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Genetically engineered B cells could produce super-antibodies to HIV

Researchers at Washington University School of Medicine in St. Louis have received a $6.2 million grant from the National Institutes of Health (NIH) to develop a gene therapy that would modify the immune systems B cells to spur them to produce broadly neutralizing antibodies against HIV. In theory, such an approach could control or eliminate the infection without need for ongoing antiretroviral therapy. Shown is the engineered adenovirus designed to deliver HIV superantibody genes into B cells.

HIV infections can be controlled with medication, but such therapy must continue throughout patients lives because no strategy exists to eliminate the virus from the body or control the infection without ongoing treatment.

With the aim of developing such a strategy, researchers at Washington University School of Medicine in St. Louis have received a $6.2 million grant from the National Institutes of Health (NIH) to develop a gene therapy that would modify the immune systems B cells to spur them to produce broadly neutralizing antibodies against HIV. In theory, such an approach could control or eliminate the infection without need for ongoing antiretroviral therapy.

Permanent ways to control or eliminate HIV infection remain elusive, and their development is a major goal of the field, said David T. Curiel, MD, PhD, the Distinguished Professor of Radiation Oncology. The idea of modifying B cells which naturally produce antibodies to ensure that they manufacture specific antibodies that are broadly effective at targeting HIV is an exciting strategy. We have brought together a great team with expertise in HIV, gene therapy, and animal models of infection to work toward this goal.

Curiels co-principal investigators are Michael R. Farzan, PhD, of Harvard Medical School and Boston Childrens Hospital, and Mauricio de Aguiar Martins, PhD, of the University of Florida.

Over the decades since HIV appeared, researchers have learned that about 1% of people with the virus are able to produce what might be considered superantibodies against the virus. Such individuals known as elite neutralizers can produce antibodies against multiple strains of HIV.

Some people naturally have antibodies that can bind and destroy or deactivate very diverse strains of HIV, and we now have the ability to build those types of antibodies in the lab, said Paul Boucher, a doctoral student in Curiels lab. But just giving other patients these superantibodies is not an ideal solution, because these proteins would stay in the body only temporarily. Instead, our approach is to genetically modify the cells responsible for making antibodies the immune systems B cells so they can always produce superantibodies against HIV whenever they may need to.

Such engineered B cells could create, in theory, a state of permanent vaccination against the virus. Even if such a gene therapy doesnt fully clear HIV from the body, the strategy could allow the amount of virus in the body to be controlled, keeping it at a minimal level and creating a functional cure, according to the researchers.

The strategy involves modifying a different type of virus, called adenovirus. When used in gene therapy, such viruses are genetically disabled so they cant cause disease. The researchers then could engineer the adenovirus to carry the gene responsible for manufacturing broadly neutralizing antibodies to HIV. In the same viral vector, they also could include genes responsible for manufacturing the CRISPR/Cas9 gene editing proteins. In this way, the gene therapy delivery vehicle would carry into the body both the antibody gene that will be edited into the B cell genome and the genes to build the molecular tools to carry out that editing.

Using a three-part targeting strategy, the researchers would design the adenovirus to deliver its genetic payload only to B cells, avoiding other cell types. They have developed ways to modify the virus so that it is targeted directly to a protein that is expressed on the surface of B cells and no other cell types. The researchers can further restrict the targeting by using genetic methods to ensure that the CRISPR/Cas9 proteins can only be manufactured when their genes are delivered into B cells. Finally, they have developed strategies to modify the adenovirus in a way that stops its natural tendency to accumulate in the liver.

This strategy to modify B cells is distinct from another adenoviral gene therapy approach to HIV treatment that is currently in clinical trials led by principal investigator Rachel M. Presti, MD, PhD, a professor of medicine in the Division of Infectious Diseases at Washington University School of Medicine. HIV is difficult to eliminate from the body because the virus integrates its genome into the DNA of the infected individuals T cells. The strategy currently in clinical trials is focused on using precise targeting of the CRISPR/Cas9 gene editing proteins to excise the virus from the genomes of all of a patients infected T cells. This strategy is being tested in a first-in-human, phase 1 clinical trial to determine its safety and preliminary efficacy at various doses.

Curiel said engineered B cells are ripe for developing new therapies to treat a wide variety of diseases. In November, a genetically engineered B cell therapy was administered to a patient for the first time at the University of Minnesota Medical Center. In that case, the therapy was designed to treat mucopolysaccharidosis type 1, a life-threatening condition in which the body lacks an enzyme necessary to break down large sugar molecules inside cells.

Gene therapy with engineered B cells is an exciting new area of research, Curiel said. We look forward to combining our expertise in adenovirus gene therapy, HIV infection and preclinical models of disease to realize our plan for developing an HIV therapy that we hope can permanently control the infection.

This work is supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), grant number 1R01-AI174270-01A1. This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

About Washington University School of Medicine

WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,900 faculty. Its National Institutes of Health (NIH) research funding portfolio is the second largest among U.S. medical schools and has grown 56% in the last seven years. Together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,900 faculty physicians practicing at 130 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Childrens hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

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$6.2 million to help develop gene therapy for HIV Washington University School of Medicine in St. Louis - Washington University School of Medicine in...

A type of gene therapy called CAR-T that has extended survival for thousands of patients with leukemia and other blood cancers is being adapted at UC San Francisco to treat people with glioblastoma, the most common and deadly adult brain tumor.

This new more powerful version of CAR-T employs a novel technology developed at UCSF called synthetic notch (synNotch) that both protects healthy tissue from damage and enables the treatment to work more effectively.

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Approximately 12,000 Americans are diagnosed each year, with an average survival of just 15 months.

UCSF opened enrollment this week for a clinical trial that is using the technology for the first time in people. A second trial, also at UCSF, is slated for 2025.

Approximately 12,000 Americans are diagnosed each year with glioblastoma. Patients survive on average for just 15 months after their diagnosis, and new treatments are urgently needed.

This project is a prime example of bench-to-bed translation within UCSF, representing the strengths in basic and clinical science, said Hideho Okada, MD, PhD, a physician-scientist and director of the UCSF Brain Tumor Immunotherapy Center. We have a truly home-grown project here.

Okada has received up to $11 million for the first trial from the California Institute for Regenerative Medicine (CIRM), which funds stem cell and gene therapy research for incurable diseases and disorders through all stages of clinical trial development.

Initial funding for the second trial is provided by the National Cancer Institute Specialized Programs of Research Excellence (NCI SPORE).

We hope that the treatment will prolong lives for patients with glioblastoma, said Okada, who is a professor of neurosurgery at UCSF and a member of the Weill Institute for Neurosciences. However, the primary goal of the current phase 1 study is to ensure safety and characterize any toxicities.

When tested in mice, Okada said the therapy provided a robust and long-lasting result that was more remarkable than anything he had encountered during 30 years of brain tumor research.

The CIRM-funded trial will be led by principal investigator Jennifer Clarke, MD, MPH. It is open to patients with newly diagnosed glioblastoma, who have completed standard-of-care treatment. Tumors must have a mutation found in approximately 20% of glioblastomas, and that can be identified by the UCSF500 cancer gene panel test.

The second study will be open to glioblastoma patients whether or not they have the mutation.

CAR-T refers to chimeric antigen receptor T-cells, which are cancer-killing immune cells that have been extracted from the patient and genetically modified to recognize and destroy antigens that appear on the surface of cancer cells. These supercharged CAR-T cells are then infused back into the body to attack tumor cells.

For many patients with leukemia and other blood cancers, CAR-T has demonstrated long-term remission, but the approach hasnt worked against brain tumors. Glioblastoma cells are more diverse than blood cancer cells, and they can evade CAR-T. Many of the antigens made by the tumors are also found in healthy tissue, leaving them open to attack.

To overcome these obstacles, Okada drew from the synNotch system developed by Wendell Lim, PhD, director of the UCSF Cell Design Institute and professor in the UCSF Department of Cellular and Molecular Pharmacology.

The technology allowed scientists to program CAR-T cells to target specific antigens on tumor cells, without touching those found in healthy tissue. They also do not succumb to T-cell exhaustion, a common problem with CAR-T therapies, because they are more metabolically stable and use less energy to fight cancer longer.

Weve created a system that is flexible and thorough and addresses the major concerns weve had about using CAR-T cells against solid tumors, Lim said. These cells act like computers: integrating multiple units of information and making complex decisions.

About the California Institute for Regenerative Medicine (CIRM): AtCIRM, we never forget that we were created by the people of California to accelerate stem cell treatments to patients with unmet medical needs, and act with a sense of urgency to succeed in that mission. To meet this challenge, our team of highly trained and experienced professionals actively partners with both academia and industry in a hands-on, entrepreneurial environment to fast track the development of todays most promising stem cell technologies. With $5.5 billion in funding and more than 150 active stem cell programs in our portfolio,CIRMis one of the worlds largest institutions dedicated to helping people by bringing the future of cellular medicine closer to reality.

