, high cholesterol, obesity, and diabetes, are treated first with diet and exercise. However, research shows that patients are more likely to adhere to care plans tailored to their genetics instead of general dietary advice.

"This is a piece of the puzzle to better understand ourselves, to better understand what we may or may not want to think about when we're making choices about the foods we're eating or the lifestyle choices we're making," Mutch says.

Maybe someday, to reduce the risk of heart disease, Alzheimer's, or hypertension, doctors will prescribe food as medicine and know their prescription will stand the tests of time and science.

We'd love to hear from you! If you have a comment about this article or if you have a tip for a future Freethink story, please email us at [emailprotected]

More here:
Nutrigenomics Could Be the Future of Eating - Freethink

A clerical error meant that a female polar bear, Tonja, born at Moscow Zoo, was listed as the daughter of the wrong parents, a spokeswoman for Tierpark Berlin told CNN on Wednesday.

Tonja was assigned documents meant for another female polar bear born at Moscow Zoo two days later, but in fact she was the offspring of the same parents as Wolodja, a male polar bear with whom she later mated in Berlin. The pair produced baby Hertha, who was born in December 2018.

Suspicions were raised when documents were found at Moscow Zoo that listed a different birth date for Tonja, and genetic testing has since confirmed she and Wolodja are siblings.

"That was a big shock for us," the spokeswoman said, adding that Moscow Zoo had been very transparent and informed its counterparts in Berlin when the documents were found.

"There was one unfortunate mistake," she said.

The bears are part of the European Endangered Species Programmes (EEP) breeding program for polar bears, which works to maintain the genetic diversity of polar bears in captivity.

Inbreeding reduces genetic diversity, which is "a crucial factor in the long-term survival of species," according to the European Association of Zoos and Aquaria (EAZA).

"This serious mistake is a very regrettable setback for the responsible work of the European Conservation Breeding Programme," Berlin Zoo's director, Andreas Knieriem, said in a statement.

"It must now be a matter of learning from such mistakes and putting our work in all areas even more on a scientific basis."

This kind of mix-up is not likely to happen again, as it is unlikely there will be two breeding pairs at the same zoo, the spokeswoman said. In addition, every animal born at Berlin Zoo is given a microchip containing identifying information, including who its parents are.

In the light of the discovery, neither Tonja nor Hertha will have any offspring for the foreseeable future because their family lineage is better represented in the captive polar bear population than previously thought, the spokeswoman said.

However, there is a chance that both bears will be bred in the future, she added.

"Our mission is to keep the genetic diversity as big as possible," said the spokeswoman.

Hertha is a "happy and healthy bear" who will remain at the zoo along with her mother, she added. Wolodja has already moved to a different zoo in the Netherlands.

Polar bears are listed as vulnerable by the International Union for Conservation of Nature (IUCN), which estimates that there are 22,000-31,000 left in the wild.

UK campaign organization Bear Conservation estimates that there are more than 300 polar bears in captivity around the world.

Read more from the original source:
Berlin zoo says its polar bear cub's parents were brother and sister - CNN

Potentially clinically actionable genomic alterations were identified in a majority of patients with advanced cancers with next-generation sequencing (NGS), a subcohort of whom showed clinical benefits with targeted treatment directed by the NGS. The results of the prospective study were published in JAMA Oncology.1

In their assessment of the Michigan Oncology Sequencing Program (Mi-ONCOSEQ) cohort study, investigators looked at the use of NGS in 1138 patients with advanced solid tumors, which was successful in 89.2% (n=1015). Of the NGS-successful patients, 817 (80.5%) were discovered to have actionable genomic alterations for treatment, with 132 (16.2%) receiving targeted therapy based on these results. Forty-nine patients had a clinical benefit from the targeted treatment, and responses lasted 12 months or longer in 19.7% of the treated population. These results support the use of directed germline testing in all patients with advanced cancer.

One goal for Mi-ONCOSEQ is to inform standards of practice as clinical sequencing increasingly becomes adopted as a routine standard of care, said Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology and senior author of the study, in an article in the Michigan Health Lab report.2 This study helps demonstrate that the promise of individualized, precision medicine and precision oncology is becoming a reality for patients.

Observed molecular alterations were classified into 3 tiers, depending on the potential for treatment or potential treatment resistance based on the alteration. Tier 1 alterations included those with known clinical utility, germline variants that lead to increased cancer risk, and alterations that mark more or less benefit from an FDA-approved treatment. Tier 2 alterations included alterations that would suggest benefit from investigational or off-label targeted therapy or that would suggest resistance to an FDA-approved therapy. Tier 3 alterations were those without current therapeutic implications.

According to the investigators, 817 patients (80.5%) harbored a potentially actionable tier 1 or 2 alteration, 288 patients had tier 1 alterations, and 744 had tier 2 alterations. Among these alterations, 962 (94.8%) were identified by DNA sequencing and 645 (63.5%) by RNA sequencing. In 579 cases (57.0%), all 3 modes of integrated sequencing and analysis found informative alterations for potential treatment.

Sequencing-directed therapy (SDT) was started in 132 of the 817 patients (16.2%) with potentially clinically actionable alterations, with the median time to enrollment in the treatment being 3.8 months (range, 0.2-44.0). Seventy-four patients were enrolled and treated in a clinical trial, 43 were treated with off-label therapy, and 15 were treated with on-label therapy. Forty-nine patients (37.1%) experienced clinical benefit after being matched with treatment, with the most common cancers treated being sarcoma (12 of 138 [8.7%]) and prostate adenocarcinoma (10 of 154 [6.5%]).

Treatments for patients receiving SDT included targeted CDK4/6 inhibitors (n=21), PARP inhibitors (n =16), and FGFR inhibitors (n =11). The most common treatment received was immune checkpoint inhibitors, in 29 patients. The 26 patients who were deemed to have an exceptional response to SDT had a response duration ranging from 12.1 to 39.5 months. Ten of the patients had DNA repair defects, 5 of whom had double-strand DNA repair defects, including BRCA1, BRCA2, ATM, PALB2, and BRIP1.

Any family members who have also inherited those same mutations may be at increased risk for cancer, added Erin F. Cobain, MD, a coauthor in the study and a clinical lecturer and oncologist at Michigan Medicine, in a statement.2 So a lot of this testing prompted downstream genetic testing and counseling across families. Thats how sequencing can have even more far-reaching impact than just looking for therapies to directly help a current patient.

Several factors accounted for NGS testing not being successful in some patients, including the inability to safely test, patients withdrawal due to entering hospice, and inadequate tumor content from the biopsy. The average age of patients who enrolled was 57 years; 53% were men. Prior to enrollment, 855 patients had received systemic therapy and an average of 47 months had elapsed between the time of the patients diagnosis and their enrollment in the study.

Based on the data presented by Cobain and others, it is evident that such precision medicine strategies are especially fruitful in cancer types without clear standard-of-care options, such as carcinoma of unknown primary and other rare tumors, investigators wrote in an editorial accompanying the study, discussing the benefits of NGS for patients with rare cancers.3

NGS remains a challenge for oncologists for several reasons, among them that the definition of clinically actionable alterations changes as new therapies emerge and that a patients tumors can harbor multiple mutations. According to the investigators, more novel clinical trials need to be explored to expand treatment. However, systems also must develop large-scale precision oncology studies to continue to find ways to match patients with targeted treatments.

Our data support a recommendation for germline testing of DNA repair genes as standard practice in patients with metastatic solid tumors and comprehensive NGS profiling at diagnosis for patients with [cancer of unknown primary], the study authors concluded.1 With continued discovery of genomic biomarkers predictive of clinical benefit from anticancer therapies, we anticipate even broader clinical applicability of this technology.

References:

1. Cobain EF, Wu YM, Vats P, et al. Assessment of clinical benefit of integrative genomic profiling in advanced solid tumors. JAMA Oncol. 2021;7(4):525-533. doi:10.1001/jamaoncol.2020.7987

2. Demsky I. How useful is next-generation sequencing for patients with advanced cancer? Michigan Health Lab. March 11, 2021. Accessed March 23, 2021. https://bit.ly/3cjajLT

3. Yap TA, Johnson A, Meric-Bernstam F. Precision medicine in oncologytoward the integrated targeting of somatic and germline genomic aberrations. JAMA Oncol. 2021;7(4):507-509. doi:10.1001/jamaoncol.2020.7988

See the article here:
Large NGS Trial Identifies Actionable Alterations in Most Patients With Advanced Cancers - Targeted Oncology

This has brought along several changes in This report also covers the impact of COVID-19 on the global market.