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Gene Therapy Is Halting Cancer. Can It Work Against Brain Tumors? - UC San Francisco

Gene therapy research is booming. Since the U.S. Food and Drug Administration (FDA) issued its first approval for a gene therapyin 2017, oncology researchers have been breaking barriers in gene therapy trials, followed by an explosion in mRNA research during the COVID pandemic. Today, this trailblazing science is providing new ways to approach rare diseases and new hope when other investigational interventions have failed. In fact, themajorityof approved gene therapies are for rare diseases 14 are currently in Phase III trials for 10 rare diseases and 45 gene therapies are in early stages of development to treat 30 rare diseases. We see great potential for gene therapies, said Leslie Johnston, senior vice president of biotech delivery for Parexel. As more products are approved, it will gain traction and more companies will look to expand their therapies into other therapeutic indications. This progress presents tremendous potential to change more patients lives across many different diseases. This could be gene therapys moment. But to fully seize it, the industry must clear some complex hurdles. Gene therapies pose several unique challenges for clinical research, including ethical and safety considerations, regulatory hurdles, precarious logistics, and potentially staggering costs. These challenges may already be having ramifications: New U.S. patients treated with gene therapies approved or in development areexpected to fallby one-third from 2025 to 2034. The key to clearing these hurdles? Cooperation between sponsors, sites, regulators, patients, and other stakeholders is essential to expediting the advancement of life-saving gene therapies. Regulators should address risks without limiting innovation Gene therapy trials are strictly regulated and rightly so, due to the novel nature of the intervention and the potential long-term consequences. Gene therapy interventions also carry inherent safety risks, including the potential for unintended genetic changes or adverse immune reactions. Ensuring patient safety requires rigorous monitoring and adherence to strict protocols. However, obtaining regulatory approval under these conditions is time consuming and resource intensive. To avoid hampering scientific progress, regulators should aim to ensure that requirements are appropriately rigorous without being unmanageably onerous. Thankfully, the FDA is paying close attention to gene therapy and has demonstrated a desire to work with drug developers toward the success and approval of these treatments. Dr. Peter Marks, Director of the Center for Biologics Evaluation and Research (CBER) at the FDA, has expressed his hope for an exponential, if not logarithmic, increase in gene therapy approvals. There is a lot of excitement that this could potentially make a big difference for the treatment of human disease, said Dr. Marks in hisremarksto the National Press Forum last November. The FDA is going beyond mere rhapsodizing and taking action to accelerate gene therapy. Last year, the agencylaunched a pilot programcalled Support for Clinical Trials Advancing Rare Disease Therapeutics, or START. This program is designed to accelerate the development and approval process for treatments targeting rare diseases by providing regulatory guidance, assistance, and incentives to sponsors conducting clinical trials in this field. The program represents an important step forward in fostering innovation and collaboration between regulatory bodies and sponsors. In addition, the FDA is working toharmonize global requirementsfor the review of gene therapies. Encouraging and facilitating international cooperation and harmonization of regulatory standards including mutual recognition agreements and shared regulatory pathways for multinational clinical trials can help streamline gene therapy development globally and help bring innovations to patients faster. Even with this progress, regulators should continue to help accelerate gene therapy research by streamlining regulatory pathways specifically tailored to gene therapies. This means providing clear guidance on requirements for preclinical and clinical development, fostering collaboration between stakeholders to share knowledge and best practices, and offering expedited review processes for gene therapy products aimed at treating serious or life-threatening diseases. With a staggering2,500 cell and gene therapyinvestigational new drug applications (INDs) on file, the FDA approved justfivecell and gene therapies in 2023. Dr. Marks hassuggestedthat accelerated approval, which has successfully advanced cancer and HIV/AIDS treatments, may be the most appropriate path for this new category of treatments. But, regulators also need to commit to proactively partner with developers to understand the patient population and the risks and benefits of each new therapy. Likewise, researchers, industry stakeholders, and patient advocacy groups should engage with regulators to help them understand the unique challenges and opportunities in the field of gene therapy. This can help regulators adapt regulatory frameworks to ensure patient safety while expediting the development and approval of promising treatments. Sites and sponsors must be prepared Of course, sites and sponsors also have a crucial part to play in advancing this promising field of medicine. Clinical trial sites should enhance their capacity to conduct gene therapy trials safely and effectively and sponsors should do their part to assist sites in these efforts. By working closely with clinicians and regulators, sponsors can ensure that the trial development process aligns with clinical needs and regulatory standards. Sponsors should have a thorough understanding of FDA requirements pertaining to design, preclinical testing, and long-term follow-up. Better alignment from the outset will lead to more efficient trial designs, faster regulatory approvals, and ultimately quicker patient access to therapies. For example, sponsors working with mRNA and other genetically engineered therapies in North America not only have to go through institutional review board (IRB) review, they also have to navigate additional requirements from the U.S. National Institutes of Health (NIH) Office of Science PolicyGuidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules(NIH Guidelines). These requirements usually involve an additional biosafety risk assessment review from an institutional biosafety committee (IBC) in addition to IRB review. NIH Guidelines apply for any research involving recombinant or synthetic nucleic acids (e.g. genetically engineered materials) that receives NIH support or takes place at sites that have received NIH support for such research. Even when there is zero NIH support, IBC review is considered a best practice. IBC review and inspection helps sites ensure they are fully prepared by identifying areas for improved biosafety protections and calling out gaps in current standard operating procedures (SOPs). Proactive coordination and integration of these separate review processes can speed trial timelines and help sponsors consistently address any potential concerns or issues. Sites can also be better prepared by pre-registering an IBC. The NIH takes six to eight weeks or more to approve a new registration, in addition to IBC review time so by registering an IBC before they even have a trial, sites can save a month or more in startup time over a site that waited to register. Clinical trial sites looking to host gene therapy studies must be prepared in other ways, as well, both in terms of knowledge and infrastructure. Gene therapy studies require specialized infrastructure for manufacturing, storing, and administering genetic material to adhere to strict biosafety guidelines. Something as simple as having an upholstered chair in the infusion room which would pose an unacceptable contamination risk if genetic materials were to spill would require the site to rethink their current processes. Rigorous training is also key due to the added risk of spreading genetic material to caregivers and others in close contact with patients. Research staff must be specially trained to handle, deliver, and dispose of this material safely. Of course, these measures can seem intimidating for sites that are already cost-constrained. Large academic medical centers with more resources and experience are more likely to be well-positioned for these studies. For instance, they may already have conducted bench, animal, and/or agricultural research with genetic engineering or have the funding to make any needed adjustments such as purchasing special equipment. But to maximize the potential number of sites where this research can be conducted and therefore reach more potential participants sponsors might consider providing help in the form of financial assistance, training curricula, SOP guidance, and more to smaller sites seeking to conduct gene therapy research. Logistical complexities depending on the investigational medicine and therapeutic area are among the most complicated challenges in gene therapy trials, added Johnston. From collecting the specimen from the patient, modifying it, storing it, transporting it, and then returning it back to the patient all comes with tremendously unique logistical challenges and requires equally unique equipment, technology, and expertise. And it can be cost-prohibitive. Patients must be fully on board Of course, the most essential stakeholder in any clinical trial is the patient. In gene therapy research, which can be particularly demanding, patients must have a complete understanding of and commitment to their involvement. Understanding the potential risks and benefits can help patients make informed decisions and navigate the study process. First, it's crucial for patients to adhere strictly to the protocol provided by the clinical trial team, including following medication schedules, maintaining specific hygiene practices, and attending all study visits. They should strive to maintain optimal health to enhance the body's response to gene therapy. And to avoid delays, patients should maintain open and honest communication with the clinical trial team, reporting any changes in symptoms, side effects, or general health as soon as they occur. Trial participants also need to be in it for the long haul. Because gene therapy interventions aim to produce lasting effects, even cures, they typically require long-term patient follow-up to assess efficacy and safety. But they may also need to have incredible patience. Johnston explained, There are many complexities that can impact study progress. For example, unpredictable logistical challenges like a weather event or vehicle accident could delay a temperature-sensitive delivery to a site, or data review outcomes could require an indeterminate pause period. Patience and agility are must-haves, but it is difficult for patients potentially depending on this new therapy to save or change their lives. Lastly, the industry cannot forget the patient. Involving patients and patient advocacy groups in the regulatory process can help ensure that the development of gene therapies is aligned with patient needs and priorities, as well as shed light on risk-benefit perspectives from a patients viewpoint. The more these perspectives are considered from the beginning, the greater the chance of a trials success. Rita Naman, co-founder of the Mighty Milo Foundation, emphasizes the need for a more collaborative and patient-centered approach to gene therapy development. "For ultra-rare diseases likeSPAX5, gene therapy offers a glimmer of hope where traditional treatments do not. But logistical hurdles make these therapies expensive and inaccessible, explained Naman. Closer collaboration with patients, industry, and regulators could streamline these processes, drive costs down, and speed trials. Patients like my son, and their caregivers, plus advocacy groups should be invited into the earliest discussions to prevent false starts or missed milestones in gene therapy development especially as the patients priorities dont always line up with the sponsors. In the fight for gene therapy breakthroughs, cooperation is key. The road to operationalizing gene therapy clinical trials is laced with land mines and potholes. To capture the full potential of novel gene therapy research, a new level of collaboration between sponsors, CROs, sites, oversight committees, regulatory bodies, and patients is paramount. Patients want access to novel gene treatments, and they want it fast. Sponsors want to deliver but fight logistical and financial obstacles. Regulators want to ensure safety first, especially considering such new, promising science, concluded Johnston. These three goals may seem conflicting at times, so we need to strike a balance of safety and speed, so patients dont miss their only potential treatment opportunity. A seasoned industry veteran with more than 25 years of experience, James Riddle is senior vice president of global review operations at Advarra. Riddles expertise includes large program management and growth, operational processes, development and implementation of technology solutions, and management of large Human Research Protection Programs (HRPP), Biosafety programs (IBC) and Institutional Animal Care and Use programs (IACUC). Riddle has directed numerous clients in achieving Part 11 compliance and meeting computer system validation requirements.

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Gene Therapy is Having its Moment: Can the Clinical Research Ecosystem Seize It? - Contract Pharma

One of their biggest successes uses gene therapy to treat a rare genetic disorder called aromatic L-amino acid decarboxylase (AADC) deficiency.

Children with AADC deficient are missing the enzyme that produces dopamine and serotonin in the central nervous system. This affects pathways in the brain responsible for motor function and emotions.

As a result, these children cant coordinate the movements of their head, face and neck. They often dont reach normal childhood milestones, such as sitting up or walking by themselves.

Along with her mother, Arcelia Ramirez, they traveled 800 miles from their home near Omaha, Neb., so that Delilah could have this life-changing gene therapy surgery at Ohio State Wexner Medical Center.

But now, Delilah has changed so much for the better. On her 9th birthday, she blew out a candle on her cupcake on purpose. This was the first time she had ever blown out a birthday candle.

She's like a different kid. Her sleeping is a lot better. She can walk now, she can self-feed, said Arcelia Ramirez. When she started using a fork, that was a reason to celebrate. When she started using a straw, that was a reason to celebrate. Walking was a big, big milestone for her that we just celebrated.

So we are bringing in a correctly spelled sequence of the gene, said Bankiewicz, who is also chief scientific officer at the Ohio State Gene Therapy Institute.

This helps ensure we put the genetic material in exactly the right place, so the brain will start making dopamine and serotonin again, said Elder, who also is a professor of neurological surgery. This

therapy is designed to approach both parts of the brain that control movements and emotions.

This breakthrough in treating patients with AADC was decades in the making.

It requires a use of the technology and devices that we had to develop and establish over the years to do these surgeries very precisely, very carefully and then do it safely, Bankiewicz said. The issue of, Is it going to work? It's no longer being questioned. It works.

In addition to expanding this method to central nervous system diseases such as Alzheimers, Parkinsons, Multiple System Atrophy and Huntingtons disease, Elder and Bankiewicz are also trying to edit genetic mutations in other neurological disorders, including brain tumors.

We are not treating a gene that causes Parkinson's or Alzheimer's, Bankiewicz said. We're using this technology to deliver a therapeutic that we believe will, in a positive way, affect the progression of the disease.

# # #

Media Contact: Eileen Scahill, Wexner Medical Center Media Relations, Eileen.Scahill@osumc.edu

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The future of gene therapy has arrived, and it's changing lives - Wexner Medical Center - The Ohio State University

The global gene therapy market size was valued at USD 8.75 billion in 2023 and is poised to grow from USD 10.47 billion in 2024 to USD 52.40 billion by 2033, growing at a CAGR of 19.6% in the forecast period (2024-2033).

Gene therapy is a technique that uses a gene to treat, prevent or cure a disease or medical disorder. Often, gene therapy works by adding new copies of a gene that is broken, or by replacing a defective or missing gene in a patients cells with a healthy version of that gene. Both inherited genetic diseases (e.g., hemophilia and sickle cell disease) and acquired disorders (e.g., leukemia) have been treated with gene therapy.

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The development of the market is owing to an increase in the number of gene therapy-based discoveries, increasing investment in this sector, and rising approval of gene therapy products. According to the WHO, 10 to 20 new cell and gene therapies are expected to be approved each year by 2025.

Continuous developments in recombinant DNA technology are anticipated to enhance the efficiency of gene therapy in the coming years. Hence, ongoing progresses in recombinant DNA technology are anticipated to expand the number of ongoing clinical trials for gene therapy. Primarily, these advancements are taking place in the context of various gene-editing tools and expression systems to augment the R&D for products. The advent of CRISPR/Cas9 nuclease, ZFN, and TALEN allows easy & precise genome editing. As a result, in recent times, the gene-editing space has witnessed a substantial number of research activities, which, in turn, is expected to influence the growth of the gene therapy market.

The growth of the gene therapy market is expected to be majorly benefitted from the increasing prevalence of cancer. The ongoing increase in cancer patients and related death per year emphasizes the essential for the development of robust treatment solutions. In 2020, there were around 18.1 million new cases of cancer worldwide. 9.3 million of these cases involved men, while 8.8 million involved women. Continuing developments in tumor genetic studies have delivered substantial information about cancer-related molecular signatures, which in turn, is expected to support ongoing clinical trials for cancer therapeutics.

With rising demand for robust disease treatment therapies, companies have focused their efforts to accelerate R&D for effective genetic therapies that target the cause of disease at a genomic level. . Furthermore, the U.S. FDA provides constant support for innovations in this sector via a number of policies with regard to product manufacturing. In January 2020, the agency released six final guidelines on the manufacturing and clinical development of safe and efficient products.

Furthermore, facility expansion for cell and gene therapies is one of the major factors driving the gene therapy market growth. Several in-house facilities and CDMOs for gene therapy manufacturing have begun investing to enhance their production capacity, which, in turn, is anticipated to create lucrative opportunities for market players. For instance, in April 2022, the FDA approved commercial licensure approval to Novartis for its Durham, N.C. site. This approval permits the 170,000 square-foot facility to make, test, and issue commercial Zolgensma, as well as manufacture therapy products for current & upcoming clinical trials.

Cell and Gene Therapy Market :https://www.biospace.com/article/releases/u-s-cell-and-gene-therapy-clinical-trial-services-industry-is-rising-rapidly/

Gene Therapy Market Report Highlights

U.S. Gene Therapy Market Size in U.S. 2024 to 2033

The U.S. gene therapy market size was estimated at USD 3.19 billion in 2023 and is projected to surpass around USD 18.50 billion by 2033 at a CAGR of 19.22 % from 2024 to 2033.

North America dominated the market in 2023 with the largest revenue share of 65.12% in 2023. This region is expected to become the largest routine manufacturer of gene therapy in terms of the number of approvals and revenue generated during the forecast period. Increasing investments in R&D from large and small companies in the development of ideal therapy drugs are anticipated to further boost the market.

Furthermore, the increasing number of investments by the governments and the growing prevalence of targeted diseases are the factors fueling the market. According to the Spinal Muscular Atrophy Foundation, in 2020, around 10,000 to 25,000 children and adults in the U.S. were affected by spinal muscular atrophy, making it a fairly common disease among rare diseases.

Europe is estimated to be the fastest-growing regional segment from 2024 to 2030. This is attributed to its large population with unmet medical needs and increasing demand for novel technologies in the treatment of rare but increasingly prevalent diseases. Asia Pacific market for commercial application of genetic therapies is anticipated to witness significant growth in the forecast period, which can be attributed to the easy availability of resources, local presence of major companies, and increased investment, by the governments.

UK Gene Therapy Market

The UK gene therapy market is anticipated to witness accelerated growth over the forecast period, due to increased investments by various big companies and governments, including the NHS & research laboratories. For instance, in March 2022, the UK government invested USD 326.45 million to accelerate healthcare research and manufacturing. Under this investment, additional $80 million of the fund will help companies at the forefront of invention with their commercial-scale manufacturing investments in areas like gene and cell therapies, as well as improved diagnostic technologies, among others. Various mergers & partnerships between manufacturers, universities, and other government bodies are expected to boost the market over the forecast period.

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What is gene therapy used for?

Most gene therapies are still in the clinical trial phase. Clinical trials play an important role in finding treatments that are safe and effective. Clinical trials are investigating gene therapy for the treatment ofcancer,macular degenerationand other eye diseases, certaingenetic conditionsandHIV/AIDS.

The U.S. Food and Drug Administration (FDA) has approved two gene therapies for use in the U.S.:

Is gene therapy safe?