The Breast Cancer Predictive Genetic Testing Market analysis summary by Reports Insights is a thorough study of the current trends leading to this vertical trend in various regions. In addition, this study emphasizes thorough competition analysis on market prospects, especially growth strategies that market experts claim.

Breast Cancer Predictive Genetic Testing Market competition by top manufacturers as follow: OncoCyte Corporation, Cancer Genetics, Myriad Genetics, Iverson Genetics, NeoGenomics, Roche, Quest Diagnostics, PerkinElmer, Invitae, Thermo Fisher Scientific

Get a Sample PDF copy of the report @ https://www.reportsinsights.com/sample/415404

The global Breast Cancer Predictive Genetic Testing market has been segmented on the basis of technology, product type, application, distribution channel, end-user, and industry vertical, along with the geography, delivering valuable insights.

The Type Coverage in the Market are: High Penetrant GenesIntermediate Penetrant GenesLow Penetrant Genes

Market Segment by Applications, covers:

HospitalsClinicsOther

Market Segment as follows:By RegionAsia-Pacific[China, Southeast Asia, India, Japan, Korea, Western Asia]Europe[Germany, UK, France, Italy, Russia, Spain, Netherlands, Turkey, Switzerland]North America[United States, Canada, Mexico]Middle East & Africa[GCC, North Africa, South Africa]South America[Brazil, Argentina, Columbia, Chile, Peru]

The research provides answers to the following key questions: What is the estimated growth rate and market share and size of the Breast Cancer Predictive Genetic Testing market for the forecast period 2021 2028? What are the driving forces in the Breast Cancer Predictive Genetic Testing market for the forecast period 2021 2028? Who are the prominent market players and how have they gained a competitive edge over other competitors? What are the market trends influencing the progress of the Breast Cancer Predictive Genetic Testing industry worldwide? What are the major challenges and threats restricting the progress of the industry? What opportunities does the market hold for the prominent market players?

For any other requirements, please feel free to contact us and we will provide you customized report.

Market segment by Regions/Countries, this report coversNorth AmericaEuropeChinaRest of Asia PacificCentral & South AmericaMiddle East & Africa

Major factors covered in the report:

To get this report at a profitable rate.: https://www.reportsinsights.com/discount/415404

The analysis objectives of the report are:

Our report offers:

Market share assessments for the regional and country level segments. Market share analysis of the top industry players. Strategic recommendations for the new entrants. Market forecasts for a minimum of 9 years of all the mentioned segments, sub segments and the regional markets. Market Trends (Drivers, Constraints, Opportunities, Threats, Challenges, Investment Opportunities, and recommendations). Strategic recommendations in key business segments based on the market estimations. Competitive landscaping mapping the key common trends. Company profiling with detailed strategies, financials, and recent developments. Supply chain trends mapping the latest technological advancements.

Access full Report Description, TOC, Table of Figure, Chart, etc. @ https://www.reportsinsights.com/industry-forecast/Breast-Cancer-Predictive-Genetic-Testing-Market-415404

About US:

ReportsInsights is the leading research industry that offers contextual and data-centric research services to its customers across the globe. The firm assists its clients to strategize business policies and accomplish sustainable growth in their respective market domain. The industry provides consulting services, syndicated research reports, and customized research reports.

Contact US:

Email:[emailprotected]

Sales:[emailprotected]

Read more:
Breast Cancer Predictive Genetic Testing Market 2021 In-Depth Insights and Business Scenario, Analysis by 2028 Brockville Observer - Brockville...

Orphan: First Kill star Julia Stiles has teased another big twist in the upcoming horror prequel, one which may even rival the first movie's shocking finale. Many had wondered how, what with Orphan: First Kill taking place before the first movie and after audiences have been made aware of Esther's surprising identity, the prequel would bring the shocks and scares, but according to Stiles they have found a way.

Released in 2009, the first Orphan centers on a couple who, after the death of their unborn child, adopt a mysterious nine-year-old girl, Esther. As she demonstrates increasingly bizarre behaviour, it is revealed during the movie's climax that Esther is in fact an adult woman with hypopituitarism, a rare hormonal disorder that stunted her physical growth and caused proportional dwarfism.

While it remains unknown how exactly Orphan: First Kill will pull out a twist to rival the first movie, Stiles goes on to assure fans that the prequel will continue to opt for psychological scares rather than blood and gore.

Orphan: First Kill will once again follow Isabelle Fuhrman as Esther, who is now living under the name Leena Klammer. The horror begins when she orchestrates a brilliant escape from an Estonian psychiatric facility and travels to America by impersonating the missing daughter of a wealthy family. But Leena's new life as 'Esther' comes with an unexpected wrinkle and pits her against a mother who will protect her family at any cost.

Fuhrman, who is now 24 years old, will once again play the role of the adult killer who disguises herself as a child, with director William Brent Bell recently providing some insight into how the movie plans to resurrect Esther all these years later. "For me it's like, we know the secret of the first film, so the fun of bringing Isabelle Fuhrman back into the role - which was a whole process to get approved - that is a challenge in and of itself," the filmmaker said. "And likewise, not doing modern CGI... I mean, we use digital, we use CGI to help us... but not to create her at all. It's all old school techniques: forced perspective, camera angles, where we put the light."

Orphan: First Kill does not yet have a release date. This comes to us from Collider.

Topics: Orphan 2

Read more from the original source:
Orphan: First Kill Has a Surprise Twist That Could Rival the Original's Shocking Ending - MovieWeb

News and research before you hear about it on CNBC and others. Claim your 1-week free trial to StreetInsider Premium here.

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of KEYTRUDA, Mercks anti-PD-1 therapy, in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the esophagus or human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 (Combined Positive Score [CPS] 10). The CHMPs recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the second quarter of 2021.

Patients with metastatic esophageal cancer currently face five-year survival rates of just 5%, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. There is a critical need for new treatment options in the first-line setting that can potentially extend their lives. Todays positive opinion for KEYTRUDA is an important step forward for patients in Europe with certain types of gastrointestinal cancers.

The positive CHMP opinion is based on results from the pivotal Phase 3 KEYNOTE-590 trial, in which KEYTRUDA plus 5-fluorouracil (5-FU) and cisplatin demonstrated significant improvements in overall survival and progression-free survival compared with 5-FU and cisplatin alone in patients regardless of histology or PD-L1 expression status. KEYTRUDA plus 5-FU and cisplatin reduced the risk of death by 27% (HR=0.73 [95% CI, 0.62-0.86]; p

Merck is studying KEYTRUDA across multiple settings and stages of gastrointestinal cancer including esophageal, gastric, hepatobiliary, pancreatic, colorectal and anal cancers through its broad clinical program.

About Esophageal Cancer

Esophageal cancer begins in the inner layer (mucosa) of the esophagus and grows outward. Esophageal cancer is the eighth most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. Globally, it is estimated there were more than 604,000 new cases of esophageal cancer diagnosed and approximately 544,000 deaths resulting from the disease in 2020. In Europe, it is estimated there were more than 52,000 new cases of esophageal cancer diagnosed and approximately 45,000 deaths resulting from the disease in 2020.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,400 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS 10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Carcinoma

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after 2 or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% of these patients interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen, which was at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatment. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

See more here:
Merck (MRK) Granted Positive EU CHMP Opinion for KEYTRUDA (pembrolizumab) in Combination with Chemotherapy - StreetInsider.com

Get instant alerts when news breaks on your stocks. Claim your 1-week free trial to StreetInsider Premium here.

Data evaluating Opdivo plus Yervoy represent the longest reported median overall survival from a Phase 3 advanced melanoma trial

49% of patients treated with Opdivo plus Yervoy were alive at 6.5 years and 77% of these patients remained treatment-free

Data to be featured in an oral presentation during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE: BMY) today announced new six-and-a-half-year data from CheckMate -067, a randomized, double-blind, Phase 3 clinical trial, demonstrating durable improvement in survival with first-line Opdivo (nivolumab) plus Yervoy (ipilimumab) therapy and Opdivo monotherapy, versus Yervoy alone, in patients with advanced melanoma. With a minimum follow-up of 6.5 years, median overall survival (OS) was 72.1 months with Opdivo plus Yervoy (95% CI: 38.2-NR), the longest reported median OS in a Phase 3 advanced melanoma trial, 36.9 months with Opdivo (95% CI: 28.2-58.7) and 19.9 months with the Yervoy group (95% CI: 16.8-24.6). In addition, the Opdivo plus Yervoy combination demonstrated a 6.5-year progression-free survival (PFS) rate of 34% (median of 11.5 months) while PFS rates were 29% (median of 6.9 months) and 7% (median of 2.9 months) for Opdivo alone and Yervoy alone, respectively. Of the 49% of patients alive and in follow-up, 77% of patients who received the combination (112/145), 69% of Opdivo-treated patients (84/122) and 43% (27/63) of Yervoy-treated patients have been off treatment and never received subsequent systemic therapy.

Durable, sustained clinical benefit was also observed with Opdivo plus Yervoy or Opdivo alone across relevant subgroups, including in patients with BRAF mutation, wild-type tumors, and baseline liver metastases. Among patients with BRAF-mutant tumors, the rate of OS at 6.5 years was 57% in patients who received Opdivo plus Yervoy, 43% for Opdivo alone, and 25% for Yervoy alone. In patients with BRAF wild-type tumors, the rate of OS was 46% in patients who received Opdivo plus Yervoy, 42% for Opdivo alone and 22% for Yervoy alone. The rate of OS among patients with liver metastases was 38% for those who received Opdivo plus Yervoy, 31% for Opdivo alone, and 22% for Yervoy alone. Median duration of response (DoR) was not reached for those who received Opdivo plus Yervoy nor Opdivo, while the DoR for Yervoy-treated patients was 19.2 months.

The sustained overall survival and progression-free survival benefit shown with nivolumab-based treatment, particularly the nivolumab plus ipilimumab combination, has changed the way we look at long-term efficacy outcomes for patients with advanced melanoma, said Jedd D. Wolchok, M.D., Ph.D., FASCO, Chief, Immuno-Oncology Service, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center. These new results from the CheckMate -067 trial, with nearly half of patients treated with the nivolumab and ipilimumab combination surviving to six-and-a-half years, confirm the durable, sustained benefit of the combination in patients with advanced melanoma.

The safety profile for Opdivo plus Yervoy was consistent with prior findings, with no new safety signals observed and no additional treatment-related deaths occurring since the five-year analysis. Grade 3/4 treatment-related adverse events were reported in 59% of patients in the combination group, 24% of patients in the Opdivo group, and 28% of patients in the Yervoy group.

These results build upon our decade-long legacy in treating melanoma, which began when the average life expectancy following a diagnosis of metastatic melanoma was roughly six months and less than 10% of patients survived beyond five years, said Gina Fusaro, development lead, melanoma, Bristol Myers Squibb. With some of the longest follow-up with immunotherapies to date, Opdivo and Yervoy have consistently demonstrated durable, long-term survival benefits for patients diagnosed with advanced melanoma.

Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -067 clinical trial. The 6.5-year CheckMate -067 data (Abstract #9506) will be presented in an oral abstract session on Sunday, June 6, 2021 from 8:00 a.m. to 11:00 a.m. EDT at the American Society of Clinical Oncology (ASCO) Annual Meeting 2021 from June 4-8.

Dr. Wolchok has provided consulting services to Bristol Myers Squibb.

About CheckMate -067

CheckMate -067 is a Phase 3, double-blind, randomized trial that evaluated the combination of Opdivo plus Yervoy or Opdivo monotherapy versus Yervoy monotherapy in 945 patients with previously untreated advanced melanoma. Patients in the combination group (n=314) received Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks (Q3W) for four doses followed by Opdivo 3 mg/kg every two weeks (Q2W). Patients in the Opdivo monotherapy group (n=316) received Opdivo 3 mg/kg Q2W plus placebo. Patients in the Yervoy monotherapy group (n=315) received Yervoy 3 mg/kg Q3W for four doses plus placebo. Patients were treated until progression or unacceptable toxic effects. Overall survival (OS) and progression-free survival (PFS) were dual endpoints of the trial. Secondary endpoints included objective response rates (ORR), descriptive efficacy assessments and safety.

About Melanoma

Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the United States, 106,110 new diagnoses of melanoma and about 7,180 related deaths are estimated for 2021. Globally, the World Health Organization estimates that by 2035, melanoma incidence will reach 424,102, with 94,308 related deaths. Melanoma is mostly curable when treated in its very early stages; however, survival rates decrease if regional lymph nodes are involved.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision transforming patients lives through science. The goal of the companys cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patients life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the bodys own immune system to help restore anti-tumor immune response. By harnessing the bodys own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivos leading global development program is based on Bristol Myers Squibbs scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has treated more than 35,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 65 countries, including the United States, the European Union, Japan and China. In October 2015, the Companys Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

INDICATIONS

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 (1%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab) and 2 cycles of platinum-doublet chemotherapy, is indicated for the first-line treatment of adult patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

OPDIVO (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the first-line treatment of patients with intermediate or poor risk advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab), in combination with cabozantinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

OPDIVO (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), as a single agent, is indicated for the treatment of adult and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab), in combination with YERVOY (ipilimumab), is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO (nivolumab) is indicated for the treatment of patients with unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC) after prior fluoropyrimidine- and platinum-based chemotherapy.

OPDIVO (nivolumab), in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions listed herein may not include all possible severe and fatal immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. While immune-mediated adverse reactions usually manifest during treatment, they can also occur after discontinuation of OPDIVO or YERVOY. Early identification and management are essential to ensure safe use of OPDIVO and YERVOY. Monitor for signs and symptoms that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and periodically during treatment with OPDIVO and before each dose of YERVOY. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). In general, if OPDIVO or YERVOY interruption or discontinuation is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.

Immune-Mediated Pneumonitis

OPDIVO and YERVOY can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients receiving OPDIVO monotherapy, immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients, including Grade 4 (

In Checkmate 205 and 039, pneumonitis, including interstitial lung disease, occurred in 6.0% (16/266) of patients receiving OPDIVO. Immune-mediated pneumonitis occurred in 4.9% (13/266) of patients receiving OPDIVO, including Grade 3 (n=1) and Grade 2 (n=12).

Immune-Mediated Colitis

OPDIVO and YERVOY can cause immune-mediated colitis, which may be fatal. A common symptom included in the definition of colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. In patients receiving OPDIVO monotherapy, immune-mediated colitis occurred in 2.9% (58/1994) of patients, including Grade 3 (1.7%) and Grade 2 (1%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated colitis occurred in 25% (115/456) of patients, including Grade 4 (0.4%), Grade 3 (14%) and Grade 2 (8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated colitis occurred in 9% (60/666) of patients, including Grade 3 (4.4%) and Grade 2 (3.7%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated colitis occurred in 12% (62/511) of patients, including Grade 3-5 (7%) and Grade 2 (5%).

Immune-Mediated Hepatitis and Hepatotoxicity

OPDIVO and YERVOY can cause immune-mediated hepatitis. In patients receiving OPDIVO monotherapy, immune-mediated hepatitis occurred in 1.8% (35/1994) of patients, including Grade 4 (0.2%), Grade 3 (1.3%), and Grade 2 (0.4%). In patients receiving OPDIVO monotherapy in Checkmate 040, immune-mediated hepatitis requiring systemic corticosteroids occurred in 5% (8/154) of patients. In patients receiving OPDIVO 1 mg/ kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 15% (70/456) of patients, including Grade 4 (2.4%), Grade 3 (11%), and Grade 2 (1.8%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), Grade 3 (4.9%), and Grade 2 (0.4%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated hepatitis occurred in 4.1% (21/511) of patients, including Grade 3-5 (1.6%) and Grade 2 (2.5%).

OPDIVO in combination with cabozantinib can cause hepatic toxicity with higher frequencies of Grade 3 and 4 ALT and AST elevations compared to OPDIVO alone. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. In patients receiving OPDIVO and cabozantinib, Grades 3 and 4 increased ALT or AST were seen in 11% of patients.