The first gene therapy trial was run more than thirty years ago. The earliest studies showed that gene therapy could have very serious health risks, such as toxicity, inflammation, and cancer. Since then, researchers have studied the mechanisms and developed improved techniques that are less likely to cause dangerous immune reactions or cancer. Because gene therapy techniques are relatively new, some risks may be unpredictable; however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy research, clinical trials, and approved treatments are as safe as possible.

Comprehensive federal laws, regulations, and guidelines help protect people who participate in research studies (called clinical trials). The U.S. Food and Drug Administration (FDA) regulates all gene therapy products in the United States and oversees research in this area. Researchers who wish to test an approach in a clinical trial must first obtain permission from the FDA. The FDA has the authority to reject or suspend clinical trials that are suspected of being unsafe for participants.

The National Institutes of Health (NIH) also plays an important role in ensuring the safety of gene therapy research. NIH provides guidelines for investigators and institutions (such as universities and hospitals) to follow when conducting clinical trials with gene therapy. These guidelines state that clinical trials at institutions receiving NIH funding for this type of research must be registered with the NIH Office of Biotechnology Activities. The protocol, or plan, for each clinical trial is then reviewed by the NIH Recombinant DNA Advisory Committee (RAC) to determine whether it raises medical, ethical, or safety issues that warrant further discussion at a RAC public meeting.

An Institutional Review Board (IRB) and an Institutional Biosafety Committee (IBC) must approve each gene therapy clinical trial before it can be carried out. An IRB is a committee of scientific and medical advisors and consumers that reviews all research within an institution. An IBC is a group that reviews and approves an institution's potentially hazardous research studies. Multiple levels of evaluation and oversight ensure that safety concerns are a top priority in the planning and carrying out of gene therapy research.

The clinical trial process occurs in three phases. Phase I studies determine if a treatment is safe for people and identify its side effects. Phase II studies determine if the treatment is effective, meaning whether it works. Phase III studies compare the new treatment to the current treatments available. Doctors want to know whether the new treatment works better or has fewer side effects than the standard treatment. The FDA reviews the results of the clinical trial. If it determines that the benefits of the new treatment outweigh the side effects, it approves the therapy, and doctors can use it to treat a disorder.

What are CAR T cell therapy, RNA therapy, and other genetic therapies?

Several treatments have been developed that involve genetic material but are typically not considered gene therapy. Some of these methods alter DNA for a slightly different use than gene therapy. Others do not alter genes themselves, but they change whether or how a genes instructions are carried out to make proteins.

Cell-based gene therapy

CAR T cell therapy (or chimeric antigen receptor T cell therapy) is an example of cell-based gene therapy. This type of treatment combines the technologies of gene therapy and cell therapy. Cell therapy introduces cells to the body that have a particular function to help treat a disease. In cell-based gene therapy, the cells have been genetically altered to give them the special function. CAR T cell therapy introduces a gene to a persons T cells, which are a type of immune cell. This gene provides instructions for making a protein, called the chimeric antigen receptor (CAR), that attaches to cancer cells. The modified immune cells can specifically attack cancer cells.

RNA therapy

Several techniques, called RNA therapies, use pieces of RNA, which is a type of genetic material similar to DNA, to help treat a disorder. In many of these techniques, the pieces of RNA interact with a molecule calledmessenger RNA(or mRNA for short). In cells, mRNA uses the information in genes to create a blueprint for making proteins. By interacting with mRNA, these therapies influence how much protein is produced from a gene, which can compensate for the effects of a genetic alteration. Examples of these RNA therapies include antisense oligonucleotide (ASO), small interfering RNA (siRNA), and microRNA (miRNA) therapies. An RNA therapy called RNA aptamer therapy introduces small pieces of RNA that attach directly to proteins to alter their function.

Epigenetic therapy

Another gene-related therapy, called epigenetic therapy, affectsepigenetic changesin cells. Epigenetic changes are specific modifications (often called tags) attached to DNA that control whether genes are turned on or off. Abnormal patterns of epigenetic modifications alter gene activity and, subsequently, protein production. Epigenetic therapies are used to correct epigenetic errors that underlie genetic disorders.

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Vector Insights

The AAV segment shows a significant revenue contribution of 22.9% in 2023. Several biopharma companies are offering their viral vector platform for the development of AAV-based gene therapy product. For instance, in September 2016, Lonza signed an exclusive agreement with Massachusetts Eye and Ear to support its novel Anc-AAV gene therapy platform for development and commercialization of next-generation gene therapies based on their AAV platform. Similarly, RegenxBio had made an agreement with companies AveXis & Biogen in March 2014 and May 2016, respectively, which would allow both companies to use RegenxBios AAV vector platform for development of gene therapy molecules. Furthermore, in May 2021, Biogen Inc. and Capsigen Inc. entered into a strategic research partnership to engineer novel AAV capsids that have the possibility to deliver transformative gene therapies, which can address the fundamental genetic causes of numerous neuromuscular and CNS disorders. In July 2021, the U.S. Department of Commerces National Institute of Standards and Technology (NIST), National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), and United States Pharmacopeia (USP) announced a collaboration to evaluate analytical methods and develop standards for AAV. As part of this partnership, NIST and USP will be conducting an interlaboratory study in which several laboratories will measure these serious quality attributes, and their results will be linked and examined. This collaboration will support the development of new promising gene therapies that will significantly advance peoples lives.

Indication Insights

The spinal muscular atrophy (SMA) segment dominated the market in 2023. Although SMA is a rare disorder, it is one of the most common fatal inherited diseases of infancy. The development of Zolgensma (AVXS-101), has proven its effectiveness in treating SMA and altering the phenotype of the illness. The FDA approved Novartis' Zolgensma approval in May 2019, which is aimed at treating the underlying cause of SMA. As of now, Zolgensma is the only gene treatment in this field to have been approved. The approval of this gene therapy is evidence of the growing use of therapies to treat serious hereditary illnesses like SMA.

The Beta-Thalassemia Major/SCD segment is anticipated to register the fastest CAGR over the forecast period. Gene therapy for SCD and -thalassemia is based on transplantation of gene-modified hematopoietic stem cells. Clinical and preclinical studies have shown the efficacy and safety of this therapeutic modality. However, several other factors, such as suboptimal gene expression levels & gene transfer efficiency, limited stem-cell dose and quality, and toxicity of myeloablative regimens are still hampering its efficacy. Despite these challenges, in June 2019, bluebird Bios Zynteglo (formerly LentiGlobin) received conditional approval in Europe for the treatment of -thalassemia and is expected to receive U.S. FDA approval in August 2022. Moreover, the product has already received Orphan Drug status by the U.S. FDA for treatment of patients with sickle cell disease (SCD). Furthermore, in April 2021, Vertex Pharmaceuticals and CRISPR Therapeutics amended partnership for the development, production, and commercialization of CTX001 in sickle beta thalassemia and cell disease. These achievements in this segment are anticipated to significantly boost the adoption of the product in this segment.

Route of Administration Insights

The intravenous segment dominated the global gene therapy market in 2023. Large number of approved products along with strong pipeline for IV candidates is the major reason for the segment dominance. The segment is also expected to emerge as the most lucrative over the forecast period.

Recent Developments

Some of the prominent players in the Gene therapy market include:

Segments Covered in the Report

This report forecasts revenue growth at global, regional, and country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2021 to 2033. For this study, Nova one advisor, Inc. has segmented the global gene therapy market.

Indication

Vector Type

Route of Administration

By Region

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Gene Therapy Market Size Poised to Surge USD 52.40 Billion by 2033 - BioSpace

The global cancer gene therapy market size was accounted for USD 2.95 billion in 2023 and it is increasing around USD 18.11 billion by 2033 with a CAGR of 19.9% from 2024 to 2033, according to a new report by Nova One Advisor.

Cancer Gene Therapy Market Overview

Cancer is a group of diseases that involve abnormal cell growth which can spread to respective parts of the body. Cancer can spread throughout the human body.Gene therapyis a kind of treatment in which the genes that are not normal or are missing in the patients cells are replaced with normal genes. Cancer gene therapy is a technique for treating cancers where the therapeutic DNA is introduced in the gene of the individual suffering from cancer.

Due to a high success rate in preclinical as well asclinical trials, cancer gene therapy is gaining high popularity all over the world. There are numerous techniques utilized in cancer gene therapy. In one of the gene therapy techniques, either the mutated gene is replaced with a healthy gene, or the gene is inactivated if its function is abnormal. In a newly developed technique, new genes can be introduced in the body of the patient to help fight against cancer cells.

Further, the ongoing extensive research and development (R&D) strategies implemented bybiopharmaceuticalfirms for producing novel therapeutic drugs are driving the market growth notably.

The market players can aim towards expansions, collaborations, joint ventures, acquisitions, and partnerships to advance capabilities in gene therapy. This would help in yielding effective therapeutic drugs for treating different kinds of cancers. In April 2022, GSK plc announced the acquisition of Sierra Oncology for 1.6 billion ($1.9 billion). This acquisition would help GSK plc in enhancing its capabilities with respect to targeted therapies for treating rare forms of cancer.