Immune-Mediated Endocrinopathies

OPDIVO and YERVOY can cause primary or secondary adrenal insufficiency, immune-mediated hypophysitis, immune-mediated thyroid disorders, and Type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Withhold OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism; initiate hormone replacement as clinically indicated. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism; initiate hormone replacement or medical management as clinically indicated. Monitor patients for hyperglycemia or other signs and symptoms of diabetes; initiate treatment with insulin as clinically indicated.

In patients receiving OPDIVO monotherapy, adrenal insufficiency occurred in 1% (20/1994), including Grade 3 (0.4%) and Grade 2 (0.6%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, adrenal insufficiency occurred in 8% (35/456), including Grade 4 (0.2%), Grade 3 (2.4%), and Grade 2 (4.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, adrenal insufficiency occurred in 7% (48/666) of patients, including Grade 4 (0.3%), Grade 3 (2.5%), and Grade 2 (4.1%). In patients receiving OPDIVO and cabozantinib, adrenal insufficiency occurred in 4.7% (15/320) of patients, including Grade 3 (2.2%) and Grade 2 (1.9%).

In patients receiving OPDIVO monotherapy, hypophysitis occurred in 0.6% (12/1994) of patients, including Grade 3 (0.2%) and Grade 2 (0.3%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypophysitis occurred in 9% (42/456), including Grade 3 (2.4%) and Grade 2 (6%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypophysitis occurred in 4.4% (29/666) of patients, including Grade 4 (0.3%), Grade 3 (2.4%), and Grade 2 (0.9%).

In patients receiving OPDIVO monotherapy, thyroiditis occurred in 0.6% (12/1994) of patients, including Grade 2 (0.2%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, thyroiditis occurred in 2.7% (22/666) of patients, including Grade 3 (4.5%) and Grade 2 (2.2%).

In patients receiving OPDIVO monotherapy, hyperthyroidism occurred in 2.7% (54/1994) of patients, including Grade 3 (

In patients receiving OPDIVO monotherapy, hypothyroidism occurred in 8% (163/1994) of patients, including Grade 3 (0.2%) and Grade 2 (4.8%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, hypothyroidism occurred in 20% (91/456) of patients, including Grade 3 (0.4%) and Grade 2 (11%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, hypothyroidism occurred in 18% (122/666) of patients, including Grade 3 (0.6%) and Grade 2 (11%).

In patients receiving OPDIVO monotherapy, diabetes occurred in 0.9% (17/1994) of patients, including Grade 3 (0.4%) and Grade 2 (0.3%), and 2 cases of diabetic ketoacidosis. In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, diabetes occurred in 2.7% (15/666) of patients, including Grade 4 (0.6%), Grade 3 (0.3%), and Grade 2 (0.9%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, Grade 2-5 immune-mediated endocrinopathies occurred in 4% (21/511) of patients. Severe to life-threatening (Grade 3-4) endocrinopathies occurred in 9 (1.8%) patients. All 9 patients had hypopituitarism, and some had additional concomitant endocrinopathies such as adrenal insufficiency, hypogonadism, and hypothyroidism. Six of the 9 patients were hospitalized for severe endocrinopathies. Moderate (Grade 2) endocrinopathy occurred in 12 patients (2.3%), including hypothyroidism, adrenal insufficiency, hypopituitarism, hyperthyroidism and Cushings syndrome.

Immune-Mediated Nephritis with Renal Dysfunction

OPDIVO and YERVOY can cause immune-mediated nephritis. In patients receiving OPDIVO monotherapy, immune-mediated nephritis and renal dysfunction occurred in 1.2% (23/1994) of patients, including Grade 4 (

Immune-Mediated Dermatologic Adverse Reactions

OPDIVO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes.

YERVOY can cause immune-mediated rash or dermatitis, including bullous and exfoliative dermatitis, SJS, TEN, and DRESS. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/ exfoliative rashes.

Withhold or permanently discontinue OPDIVO and YERVOY depending on severity (please see section 2 Dosage and Administration in the accompanying Full Prescribing Information).

In patients receiving OPDIVO monotherapy, immune-mediated rash occurred in 9% (171/1994) of patients, including Grade 3 (1.1%) and Grade 2 (2.2%). In patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, immune-mediated rash occurred in 28% (127/456) of patients, including Grade 3 (4.8%) and Grade 2 (10%). In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated rash occurred in 16% (108/666) of patients, including Grade 3 (3.5%) and Grade 2 (4.2%).

In a separate Phase 3 trial of YERVOY 3 mg/kg monotherapy, immune-mediated rash occurred in 15% (76/511) of patients, including Grade 3-5 (2.5%) and Grade 2 (12%).

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of

In addition to the immune-mediated adverse reactions listed above, across clinical trials of YERVOY monotherapy or in combination with OPDIVO, the following clinically significant immune-mediated adverse reactions, some with fatal outcome, occurred in

Some ocular IMAR cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Haradalike syndrome, which has been observed in patients receiving OPDIVO and YERVOY, as this may require treatment with systemic corticosteroids to reduce the risk of permanent vision loss.

Infusion-Related Reactions

OPDIVO and YERVOY can cause severe infusion-related reactions. Discontinue OPDIVO and YERVOY in patients with severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Interrupt or slow the rate of infusion in patients with mild (Grade 1) or moderate (Grade 2) infusion-related reactions. In patients receiving OPDIVO monotherapy as a 60-minute infusion, infusion-related reactions occurred in 6.4% (127/1994) of patients. In a separate trial in which patients received OPDIVO monotherapy as a 60-minute infusion or a 30-minute infusion, infusion-related reactions occurred in 2.2% (8/368) and 2.7% (10/369) of patients, respectively. Additionally, 0.5% (2/368) and 1.4% (5/369) of patients, respectively, experienced adverse reactions within 48 hours of infusion that led to dose delay, permanent discontinuation or withholding of OPDIVO. In melanoma patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 2.5% (10/407) of patients. In HCC patients receiving OPDIVO 1 mg/kg with YERVOY 3 mg/kg every 3 weeks, infusion-related reactions occurred in 8% (4/49) of patients. In RCC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg, infusion-related reactions occurred in 5.1% (28/547) of patients. In MSI-H/dMMR mCRC patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, infusion-related reactions occurred in 4.2% (5/119) of patients. In MPM patients receiving OPDIVO 3 mg/kg every 2 weeks with YERVOY 1 mg/kg every 6 weeks, infusion-related reactions occurred in 12% (37/300) of patients.

In separate Phase 3 trials of YERVOY 3 mg/kg and 10 mg/kg monotherapy, infusion-related reactions occurred in 2.9% (28/982) of patients.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with OPDIVO or YERVOY. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between OPDIVO or YERVOY and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with OPDIVO and YERVOY prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, OPDIVO and YERVOY can cause fetal harm when administered to a pregnant woman. The effects of YERVOY are likely to be greater during the second and third trimesters of pregnancy. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with OPDIVO and YERVOY and for at least 5 months after the last dose.

Increased Mortality in Patients with Multiple Myeloma when OPDIVO is Added to a Thalidomide Analogue and Dexamethasone

In randomized clinical trials in patients with multiple myeloma, the addition of OPDIVO to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Lactation

There are no data on the presence of OPDIVO or YERVOY in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 5 months after the last dose.

Serious Adverse Reactions

In Checkmate 037, serious adverse reactions occurred in 41% of patients receiving OPDIVO (n=268). Grade 3 and 4 adverse reactions occurred in 42% of patients receiving OPDIVO. The most frequent Grade 3 and 4 adverse drug reactions reported in 2% to 2%) serious adverse reactions were pneumonia, diarrhea, febrile neutropenia, anemia, acute kidney injury, musculoskeletal pain, dyspnea, pneumonitis, and respiratory failure. Fatal adverse reactions occurred in 7 (2%) patients, and included hepatic toxicity, acute renal failure, sepsis, pneumonitis, diarrhea with hypokalemia, and massive hemoptysis in the setting of thrombocytopenia. In Checkmate 017 and 057, serious adverse reactions occurred in 46% of patients receiving OPDIVO (n=418). The most frequent serious adverse reactions reported in 2% of patients receiving OPDIVO were pneumonia, pulmonary embolism, dyspnea, pyrexia, pleural effusion, pneumonitis, and respiratory failure. In Checkmate 057, fatal adverse reactions occurred; these included events of infection (7 patients, including one case of Pneumocystis jirovecii pneumonia), pulmonary embolism (4 patients), and limbic encephalitis (1 patient). In Checkmate 743, serious adverse reactions occurred in 54% of patients receiving OPDIVO plus YERVOY. The most frequent serious adverse reactions reported in 2% of patients were pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism. Fatal adverse reactions occurred in 4 (1.3%) patients and included pneumonitis, acute heart failure, sepsis, and encephalitis. In Checkmate 214, serious adverse reactions occurred in 59% of patients receiving OPDIVO plus YERVOY (n=547). The most frequent serious adverse reactions reported in 2% of patients were diarrhea, pyrexia, pneumonia, pneumonitis, hypophysitis, acute kidney injury, dyspnea, adrenal insufficiency, and colitis. In Checkmate 9ER, serious adverse reactions occurred in 48% of patients receiving OPDIVO and cabozantinib (n=320). The most frequent serious adverse reactions reported in 2% of patients were diarrhea, pneumonia, pneumonitis, pulmonary embolism, urinary tract infection, and hyponatremia. Fatal intestinal perforations occurred in 3 (0.9%) patients. In Checkmate 025, serious adverse reactions occurred in 47% of patients receiving OPDIVO (n=406). The most frequent serious adverse reactions reported in 2% of patients were acute kidney injury, pleural effusion, pneumonia, diarrhea, and hypercalcemia. In Checkmate 205 and 039, adverse reactions leading to discontinuation occurred in 7% and dose delays due to adverse reactions occurred in 34% of patients (n=266). Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions reported in 1% of patients were pneumonia, infusion-related reaction, pyrexia, colitis or diarrhea, pleural effusion, pneumonitis, and rash. Eleven patients died from causes other than disease progression: 3 from adverse reactions within 30 days of the last OPDIVO dose, 2 from infection 8 to 9 months after completing OPDIVO, and 6 from complications of allogeneic HSCT. In Checkmate 141, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=236). The most frequent serious adverse reactions reported in 2% of patients receiving OPDIVO were pneumonia, dyspnea, respiratory failure, respiratory tract infection, and sepsis. In Checkmate 275, serious adverse reactions occurred in 54% of patients receiving OPDIVO (n=270). The most frequent serious adverse reactions reported in 2% of patients receiving OPDIVO were urinary tract infection, sepsis, diarrhea, small intestine obstruction, and general physical health deterioration. In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY (n=119), serious adverse reactions occurred in 47% of patients. The most frequent serious adverse reactions reported in 2% of patients were colitis/diarrhea, hepatic events, abdominal pain, acute kidney injury, pyrexia, and dehydration. In Checkmate 040, serious adverse reactions occurred in 49% of patients receiving OPDIVO (n=154). The most frequent serious adverse reactions reported in 2% of patients were pyrexia, ascites, back pain, general physical health deterioration, abdominal pain, pneumonia, and anemia. In Checkmate 040, serious adverse reactions occurred in 59% of patients receiving OPDIVO with YERVOY (n=49). Serious adverse reactions reported in 4% of patients were pyrexia, diarrhea, anemia, increased AST, adrenal insufficiency, ascites, esophageal varices hemorrhage, hyponatremia, increased blood bilirubin, and pneumonitis. In Checkmate 238, serious adverse reactions occurred in 18% of patients receiving OPDIVO (n=452). Grade 3 or 4 adverse reactions occurred in 25% of OPDIVO-treated patients (n=452). The most frequent Grade 3 and 4 adverse reactions reported in 2% of OPDIVO-treated patients were diarrhea and increased lipase and amylase. In Attraction-3, serious adverse reactions occurred in 38% of patients receiving OPDIVO (n=209). Serious adverse reactions reported in 2% of patients who received OPDIVO were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia. The following fatal adverse reactions occurred in patients who received OPDIVO: interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%). In Checkmate 649, serious adverse reactions occurred in 52% of patients treated with OPDIVO in combination with chemotherapy (n=782). The most frequent serious adverse reactions reported in 2% of patients treated with OPDIVO in combination with chemotherapy were vomiting (3.7%), pneumonia (3.6%), anemia (3.6%), pyrexia (2.8%), diarrhea (2.7%), febrile neutropenia (2.6%), and pneumonitis (2.4%). Fatal adverse reactions occurred in 16 (2.0%) patients who were treated with OPDIVO in combination with chemotherapy; these included pneumonitis (4 patients), febrile neutropenia (2 patients), stroke (2 patients), gastrointestinal toxicity, intestinal mucositis, septic shock, pneumonia, infection, gastrointestinal bleeding, mesenteric vessel thrombosis, and disseminated intravascular coagulation.

Common Adverse Reactions

In Checkmate 037, the most common adverse reaction (20%) reported with OPDIVO (n=268) was rash (21%). In Checkmate 066, the most common adverse reactions (20%) reported with OPDIVO (n=206) vs dacarbazine (n=205) were fatigue (49% vs 39%), musculoskeletal pain (32% vs 25%), rash (28% vs 12%), and pruritus (23% vs 12%). In Checkmate 067, the most common (20%) adverse reactions in the OPDIVO plus YERVOY arm (n=313) were fatigue (62%), diarrhea (54%), rash (53%), nausea (44%), pyrexia (40%), pruritus (39%), musculoskeletal pain (32%), vomiting (31%), decreased appetite (29%), cough (27%), headache (26%), dyspnea (24%), upper respiratory tract infection (23%), arthralgia (21%), and increased transaminases (25%). In Checkmate 067, the most common (20%) adverse reactions in the OPDIVO arm (n=313) were fatigue (59%), rash (40%), musculoskeletal pain (42%), diarrhea (36%), nausea (30%), cough (28%), pruritus (27%), upper respiratory tract infection (22%), decreased appetite (22%), headache (22%), constipation (21%), arthralgia (21%), and vomiting (20%). In Checkmate 227, the most common (20%) adverse reactions were fatigue (44%), rash (34%), decreased appetite (31%), musculoskeletal pain (27%), diarrhea/colitis (26%), dyspnea (26%), cough (23%), hepatitis (21%), nausea (21%), and pruritus (21%). In Checkmate 9LA, the most common (>20%) adverse reactions were fatigue (49%), musculoskeletal pain (39%), nausea (32%), diarrhea (31%), rash (30%), decreased appetite (28%), constipation (21%), and pruritus (21%). In Checkmate 017 and 057, the most common adverse reactions (20%) in patients receiving OPDIVO (n=418) were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. In Checkmate 743, the most common adverse reactions (20%) in patients receiving OPDIVO plus YERVOY were fatigue (43%), musculoskeletal pain (38%), rash (34%), diarrhea (32%), dyspnea (27%), nausea (24%), decreased appetite (24%), cough (23%), and pruritus (21%). In Checkmate 214, the most common adverse reactions (20%) reported in patients treated with OPDIVO plus YERVOY (n=547) were fatigue (58%), rash (39%), diarrhea (38%), musculoskeletal pain (37%), pruritus (33%), nausea (30%), cough (28%), pyrexia (25%), arthralgia (23%), decreased appetite (21%), dyspnea (20%), and vomiting (20%). In Checkmate 9ER, the most common adverse reactions (20%) in patients receiving OPDIVO and cabozantinib (n=320) were diarrhea (64%), fatigue (51%), hepatotoxicity (44%), palmar-plantar erythrodysaesthesia syndrome (40%), stomatitis (37%), rash (36%), hypertension (36%), hypothyroidism (34%), musculoskeletal pain (33%), decreased appetite (28%), nausea (27%), dysgeusia (24%), abdominal pain (22%), cough (20%) and upper respiratory tract infection (20%). In Checkmate 025, the most common adverse reactions (20%) reported in patients receiving OPDIVO (n=406) vs everolimus (n=397) were fatigue (56% vs 57%), cough (34% vs 38%), nausea (28% vs 29%), rash (28% vs 36%), dyspnea (27% vs 31%), diarrhea (25% vs 32%), constipation (23% vs 18%), decreased appetite (23% vs 30%), back pain (21% vs 16%), and arthralgia (20% vs 14%). In Checkmate 205 and 039, the most common adverse reactions (20%) reported in patients receiving OPDIVO (n=266) were upper respiratory tract infection (44%), fatigue (39%), cough (36%), diarrhea (33%), pyrexia (29%), musculoskeletal pain (26%), rash (24%), nausea (20%) and pruritus (20%). In Checkmate 141, the most common adverse reactions (10%) in patients receiving OPDIVO (n=236) were cough (14%) and dyspnea (14%) at a higher incidence than investigators choice. In Checkmate 275, the most common adverse reactions (20%) reported in patients receiving OPDIVO (n=270) were fatigue (46%), musculoskeletal pain (30%), nausea (22%), and decreased appetite (22%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO as a single agent (n=74), the most common adverse reactions (20%) were fatigue (54%), diarrhea (43%), abdominal pain (34%), nausea (34%), vomiting (28%), musculoskeletal pain (28%), cough (26%), pyrexia (24%), rash (23%), constipation (20%), and upper respiratory tract infection (20%). In Checkmate 142 in MSI-H/dMMR mCRC patients receiving OPDIVO with YERVOY (n=119), the most common adverse reactions (20%) were fatigue (49%), diarrhea (45%), pyrexia (36%), musculoskeletal pain (36%), abdominal pain (30%), pruritus (28%), nausea (26%), rash (25%), decreased appetite (20%), and vomiting (20%). In Checkmate 040, the most common adverse reactions (20%) in patients receiving OPDIVO (n=154) were fatigue (38%), musculoskeletal pain (36%), abdominal pain (34%), pruritus (27%), diarrhea (27%), rash (26%), cough (23%), and decreased appetite (22%). In Checkmate 040, the most common adverse reactions (20%) in patients receiving OPDIVO with YERVOY (n=49), were rash (53%), pruritus (53%), musculoskeletal pain (41%), diarrhea (39%), cough (37%), decreased appetite (35%), fatigue (27%), pyrexia (27%), abdominal pain (22%), headache (22%), nausea (20%), dizziness (20%), hypothyroidism (20%), and weight decreased (20%). In Checkmate 238, the most common adverse reactions (20%) reported in OPDIVO-treated patients (n=452) vs ipilimumab-treated patients (n=453) were fatigue (57% vs 55%), diarrhea (37% vs 55%), rash (35% vs 47%), musculoskeletal pain (32% vs 27%), pruritus (28% vs 37%), headache (23% vs 31%), nausea (23% vs 28%), upper respiratory infection (22% vs 15%), and abdominal pain (21% vs 23%). The most common immune-mediated adverse reactions were rash (16%), diarrhea/colitis (6%), and hepatitis (3%). In Attraction-3, the most common adverse reactions (20%) in OPDIVO-treated patients (n=209) were rash (22%) and decreased appetite (21%). In Checkmate 649, the most common adverse reactions (20%) in patients treated with OPDIVO in combination with chemotherapy (n=782) were peripheral neuropathy (53%), nausea (48%), fatigue (44%), diarrhea (39%), vomiting (31%), decreased appetite (29%), abdominal pain (27%), constipation (25%), and musculoskeletal pain (20%).