Biotechnologyfirms are evaluating novel gene therapy vectors for increasing levels of protein production/gene expression, reducing immunogenicity, and improving durability.

The top cancers in terms of the count of new cases in 2020 all over the world were Lung Cancer (2,206,771 cases),Breast Cancer(2,261,419 cases),Prostate Cancer(1,414,259 cases), Colorectal Cancer (1,931,590 cases), Stomach Cancer (1,089,103 cases), and Liver cancer (905,677 cases). In 2018, there were around 134,632 new cancer cases and 89,042 cancer-related fatalities. Breast and liver cancers were among the most common tumors in terms of incidence and mortality. The high prevalence of breast cancer cases enhances the scope for CRISPR/Cas9-based gene editing for breast cancer therapy and VISA-claudin4-BikDD gene therapy.

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Key Takeaways:

Cancer Gene Therapy Market Size in U.S. 2024 to 2033

The U.S. cancer gene therapy market size was valued at USD 1.25 billion in 2023 and is anticipated to reach around USD 7.94 billion by 2033, growing at a CAGR of 20.31% from 2024 to 2033.

North America accounted for the largest share of over 61.15% in 2023. This is attributed to the conducive environment facilitated by the government and the National Cancer Institute that supports research and development activities to enhance cancer therapeutics. Further, the presence of key market players in the region, their research efforts in devising gene therapy for cancer treatment, and collaborative efforts among market players to enhance research are boosting the market growth in the region. For instance, in August 2022, Merck & Co., Inc., collaborated with Orna Therapeutics Inc., for discovery, development, and commercialization of multiple programs, inclusive of utilization of mRNA for cancer gene therapy.

Europe is estimated to be the fastest-growing region over the forecast period due to increase in research funding for novel therapeutics by government bodies and increasing demand for novel therapeutics that could help combat the growing incidence of cancer cases across the region. Moreover, The European Unions Horizon Europe Mission on Cancer was launched in September 2023 so as to offer funds to a broad spectrum of activities that are intended to lower Europes cancer burden by accelerating research and innovation in cancer therapeutics. The mission is anticipated to help over 3 million cancer survivors by the year 2033.

The cancer gene therapy market in the Asia Pacific (APAC) region is segmented into India, China, Japan, South Korea, and the rest of the Asia Pacific (APAC) region. China dominated the Asia Pacific region followed by Japan and India in 2023.

The Latin America, Middle East, and African (LAMEA) cancer gene therapy market is segmented into North Africa, South Africa, Saudi Arabia, Brazil, Argentina, and the Rest of LAMEA. The Middle East and the Latin America region are anticipated to have notable growth in the cancer gene therapy market during the forecast period. Brazil held the largest share in the LAMEA region in 2023. Due to low literacy, uncertainty, and civil war in African countries, the cancer gene therapy market in Africa is expected to grow at a comparatively slow rate.

What are the importance of Cancer Gene Therapy?

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Types of gene therapy for cancer

Gene therapy aims tocontrolthe altered genesor genetic mutationsof a cancertoprevent the cancers growth.This approach to using our own cells and genes to treat cancer is called somatic gene therapy.Thistype of gene therapydoes not impact germ-line cells in the reproductive system, meaning none of the genetic changescan bepassedon to otherfamily members.

There are four types of somatic gene therapy: gene editing; gene replacement; gene addition; and gene inhibition.

Gene editing is correcting the cells gene to fix the imbalance by snipping out the faulty part of the gene and changing the cancers DNA. This type of gene therapy may correct the alteration rather than trying to remove it. Gene replacement is just that: replacing the faulty or nonworking gene with a healthy copy of it. This type of gene therapy is another form of trying to fix the genetic change rather than trying to remove it.

Gene addition is adding novel genetic code to a different cell usually an immune system fighter cell to help it combat the protein linked to the damaged gene. CAR T-cell therapy is an example of gene addition. This form of gene therapy isnt adding a copy of an already-existing gene but rather an entirely new gene usually with the intent of killing the cancer cell via the immune system. Doctors may also add a new gene directly to the cancer cell that causes the cancer cell to commit apoptosis (kill itself).

Gene inhibition simply shuts down the faulty gene. This can either kill the cell or prevent it from acting in a cancerous manner, such as growing and replicating exponentially.

Steps of gene therapy

Gene therapy is a new and potentially curative approach to treating cancer, but researchers still have so much to learn. While the steps below may seem straightforward, each part of the process requires years of study to develop the technologies.

Researchers must first identify the gene and protein linked to the cancer. The next steps are:

Steps of CAR T-cell therapy

CAR T-cell therapy has a slightly different process than more direct forms of gene therapy. CAR T cells are lab-generated fighter cells with specific, anti-cancer genetic code. Adding this genetic code is the gene therapy component of CAR T-cell therapy. CAR stands for chimeric antigen receptor, which is the new genetic code added to the T cells.

There are six CAR T-cell therapy agents approved by the U.S. Food and Drug Administration for different blood cancers. These approvals validate CAR T cells as an effective form of cancer gene therapy to improve patient life expectancy.

Doctors first draw blood from a patient and separate the T cells, which are white blood cells leading the immune systems defense against viruses, diseases and more unwanted intruders. T cells aim to protect the body from cancer, but theyre often ineffective at doing so.

The process of drawing blood from patients and separating the T cells is called apheresis.

After removing T cells from the body, the steps of CAR T-cell therapy are:

A similar process occurs for CAR NK-cell therapy. Scientists create chimeric antigen receptors to strengthen natural killer (NK) cells, another white blood cell of the immune system.

How long does CAR T-cell therapy take?

There are six CAR T-cell therapies approved for types of three blood cancers: myeloma, leukemia and lymphoma. CAR T-cell therapy infusions can take place in an inpatient or outpatient care setting, but the patient must be closely monitored at all times.

CAR T-cell therapy can lead to side effects, most notable cytokine release syndrome.

The entire CAR T-cell process lasts approximately one month, not including the recovery time after treatment:

For the first seven days after receiving the CAR T-cell infusion, patients must remain under medical supervision. For weeks 2-4 of the post-infusion timeline, patients must remain within a short drive of their medical facility to respond to any issues.

The total recovery period from CAR T-cell therapy is usually 2-3 months following infusion, according to the Dana-Farber Cancer Institute.

There are several studies for CAR T-cell therapies for cancer. Participating in a clinical trial helps advance cell and gene therapy research and can advance much-needed therapies to more patients in need.

Therapy Insights

Gene induced immunotherapy dominated the market with a revenue share of over 41.9% in 2023. The dominance of the segment can be attributed to research studies aiming to lower the proliferation of various types of cancer by strengthening the immune system. Many gene therapies for cancers are designed on the basis of immunotherapy elements. For instance, PROVENGE (by Dendreon Corporation) is an autologous cellular immunotherapy designed to stimulate a subjects immune system against prostate cancer.

Oncolytic virotherapy is expected to grow at the fastest rate over the forecast period owing to the favorable outcomes and the level of efficacy offered by oncolytic virotherapy. Oncolytic viruses can combat cancer cells without disturbing the healthy cells in vicinity by stimulating natural killer cells. Moreover, there are lucrative research grants for the research on oncolytic virotherapy. For instance, in July 2022, the researchers at the Center for Nuclear Receptors and Cell Signaling at the University of Houston received a USD 1.8 million grant from the National Institutes of Health to work on oncolytic virotherapy.

End-use Insights

Biopharmaceutical companies led the market with a revenue share of over 50.0% in 2023. This is attributed to the increasing global prevalence of different types of cancers owing to various hereditary, environmental, and lifestyle risk factors. Moreover, the market is driven by increasing adoption of elemental gene therapy options by biopharmaceutical giants to design cancer therapeutic regimes. Many novel therapeutic drugs are under different phases of trials and firms are striving to market them in different regions across the globe. For instance, in January 2020, bluebird bio, Inc. launches its drug, ZYNTEGLO in Germany to be used as a one-time gene therapy solution for patients aged 12 years and above.

The biopharmaceutical companies segment is projected to grow at the fastest rate over the forecast period. The increasing global prevalence of malignant tumors is a key factor driving the market. Moreover, an increased interest in oncology therapeutics research and development is resulting in a rise in the number of FDA approvals of gene therapy drugs. For instance, there are 6 FDA-approved cancer gene therapy drugs with Tecratus, Abcema, and Kymriah being the recent approvals.

Recent Developments:

Some of the prominent players in the Cancer gene therapy market include:

Segments Covered in the Report

This report forecasts revenue growth at global, regional, and country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2023 to 2033. For this study, Nova one advisor, Inc. has segmented the global cancer gene therapy market.