In a separate Phase 3 trial of YERVOY 3 mg/kg, the most common adverse reactions (5%) in patients who received YERVOY at 3 mg/kg were fatigue (41%), diarrhea (32%), pruritus (31%), rash (29%), and colitis (8%).

Please see US Full Prescribing Information for OPDIVO and YERVOY.

Clinical Trials and Patient Populations

Checkmate 037previously treated metastatic melanoma; Checkmate 066previously untreated metastatic melanoma; Checkmate 067previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 227previously untreated metastatic non-small cell lung cancer, in combination with YERVOY; Checkmate 9LApreviously untreated recurrent or metastatic non-small cell lung cancer in combination with YERVOY and 2 cycles of platinum-doublet chemotherapy by histology; Checkmate 017second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 743previously untreated unresectable malignant pleural mesothelioma, in combination with YERVOY; Checkmate 214previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 9ERpreviously untreated renal cell carcinoma, in combination with cabozantinib; Checkmate 025previously treated renal cell carcinoma; Checkmate 205/039classical Hodgkin lymphoma; Checkmate 141recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275urothelial carcinoma; Checkmate 142MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040hepatocellular carcinoma, as a single agent or in combination with YERVOY; Checkmate 238adjuvant treatment of melanoma; Attraction-3esophageal squamous cell carcinoma; Checkmate 649previously untreated advanced or metastatic gastric or gastroesophageal junction or esophageal adenocarcinoma.

About the Bristol Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies as single agents and combination regimens for patients with cancer in Japan, South Korea and Taiwan.

About Bristol Myers Squibb

Read the rest here:
Six-and-a-Half-Year Outcomes for Opdivo (nivolumab) in Combination with Yervoy (ipilimumab) Continue to Demonstrate Durable Long-Term Survival...

Opinion Supports Use of KEYTRUDA in Combination With Platinum- and Fluoropyrimidine-Based Chemotherapy in Patients Whose Tumors Express PD-L1 (CPS 10)

Recommendation Based on Significant Survival Benefit Demonstrated With KEYTRUDA Plus Chemotherapy Versus Chemotherapy in Phase 3 KEYNOTE-590 Trial

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending approval of KEYTRUDA, Mercks anti-PD-1 therapy, in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the esophagus or human epidermal growth factor receptor 2 (HER2)-negative gastroesophageal junction (GEJ) adenocarcinoma in adults whose tumors express PD-L1 (Combined Positive Score [CPS] 10). The CHMPs recommendation will now be reviewed by the European Commission for marketing authorization in the European Union, and a final decision is expected in the second quarter of 2021.

Patients with metastatic esophageal cancer currently face five-year survival rates of just 5%, said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. There is a critical need for new treatment options in the first-line setting that can potentially extend their lives. Todays positive opinion for KEYTRUDA is an important step forward for patients in Europe with certain types of gastrointestinal cancers.

The positive CHMP opinion is based on results from the pivotal Phase 3 KEYNOTE-590 trial, in which KEYTRUDA plus 5-fluorouracil (5-FU) and cisplatin demonstrated significant improvements in overall survival and progression-free survival compared with 5-FU and cisplatin alone in patients regardless of histology or PD-L1 expression status. KEYTRUDA plus 5-FU and cisplatin reduced the risk of death by 27% (HR=0.73 [95% CI, 0.62-0.86]; p

Merck is studying KEYTRUDA across multiple settings and stages of gastrointestinal cancer including esophageal, gastric, hepatobiliary, pancreatic, colorectal and anal cancers through its broad clinical program.

About Esophageal Cancer

Esophageal cancer begins in the inner layer (mucosa) of the esophagus and grows outward. Esophageal cancer is the eighth most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. Globally, it is estimated there were more than 604,000 new cases of esophageal cancer diagnosed and approximately 544,000 deaths resulting from the disease in 2020. In Europe, it is estimated there were more than 52,000 new cases of esophageal cancer diagnosed and approximately 45,000 deaths resulting from the disease in 2020.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the bodys immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industrys largest immuno-oncology clinical research program. There are currently more than 1,400 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patients likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (CPS 10), as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

KEYTRUDA is indicated for the first-line treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Carcinoma

KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after 2 or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

Cervical Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Tumor Mutational Burden-High

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation.

Triple-Negative Breast Cancer

KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of antiPD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% of these patients interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 4 (

KEYTRUDA with Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider monitoring more frequently as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased alanine aminotransferase (ALT) (20%) and increased aspartate aminotransferase (AST) (13%) were seen, which was at a higher frequency compared to KEYTRUDA alone. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. In patients with ALT 3 times upper limit of normal (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the 92 patients who were rechallenged with either KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with both (n=55), recurrence of ALT 3 times ULN was observed in 1 patient receiving KEYTRUDA, 16 patients receiving axitinib, and 24 patients receiving both. All patients with a recurrence of ALT 3 ULN subsequently recovered from the event.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA can cause primary or secondary adrenal insufficiency. For Grade 2 or higher, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold KEYTRUDA depending on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of patients receiving KEYTRUDA, including Grade 4 (

Hypophysitis

KEYTRUDA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Hypophysitis occurred in 0.6% (17/2799) of patients receiving KEYTRUDA, including Grade 4 (

Thyroid Disorders

KEYTRUDA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue KEYTRUDA depending on severity. Thyroiditis occurred in 0.6% (16/2799) of patients receiving KEYTRUDA, including Grade 2 (0.3%). None discontinued, but KEYTRUDA was withheld in