Therapy

End-use

By Region

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Excerpt from:
Cancer Gene Therapy Industry is Rising Rapidly Up to USD 18.11 Bn by 2033 - BioSpace

-First efficacy signals demonstrated for a gene therapy under development for Oculopharyngeal Muscular Dystrophy (OPMD) which affects ~15,000 patients worldwide-

- BB-301 facilitated improvements across multiple measures of swallowing function in the first Phase 1b/2a clinical study subject as compared to pretreatment assessments conducted during the observational natural history portion of the study-

-Virtual R&D Day being held today at 9:00 am EDT, details below-

HAYWARD, Calif., April 18, 2024 (GLOBE NEWSWIRE) -- Benitec Biopharma Inc. (NASDAQ: BNTC) (Benitec or Company), a clinical-stage, gene therapy-focused, biotechnology company developing novel genetic medicines based on its proprietary Silence and Replace DNA-directed RNA interference (ddRNAi) platform, today announces positive interim clinical data from the 90-day timepoint following the administration of BB-301 to the studys first subject (Subject 1) treated in the BB-301 Phase 1b/2a single-arm, open-label, sequential, dose-escalation cohort study (NCT06185673) in Oculopharyngeal Muscular Dystrophy (OPMD). BB-301 has been granted Orphan Drug designation by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP).

To date, no clinical studies have systematically demonstrated a clinical improvement in OPMD patients across both objective and subjective measures of swallowing. We are, therefore, pleased to report positive interim clinical data from multiple radiographic measures as well as subject-reported outcome measures from the first subject treated with BB-301, said Jerel A. Banks, M.D., Ph.D., Executive Chairman and Chief Executive Officer of Benitec. We are highly encouraged by these early clinical trial results and for the hope that they may offer to patients and caregivers, and we look forward to reporting additional results and continuing to treat patients as they enter the dosing portion of the study from the Natural History observational lead-in period.

BB-301 Interim Clinical Study Results:

During the OPMD Natural History Study, which represents the pre-dose observational period for each subject, Subject 1 experienced progressive worsening of dysphagia as demonstrated by the results of the videofluoroscopic swallowing studies (VFSS), the cold water timed drinking test, and the key subject-reported outcome measure (the Sydney Swallow Questionnaire). Videofluoroscopic swallowing studies represent the gold standard analytical method for the quantitative assessment of dysphagia (swallowing difficulty) in the clinical setting.

At the 90-day timepoint following the administration of BB-301, Subject 1 demonstrated improvements in key videofluoroscopic assessments which correlated with the observation of similar improvement in the key subject-reported outcome measure as compared to the average values for the respective assessments completed during the pre-dose observational period (as summarized in Figure 1). Notably, the results of many assessments completed at the 90-day timepoint demonstrated improvements over the initial measurements assessed at the subjects first visit for the natural history observational study which occurred more than 12 months prior to the 90-day assessment.

The most significant VFSS improvements at Day 90 were observed for swallowing tasks centered on the evaluation of pharyngeal constrictor muscle function and swallowing efficiency in the context of the consumption of thin liquids, solid foods and thick, non-solid foods (e.g., yogurt or pudding) (Figure 1). The VFSS improvements correlated with an improvement in the key subject-reported outcome measure the Sydney Swallow Questionnaire, indicating an improvement in swallowing function as reported by Subject 1 (Figure 1).

Figure 1: Improvement in All Outcomes at 90-Days Post-BB-301 Injection*

*Company data on file

Regarding the BB-301 safety profile observed to date, no Serious Adverse Events have been observed for the two subjects that have received BB-301. Transient Grade 2 Gastroesophageal Reflux Disease or GERD (i.e., acid reflux or heartburn) was observed for the two subjects that received BB-301. For both subjects, the GERD resolved following the completion of a short course of common prescription medications approved for the treatment of GERD.

OPMD is a rare progressive muscle-wasting disease caused by a mutation in the poly(A)-binding protein nuclear 1 (PABPN1) gene, for which there is currently no effective drug therapy. The disease is characterized by swallowing difficulties (dysphagia), limb weakness and eyelid drooping (ptosis). Dysphagia worsens over time and can lead to chronic choking, regurgitation, aspiration pneumonia, and in severe cases, death. Available clinical and surgical interventions are limited in scope and effectiveness and do not address the underlying progressive muscle weakness.

Virtual R&D Event Information: This live virtual R&D Event, featuring two OPMD key opinion leaders, will be held at 9:00 AM EDT today, April 18th, 2024 and can be accessed here. The event replay will be placed on the News & Events tab on the Investor page of the Benitec website.

About BB-301

BB-301 is a novel, modified AAV9 capsid expressing a unique, single bifunctional construct promoting co-expression of both codon-optimized Poly-A Binding Protein Nuclear-1 (PABPN1) and two small inhibitory RNAs (siRNAs) against mutant PABPN1. The two siRNAs are modeled into microRNA backbones to silence expression of faulty mutant PABPN1, while allowing expression of the codon-optimized PABPN1 to replace the mutant with a functional version of the protein. We believe the silence and replace mechanism of BB-301 is uniquely positioned for the treatment of OPMD by halting mutant expression while providing a functional replacement protein.

About Benitec Biopharma, Inc.

Benitec Biopharma Inc. (Benitec or the Company) is a clinical-stage biotechnology company focused on the advancement of novel genetic medicines with headquarters in Hayward, California. The proprietary Silence and Replace DNA-directed RNA interference platform combines RNA interference, or RNAi, with gene therapy to create medicines that simultaneously facilitate sustained silencing of disease-causing genes and concomitant delivery of wildtype replacement genes following a single administration of the therapeutic construct. The Company is developing Silence and Replace-based therapeutics for chronic and life-threatening human conditions including Oculopharyngeal Muscular Dystrophy (OPMD). A comprehensive overview of the Company can be found on Benitecs website at http://www.benitec.com.

Forward Looking StatementsExcept for the historical information set forth herein, the matters set forth in this press release include forward-looking statements, including statements regarding Benitecs plans to develop and potentially commercialize its product candidates, the timing of completion of pre-clinical and clinical trials, the timing of the availability of data from our clinical trials, the timing and sufficiency of patient enrollment and dosing in clinical trials, the timing of expected regulatory filings, the clinical utility and potential attributes and benefits of ddRNAi and Benitecs product candidates, the intellectual property position, and other forward-looking statements.

These forward-looking statements are based on the Companys current expectations and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments in and risks related to: unanticipated delays; further research and development and the results of clinical trials possibly being unsuccessful or insufficient to meet applicable regulatory standards or warrant continued development; the ability to enroll sufficient numbers of subjects in clinical trials; determinations made by the FDA and other governmental authorities; the Companys ability to protect and enforce its patents and other intellectual property rights; the Companys dependence on its relationships with its collaboration partners and other third parties; the efficacy or safety of the Companys products and the products of the Companys collaboration partners; the acceptance of the Companys products and the products of the Companys collaboration partners in the marketplace; market competition; sales, marketing, manufacturing and distribution requirements; greater than expected expenses; expenses relating to litigation or strategic activities; the Companys ability to satisfy its capital needs through increasing its revenue and obtaining additional financing, given market conditions and other factors, including our capital structure; our ability to continue as a going concern; the length of time over which the Company expects its cash and cash equivalents to be sufficient to execute on its business plan; the impact of the COVID-19 pandemic, the disease caused by the SARS-CoV-2 virus and similar events, which may adversely impact the Companys business and pre-clinical and clinical trials; the impact of local, regional, and national and international economic conditions and events; and other risks detailed from time to time in the Companys reports filed with the Securities and Exchange Commission. The Company disclaims any intent or obligation to update these forward-looking statements.

Investor Relations Contact: Irina Koffler LifeSci Advisors, LLC (917) 734-7387 ikoffler@lifesciadvisors.com

A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/a47d2f41-3feb-49a7-a58f-62e5b0dd4332

Originally posted here:
Benitec Biopharma Reports Positive Interim Clinical Trial Data for First OPMD Subject Treated with BB-301 in Phase 1b ... - GlobeNewswire

A single subretinal dose of a gene therapy was not only well tolerated among patients with neovascular age-related macular degeneration (nAMD), but there was sustained expression of the RGX-314 protein for at least 2 years, showing the potential to control exudation. The results of the phase I/IIa dose escalation trial were published in The Lancet.1

Age-related macular degeneration (AMD) causes vision loss that can turn into partial blindness.

Image credit: Syda Productions - stock.adobe.com

RGX-314, also known as ABBV-RGX-314, is an adeno-associated virus serotype 8 vector that provides potential continuous suppression of VEGF-A. nAMD, also called wet AMD, causes faster vision loss than AMD and, while it doesnt cause complete blindness, can cause patients to lose central vision.2

Real-world outcomes of long-term nAMD treatment have been inferior to those seen in clinical trials because of undertreatment or nonadherence with visits for injections. Therefore, there is strong motivation to develop treatments that provide sustained suppression of VEGF-A, the authors explained.

The open-label, multiple-cohort, multicenter, phase I/IIa, dose-escalation study was conducted at 8 sites in the US with 68 patients. On day 1, all patients received intravitreal ranibizumab. At week 2, 42 who demonstrated the required anatomic response received a subretinal injection of RGX-314. There were 5 different doses being evaluated with 12 patients placed into each cohort based on dosing. The mean (IQR) age at baseline was 80 years (74-85), nearly all (41 of 42) patients were White, and 52% were female.

While all patients experienced at least 1 treatment-emergent adverse event (TEAE), most were grade 1 or 2. The most common TEAEs were postprocedure conjunctival hemorrhage and retinal pigmentary changes. There were also 7 instances of a retinal degeneration event, which were mostly grade 1, typically occurred 6 to 12 months after the gene therapy was administered, and had not resolved at the end of the study.

In 9 of 46 study eyes, reduced visual acuity was reported, although 6 of these were mild or moderate and deemed unrelated to RGX-314. However, the other 3 events were possibly related to the therapy.

The mean baseline best-corrected visual acuity (BCVA) was maintained or improved in 4 of the 5 cohorts, while cohort 1, which received 3x109 genome copies per eye, experienced a gradual reduction in BCVA over time. Patients in cohorts 3 through 5 who did not receive any supplemental antiVEGF-A injections throughout the last year of the study maintained or improved baseline BCVA.

"The publication of the ABBV-RGX-314 Phase I/IIa trial results in The Lancet reinforces the encouraging long-term clinical data observed using subretinal delivery and underscores the potential of ABBV-RGX-314 gene therapy to offer a new approach to the clinical management of wet AMD," Jeffrey S. Heier, MD, director of the Vitreoretinal Service and director of Retina Research at Ophthalmic Consultants of Boston, and primary investigator for the trial, said in a statement.3 "Wet AMD is a chronic, life-long disease and real-world evidence shows patients are losing significant vision over time, and the burden of frequent anti-VEGF injections needed to manage their wet AMD is a major reason why. A single treatment of ABBV-RGX-314 that can potentially provide long-lasting treatment outcomes and a strong safety profile would offer a novel approach to treating this serious and blinding disease."

In an interview4 ahead of the Angiogenesis, Exudation, and Degeneration 2023 meeting, Charles C. Wykoff, MD, PhD, director of research at Retina Consultants of Texas; chair of research, Retina Consultants of America; and deputy chair of ophthalmology for the Blanton Eye Institute, Houston Methodist Hospital; and coauthor on the study, explained that a gene therapy for the most common cause of irreversible blindness would be a tremendous step forward for the opportunity for management of this chronic disease.

He also noted that while gene therapy holds the promise of being one and done, data have shown that some patients do need ongoing therapy.5

"Even if we are using gene therapy, it's important to realize that these patients will continue to need retinal care and retinal follow-up," he said. "You're looking for signs of efficacy, you're monitoring them for safety, you're making sure that they get any retreatments if they need them. Of course, there's a host of other retinal issues that may come up in these patients. They're going to continue to need retina care, certainly, even in the context of gene therapy."

Reference

1. Campochiaro PA, Avery R, Brown DM, et al. Gene therapy for neovascular age-related macular degeneration by subretinal delivery of RGX-314: a phase 1/2a dose-escalation study. Lancet. 2024:S0140-6736(24)00310-6. doi:10.1016/S0140-6736(24)00310-6

2. Age-related macular degeneration. National Eye Institute. June 22, 2021. Accessed April 12, 2024. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration

3. REGENXBIO announces Lancet publication of phase I/IIa study evaluating ABBV-RGX-314 as a one-time gene therapy for wet AMD. REGENXBIO. News release. March 28, 2024. Accessed April 12, 2024. https://regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-announces-lancet-publication-phase-iiia-study

4. Joszt L. Dr Charles Wykoff: gene therapy for wet AMD would be a tremendous opportunity. The American Journal of Managed Care. May 21, 2023. Accessed April 12, 2024. https://www.ajmc.com/view/dr-charles-wykoff-gene-therapy-for-wet-amd-would-be-a-tremendous-opportunity

5. Joszt L. Dr Charles Wykoff discusses gene therapy to treat wet age-related macular degeneration. The American Journal of Managed Care. April 23, 2023. Accessed April 12, 2024. https://www.ajmc.com/view/dr-charles-wykoff-discusses-gene-therapy-to-treat-wet-age-related-macular-degeneration

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Gene Therapy Well Tolerated in Wet AMD, Shows Promise in Visual Acuity - AJMC.com Managed Markets Network

You can add Nov. 16, 2023, to July 16, 1945 the day nuclear power moved from the theoretical to the actual as an entry to the list of consequential moments for everyones favorite vertebrate, Homo sapiens.

The news was easy to miss, but there it was. The United Kingdom announced that it would be the first country in the world to approve the use of gene editing as a medical therapy, starting with two inherited types of anemia: beta-thalassemia, and the more widely known sickle cell anemia. The U.S. Food and Drug Administration (FDA) followed suit three weeks later.

Its official: we humans are going to mess with our DNA, our original blueprints. DNA is the genetic instructions dictating how we look and behave, and that define what diseases we may develop, be prone to or be free of. With our ever-improving gene-editing skills, we are now prepared to peel back the pages of this ancient and sacred text and write the story the way we want to hear it.

DNA makes up the letters of lifes instruction manual for humans or any living thing. Genes organize those letters into words and paragraphs. Chromosomes organize those genes into chapters. In humans, each cell has 23 pairs of chromosomes. Inside the cell, DNA provides the formula for manufacturing specific proteins. Its the blueprint that tells each cell what to build, and how to build it.

Unfortunately, DNA can get altered or damaged, an occurrence thats referred to as a mutation. A mutation can be either inherited or newly acquired. It can cause the gene to produce a faulty product or no product at all. In the case of sickle cell disease, a mutation in the gene that codes for hemoglobin a complex protein that allows red blood cells to shuttle oxygen from the lungs to the body can lead to a whole lot of pain and suffering.

Red blood cells are flexible, allowing them to scooch through tiny capillaries where they unload their oxygen. In sickle cell disease, the mutation in the hemoglobin molecule can cause a red blood cell to change shape from a circle to a sickle. Sickled red blood cells lack flexibility, so they plug up the very capillaries they were supposed to be sliding through. Just as a traffic accident can lead to a pileup of cars behind it, one stuck sickled cell can trigger an upstream backup of stuck sickled cells.

Traffic jams are a pain, but a sickle cell attack aptly termed a crisis produces a deep, aching pain that may be unrivaled in human suffering. As capillaries and small arteries plug up, downstream tissues are left without oxygen. These blood-starved tissues begin screaming for oxygen as if their lives depended on it which they do.

Although a sickle cell crisis can cause excruciating pain, thankfully it is only rarely lethal. With pain medications, intravenous fluids, blood transfusions and oxygen support, the pain eventually eases. But repeated episodes take their toll on the body, significantly shortening the life expectancy of those with the disease.

Those with sickle cell disease (SCD) carry two copies of a sickling-prone hemoglobin gene (HbS). One copy comes from each parent. Those with sickle cell trait (SCT) have just one copy of HbS, but thats not enough to cause sickling except in rare circumstances like scuba diving or mountain climbing.

The sickle cell gene seems to have originated in sub-Saharan Africa, where having a single copy of the gene having SCT protects against severe malaria infections. Thats because the parasite that causes malaria, which reproduces by infecting red blood cells, has a harder time doing that inside cells carrying a lone sickle gene.

Although the prevalence of the sickle cell gene remains highest in sub-Saharan Africa, slavery and migration patterns have expanded its global range, so that today SCD can affect people of Hispanic, Southern European, Middle Eastern or Asian Indian backgrounds.

In the United States, 7% to 8% of Black newborns carry the sickle cell trait. In addition, 0.7% of Hispanic newborns, 0.3% of white newborns, and 0.2% of Asian or Pacific Islander newborns carry the trait. One out of every 365 Black newborns will have SCD. In total, about 100,000 people in the U.S. and 20 million people worldwide have SCD. Thats a lot of people hoping for a cure.

Casgevy is the first FDA-approved therapy to use CRISPR gene-editing technology. CRISPR is an acronym we can all be grateful for because it eliminates a phrase we will never be able to remember: clustered regularly interspaced short palindromic repeats.

In the case of Casgevy, CRISPR is used to create a line of red blood cells that manufacture hemoglobin F (HbF) thats F as in fetus. HbF has stronger oxygen-binding characteristics than adult hemoglobin (HbA). Thats because in the womb humans are breathing through the mothers placenta, and not through the lungs, which are filled with amniotic fluid. HbF production typically gets turned off soon after birth. Thats unfortunate for those with sickle cell disease who carry HbS, not HbA because HbF helps prevent sickling.

Casgevy turns HbF production back on.