Hyperthyroidism occurred in 3.4% (96/2799) of patients receiving KEYTRUDA, including Grade 3 (0.1%) and Grade 2 (0.8%). It led to permanent discontinuation of KEYTRUDA in

Type 1 Diabetes Mellitus (DM), Which Can Present With Diabetic Ketoacidosis

Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold KEYTRUDA depending on severity. Type 1 DM occurred in 0.2% (6/2799) of patients receiving KEYTRUDA. It led to permanent discontinuation in

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 4 (

Immune-Mediated Dermatologic Adverse Reactions

KEYTRUDA can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome, drug rash with eosinophilia and systemic symptoms, and toxic epidermal necrolysis, has occurred with antiPD-1/PD-L1 treatments. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue KEYTRUDA depending on severity. Immune-mediated dermatologic adverse reactions occurred in 1.4% (38/2799) of patients receiving KEYTRUDA, including Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids were required in 40% (15/38) of patients. These reactions led to permanent discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 6% had recurrence. The reactions resolved in 79% of the 38 patients.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barr syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss; Gastrointestinal: Pancreatitis, to include increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis rhabdomyolysis (and associated sequelae, including renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 patients receiving KEYTRUDA. Monitor for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after antiPD-1/PD-L1 treatment. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute and chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between antiPD-1/PD-L1 treatment and allogeneic HSCT. Follow patients closely for evidence of these complications and intervene promptly. Consider the benefit vs risks of using antiPD-1/PD-L1 treatments prior to or after an allogeneic HSCT.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with an antiPD-1/PD-L1 treatment in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

Originally posted here:
Merck Receives Positive EU CHMP Opinion for KEYTRUDA in Combination With Chemotherapy as First-Line Treatment for Certain Patients With Esophageal...

By Sofia MoutinhoMay. 20, 2021 , 11:05 AM

They are no bigger than sesame seeds, and they pulse with a hypnotic rhythm. These are human minihearts, the first to be created in the lab with clearly beating chambers. The miniature organs, or organoids, mimic the working heart of a 25-day-old human embryo and could help unravel many mysteriesincluding why babies hearts dont scar after they experience a heart attack.

This is a great study, says Zhen Ma, a bioengineer who develops heart organoids at Syracuse University and was not part of the new research. The experiment is very important for understanding congenital heart defects and human heart formationwork that has so far relied on animal models, he says.

Although miniorgans like brains, guts, and livers have been grown in dishes for more than 10 years, heart organoids have been more challenging. The first ones, comprised of mouse cardiac cells, could contract rhythmically in a dish, but they looked more like a lump of cardiac cells than a proper heart, says Aitor Aguirre, a stem cell biologist at Michigan State University who has created his own beating human heart organoid, described in a preprint posted to Research Square. An organoid should recapitulate the function of the organ, he says. With a heart, You would expect chambers and pumping, because this is what the heart does.

To create heart organoids whose cells self-organize like those in an embryo, the authors of the new study programmed human pluripotent stem cells, which have the ability to differentiate into any kind of tissue, into various types of cardiac cells. They aimed to create the three tissue layers present in the walls of a heart chamber, one of the first parts of the heart to develop. Next, the researchers immersed the stem cells in different concentrations of growth-promoting nutrients until they found a recipe that coaxed the cells to form tissues in the same order and shape seen in embryos.

After 1 week of development, the organoids are structurally equivalent to the heart of a 25-day-old embryo. At this stage, the heart has only one chamber, which will become the left ventricle of the mature heart. The organoids are about 2 millimeters in diameter and include the main types of cells typically present in this stage of development: cardiomyocytes, epithelial cells, fibroblasts, and epicardium. They also have a clearly defined chamber that beats at 60 to 100 times per minute, the same rate of an embryos heart around the same age, the team reports today in Cell.

When I saw it the first time, I was amazed that these chambers could form on their own, says lead author Sasha Mendjan, a stem cell biologist at the Institute of Molecular Biotechnology at the Austrian Academy of Sciences. The amazing thing is that you see immediately whether the experiment worked and the organoid is functional, since it beatsunlike other organs.

The minihearts, which have so far survived for more than 3 months in the lab, will help scientists see heart development in unprecedented detail. They might also reveal the origins of cardiac problems like congenital heart defects in babies and cardiac cell death after heart attacks, Mendjan says. You cannot fully understand something until you can re-create it, he says, loosely quoting the Nobel physicist Richard Feynman.

Mendjan and his colleagues also froze pieces of the organoids to test their response to injury. They saw that cardiac fibroblasts, a type of cell responsible for maintaining tissue structure, migrated to the damaged areas to repair the dead cells, just as in babies that experience heart attacks. It has long been a mystery why babies hearts can regenerate after such injury without scarring, unlike those of adults. Now, we have a controlled and clean system outside of the human body to easily study this process, Mendjan says.

Aguirre says the next logical step is to connect beating heart organoids to vascular networks and test their ability to pump blood. Mendjans team plans to try to adjust the nutrient broth to produce organoids with all four chambers. With such advanced heart organoids, researchers could explore the many developmental heart problems that arise when these additional cavities start to form.

For Ma, growing a more adultlike heart organoid, with all its chambers and structures, is the future of the field. But he doesnt think this will happen in the next decade. For a complete heartlike organoid, he says, there is still a long way to go.

Continued here:
Lab-grown minihearts beat like the real thing - Science Magazine

DUBLIN, May 21, 2021 /PRNewswire/ -- The "Cell Therapy - Technologies, Markets and Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

This report describes and evaluates cell therapy technologies and methods, which have already started to play an important role in the practice of medicine. Hematopoietic stem cell transplantation is replacing the old fashioned bone marrow transplants. The role of cells in drug discovery is also described. Cell therapy is bound to become a part of medical practice.

The cell-based markets was analyzed for 2020, and projected to 2030. The markets are analyzed according to therapeutic categories, technologies and geographical areas. The largest expansion will be in diseases of the central nervous system, cancer and cardiovascular disorders. Skin and soft tissue repair, as well as diabetes mellitus, will be other major markets.

The number of companies involved in cell therapy has increased remarkably during the past few years. More than 500 companies have been identified to be involved in cell therapy and 316 of these are profiled in part II of the report along with tabulation of 306 alliances. Of these companies, 171 are involved in stem cells.

Profiles of 73 academic institutions in the US involved in cell therapy are also included in part II along with their commercial collaborations. The text is supplemented with 67 Tables and 26 Figures. The bibliography contains 1,200 selected references, which are cited in the text.

Stem cells are discussed in detail in one chapter. Some light is thrown on the current controversy of embryonic sources of stem cells and comparison with adult sources. Other sources of stem cells such as the placenta, cord blood and fat removed by liposuction are also discussed. Stem cells can also be genetically modified prior to transplantation.

Cell therapy technologies overlap with those of gene therapy, cancer vaccines, drug delivery, tissue engineering, and regenerative medicine. Pharmaceutical applications of stem cells including those in drug discovery are also described. Various types of cells used, methods of preparation and culture, encapsulation, and genetic engineering of cells are discussed. Sources of cells, both human and animal (xenotransplantation) are discussed. Methods of delivery of cell therapy range from injections to surgical implantation using special devices.

Cell therapy has applications in a large number of disorders. The most important are diseases of the nervous system and cancer which are the topics for separate chapters. Other applications include cardiac disorders (myocardial infarction and heart failure), diabetes mellitus, diseases of bones and joints, genetic disorders, and wounds of the skin and soft tissues.

Regulatory and ethical issues involving cell therapy are important and are discussed. The current political debate on the use of stem cells from embryonic sources (hESCs) is also presented. Safety is an essential consideration of any new therapy and regulations for cell therapy are those for biological preparations.

Key Topics Covered:

Part One: Technologies, Ethics & Regulations

Executive Summary

1. Introduction to Cell Therapy

2. Cell Therapy Technologies

3. Stem Cells

4. Clinical Applications of Cell Therapy

5. Cell Therapy for Cardiovascular Disorders

6. Cell Therapy for Cancer

7. Cell Therapy for Neurological Disorders

8. Ethical, Legal and Political Aspects of Cell therapy

9. Safety and Regulatory Aspects of Cell Therapy

Part II: Markets, Companies & Academic Institutions

10. Markets and Future Prospects for Cell Therapy

11. Companies Involved in Cell Therapy

12. Academic Institutions

13. References

For more information about this report visit https://www.researchandmarkets.com/r/oletip

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

SOURCE Research and Markets

http://www.researchandmarkets.com

Originally posted here:
Global Cell Therapy Markets, Technologies, and Competitive Landscape Report 2020-2030: Applications, Cardiovascular Disorders, Cancer, Neurological...

DUBLIN, May 21, 2021 /PRNewswire/ -- The "Cardiovascular Drug Delivery - Technologies, Markets & Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

The cardiovascular drug delivery markets are estimated for the years 2018 to 2028 on the basis of epidemiology and total markets for cardiovascular therapeutics.

The estimates take into consideration the anticipated advances and availability of various technologies, particularly drug delivery devices in the future. Markets for drug-eluting stents are calculated separately. The role of drug delivery in developing cardiovascular markets is defined and unmet needs in cardiovascular drug delivery technologies are identified.

Drug delivery to the cardiovascular system is approached at three levels: (1) routes of drug delivery; (2) formulations; and finally (3) applications to various diseases.

Formulations for drug delivery to the cardiovascular system range from controlled release preparations to delivery of proteins and peptides. Cell and gene therapies, including antisense and RNA interference, are described in full chapters as they are the most innovative methods of delivery of therapeutics. Various methods of improving the systemic administration of drugs for cardiovascular disorders are described including the use of nanotechnology.

Cell-selective targeted drug delivery has emerged as one of the most significant areas of biomedical engineering research, to optimize the therapeutic efficacy of a drug by strictly localizing its pharmacological activity to a pathophysiologically relevant tissue system. These concepts have been applied to targeted drug delivery to the cardiovascular system. Devices for drug delivery to the cardiovascular system are also described.

The role of drug delivery in various cardiovascular disorders such as myocardial ischemia, hypertension, and hypercholesterolemia is discussed. Cardioprotection is also discussed. Some of the preparations and technologies are also applicable to peripheral arterial diseases. Controlled release systems are based on chronopharmacology, which deals with the effects of circadian biological rhythms on drug actions. A full chapter is devoted to drug-eluting stents as treatment for restenosis following stenting of coronary arteries.Fifteen companies are involved in drug-eluting stents.

New cell-based therapeutic strategies are being developed in response to the shortcomings of available treatments for heart disease. Potential repair by cell grafting or mobilizing endogenous cells holds particular attraction in heart disease, where the meager capacity for cardiomyocyte proliferation likely contributes to the irreversibility of heart failure.

Cell therapy approaches include attempts to reinitiate cardiomyocyte proliferation in the adult, conversion of fibroblasts to contractile myocytes, conversion of bone marrow stem cells into cardiomyocytes, and transplantation of myocytes or other cells into injured myocardium.

Advances in the molecular pathophysiology of cardiovascular diseases have brought gene therapy within the realm of possibility as a novel approach to the treatment of these diseases. It is hoped that gene therapy will be less expensive and affordable because the techniques involved are simpler than those involved in cardiac bypass surgery, heart transplantation and stent implantation.

Gene therapy would be a more physiologic approach to deliver vasoprotective molecules to the site of vascular lesions. Gene therapy is not only a sophisticated method of drug delivery; it may at times need drug delivery devices such as catheters for transfer of genes to various parts of the cardiovascular system.

Selected 83 companies that either develop technologies for drug delivery to the cardiovascular system or products using these technologies are profiled and 80 collaborations between companies are tabulated. The bibliography includes 200 selected references from recent literature on this topic.

Key Markets

Key Topics Covered:

Executive Summary

1. Cardiovascular Diseases

2. Methods for Drug Delivery to the Cardiovascular System

3. Cell Therapy for Cardiovascular Disorders

4. Gene Therapy for Cardiovascular Disorders

5. Drug-Eluting Stents

6. Markets for Cardiovascular Drug Delivery

7. Companies involved in Cardiovascular Drug Delivery

8. References

For more information about this report visit https://www.researchandmarkets.com/r/qqxmpd

Media Contact:

Research and Markets Laura Wood, Senior Manager [emailprotected]

For E.S.T Office Hours Call +1-917-300-0470 For U.S./CAN Toll Free Call +1-800-526-8630 For GMT Office Hours Call +353-1-416-8900

U.S. Fax: 646-607-1907 Fax (outside U.S.): +353-1-481-1716

SOURCE Research and Markets

http://www.researchandmarkets.com

Originally posted here:
Global Cardiovascular Drug Delivery Markets Report 2021: Cell and Gene Therapies, Including Antisense and RNA Interference are Described in Detail -...

DUBLIN--(BUSINESS WIRE)--The "Cardiovascular Drug Delivery - Technologies, Markets & Companies" report from Jain PharmaBiotech has been added to ResearchAndMarkets.com's offering.

The cardiovascular drug delivery markets are estimated for the years 2018 to 2028 on the basis of epidemiology and total markets for cardiovascular therapeutics.

The estimates take into consideration the anticipated advances and availability of various technologies, particularly drug delivery devices in the future. Markets for drug-eluting stents are calculated separately. The role of drug delivery in developing cardiovascular markets is defined and unmet needs in cardiovascular drug delivery technologies are identified.

Drug delivery to the cardiovascular system is approached at three levels: (1) routes of drug delivery; (2) formulations; and finally (3) applications to various diseases.

Formulations for drug delivery to the cardiovascular system range from controlled release preparations to delivery of proteins and peptides. Cell and gene therapies, including antisense and RNA interference, are described in full chapters as they are the most innovative methods of delivery of therapeutics. Various methods of improving the systemic administration of drugs for cardiovascular disorders are described including the use of nanotechnology.

Cell-selective targeted drug delivery has emerged as one of the most significant areas of biomedical engineering research, to optimize the therapeutic efficacy of a drug by strictly localizing its pharmacological activity to a pathophysiologically relevant tissue system. These concepts have been applied to targeted drug delivery to the cardiovascular system. Devices for drug delivery to the cardiovascular system are also described.

The role of drug delivery in various cardiovascular disorders such as myocardial ischemia, hypertension, and hypercholesterolemia is discussed. Cardioprotection is also discussed. Some of the preparations and technologies are also applicable to peripheral arterial diseases. Controlled release systems are based on chronopharmacology, which deals with the effects of circadian biological rhythms on drug actions. A full chapter is devoted to drug-eluting stents as treatment for restenosis following stenting of coronary arteries.Fifteen companies are involved in drug-eluting stents.

New cell-based therapeutic strategies are being developed in response to the shortcomings of available treatments for heart disease. Potential repair by cell grafting or mobilizing endogenous cells holds particular attraction in heart disease, where the meager capacity for cardiomyocyte proliferation likely contributes to the irreversibility of heart failure.

Cell therapy approaches include attempts to reinitiate cardiomyocyte proliferation in the adult, conversion of fibroblasts to contractile myocytes, conversion of bone marrow stem cells into cardiomyocytes, and transplantation of myocytes or other cells into injured myocardium.

Advances in the molecular pathophysiology of cardiovascular diseases have brought gene therapy within the realm of possibility as a novel approach to the treatment of these diseases. It is hoped that gene therapy will be less expensive and affordable because the techniques involved are simpler than those involved in cardiac bypass surgery, heart transplantation and stent implantation.

Gene therapy would be a more physiologic approach to deliver vasoprotective molecules to the site of vascular lesions. Gene therapy is not only a sophisticated method of drug delivery; it may at times need drug delivery devices such as catheters for transfer of genes to various parts of the cardiovascular system.

Selected 83 companies that either develop technologies for drug delivery to the cardiovascular system or products using these technologies are profiled and 80 collaborations between companies are tabulated. The bibliography includes 200 selected references from recent literature on this topic.

Key Markets

Key Topics Covered:

Executive Summary

1. Cardiovascular Diseases

2. Methods for Drug Delivery to the Cardiovascular System

3. Cell Therapy for Cardiovascular Disorders

4. Gene Therapy for Cardiovascular Disorders

5. Drug-Eluting Stents

6. Markets for Cardiovascular Drug Delivery

7. Companies involved in Cardiovascular Drug Delivery

8. References

For more information about this report visit https://www.researchandmarkets.com/r/p5l8t6

Follow this link:
Global Cardiovascular Drug Delivery Markets Report 2021: Diseases, Methods, Cell Therapy, Gene Therapy, Drug-eluting Stents, Key Markets -...