Lyfgenia works by giving people with sickle cell disease a line of blood cells that can manufacture a form of adult hemoglobin (HbA).

Neither Casgevy nor Lyfgenia completely eliminates sickle cells, but they dilute the concentration of sickle-prone cells, thereby preventing sickle cell crises.

No surprise treatment with Casgevy and Lyfgenia is more complicated than what I just described. It requires removing stem cells from the blood. Stem cells are a little like the queen bee in a hive: They produce all the cells that will keep the body vigorous and healthy. In this application, the stem cells of interest are the ones that manufacture the new red blood cells needed to replace those at the end of their 120-day life span (or 20 to 30 days for fragile sickle cells). After these blood stem cells are removed and sent to the lab for gene therapy, the patient is given chemotherapy to decrease the number of stem cells making sickled red blood cells. This makes room for the new-and-improved stem cells.

Chemotherapy comes in a variety of potencies, and in this case, its fairly potent the kind you need to be in the hospital for. Following the gene therapy infusion, itll be 3 to 6 more weeks in the hospital waiting for the body to recover from the chemotherapy and for the modified stem cells to start growing back in serious numbers.

Like nuclear power or artificial intelligence, the technology of gene therapy brings great promise but also serious risks and ethical concerns.

There are the risks of the treatment itself: Did the gene therapy get inserted into the right gene location, and is it functioning correctly? Or did it end up in the wrong spot, altering the function of genes that we meant to leave alone?

There is the ethical question of who will get stem cell therapy. The medical complexity and steep cost of stem cell therapy a cool $2.2 million for a Casgevy treatment, and $3.1 million for Lyfgenia make it a boutique item only the haves will be able to afford.

And there are the ethics of how and where we will apply the technology. Although history teaches us that H. sapiens is an inventive and curious creature, we also are a never-quite-satisfied, boundary-pushing and occasionally nefarious lot. While were using gene therapy to eliminate sickle cell disease or perhaps someday Alzheimers, cardiovascular disease or what have you someone is going to ask: Whats the harm in getting rid of things like nearsightedness, balding, belly fat, wrinkles? And while were at it, why not use gene therapy to make sure we or our offspring have what it takes to compete in the NBA or the Ivy League, Hollywood or the Navy Seals? And can we eliminate dying?

Dont think we humans will go there? Comedian and futurist Jon Stewart told Stephen Colbert he sees it going this way: The world ends. The last words man utters are somewhere in a lab. A guy goes, Huh-huh. It worked!

Scientists disagree on whether Stewart was joking but recommend further research.

Relevant reading

When Winter Came

Dr. Pierre Sartor wrote an inspiring first-person account of how he treated more than 1,000 patients and by his reckoning, lost only five which lay forgotten in a lockbox of family artifacts until it was discovered decades later by his granddaughter, Beth Obermeyer, a journalist and author of

Read the original here:
Messing with the blueprints: Gene therapy has arrived - Mayo Clinic Press

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Excerpt from:
Adeno-associated virus as a delivery vector for gene therapy of human diseases | Signal Transduction and Targeted ... - Nature.com

According to the latest research by nova one advisor, the global cell and gene therapy market size was valued at USD 18.13 billion in 2023 and is anticipated to reach around USD 97.33 billion by 2033, growing at a CAGR of 18.3% from 2024 to 2033.

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The cell and gene therapy market provides therapeutic solutions related to genes and cells. The market deals with research & development, testing, production, and distribution of products and treatment procedures related to genes and cells. Hospitals, research laboratories, pharmaceutical companies, pharmacies, research institutions, and universities are involved in delivering the applications associated with gene and cell therapies. Gene and cell therapies are developed to prevent, treat, or potentially cure numerous diseases. The potential of these therapies to cure, treat, or prevent diseases that are life-threatening increases the demand and boosts the growth of the market. Gene and cell therapies are used in blood stem cell transplantation, gene editing, engineering of the immune system, tissue regeneration, in-vivo gene transfer, cancer treatment, and treatment of different disorders. These therapies can provide better results and enhance quality of life.

North America dominated the cell and gene therapy market in 2023. North America is a developed region that has developed healthcare and research infrastructure, better facilities, and government support that boosts the growth of the market. Governments in the North American region have a huge national budget for healthcare and research. Countries like the U.S. and Canada contribute to the growth of the market in the North American region. As of now, the FDA has approved 37 products for gene and cell therapy. The U.S. has the American Society of Gene & Cell Therapy (ASGCT) for professionals, scientists, physicians, and patient advocates that help advance knowledge, education, and awareness for discovering and developing clinical applications of gene and cell therapy.

The Canadian government is also focusing on improving health with the help of genes and therapies and is launching various programs to help with this. The government launched Disruptive Technology Solutions, which will help tackle the challenges associated with gene and cell therapies. The treatment procedures will be done to cure rare genetic disorders and chronic diseases.

Key Takeaways:

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The cell and gene therapy market is exploding globally

Ground-breaking developments in next-generation cell and gene therapies (CGTs) offer curative value for patients with few to no other therapeutic interventions for either maintenance or cure within specific disease areas, many of which include rare and ultra-rare diseases.The largest therapeutic area is cancer, followed by musculoskeletal diseases and eye diseases.Multiple approved products have been launched in global markets and the number of clinical trials continues to grow. In Europe, these therapies are classified under Advanced Therapeutic Medicinal Products (ATMPs) and are driven by a diverse set of scientific advancements including CAR-T, TCR-T, stem cells, siRNA, oligonucleotides, gene editing (CRISPR, Zinc Fingers, TALENs) and viral transfection.

The global CGT market is projected to grow at a compound annual growth rate of over 36 percent from 2019-2025, to ~ 10 billion. With more than 900 companies globally focusing on CGTS and over 1,000 clinical trials being conducted, the industry could see numerous approvalsas many as 10 to 20 new advanced therapies per year starting in 2025. Moreover, 33% of these clinical trials is being conducted in Europe.1

Global biopharma companies as well as smaller, venture backed-up start-ups are rapidly investing in this complex space. In 2018, about $13 billion has been invested globally in advanced therapies such as cell, gene and gene modifying therapies. In 2019, 19 CGT-related M&A deals worth over $156 billion were completed.

As with any innovative and disruptive technology, CGT developers face challenges along several key stages of the product life cycle. Compared to chemical-based pharmaceuticals, key success factors such as enabling patient access, managing supply chain and manufacturing operations, evidencing compliance with increasingly complex regulatory requirements and alternate business models impose a greater burden.

Segments Insights:

By Therapy Insights

The market for cell and gene treatments consists of companies (organizations, sole proprietors, and partnerships) that sell the therapies they have developed. Cell therapy is the transfer of whole, living cells derived from allogeneic or autologous sources, while gene therapy is the introduction, deletion, or alteration of the genome to treat disease. The market is made up of the money that businesses creating goods for cell and gene therapy make from the sales of those items.

Cell treatment and gene therapy are the two primary product categories in this field. Gene therapy is a field of medicine that focuses on altering cells' genetic make-up to treat disease or reverse it by repairing or replacing genetic material that has been damaged. Oncology, dermatological, musculoskeletal, and other applications are among the many that are used in hospitals, ambulatory surgery centers, cancer treatment facilities, wound care facilities, and other industries.

Cell & Gene Therapy Market Revenue, By Therapy Type, 2022-2032 (USD Million)

By Therapy Type

2022

2023

2027

2031

2032

Cell Therapy

13,396.01

15,621.48

29,433.95

57,138.21

67,757.69

Gene Therapy

2,067.97

2,502.14

5,406.11

11,864.27

14,480.51

By Therapeutic class

Based on application, the market is divided into cardiovascular disease, cancer, genetic disorder, rare diseases, oncology, hematology, ophthalmology, infectious disease, neurological disorders. Among these, the infectious disease segment dominates the market in 2023. The oncological disorder segment held a revenue share of 13.53% in 2023. Research and treatment in the biomedical domains of cell therapy and gene therapy. Both treatments have the ability to lessen the underlying cause of hereditary disorders and acquired diseases. Both therapies aim to treat, prevent, or perhaps cure diseases. By repairing or changing specific cell types, or by employing cells to transport a medication across the body, cell therapy tries to treat diseases. Cell therapy involves growing or modifying cells outside of the body before injecting them into the patient. The cells may come from a donor (allogeneic cells) or the patient (autologous cells)6. By replacing, deactivating, or introducing genes into cells, either inside the body (in vivo) or outside the body, gene therapy seeks to treat disorders (ex vivo).

The market for genetic disorders is expanding as a result of factors like the high prevalence of genetic and chronic disease cases and the growing government initiatives to raise public knowledge of genetic testing and diagnosis. Researchers are developing novel techniques for screening, diagnosing, and treating patients for a variety of cardiac diseases as they investigate the genetic roots of heart and vascular illness. Some researchers are looking for new ways to nine patients who are at risk for sudden cardiac death. Others are examining how medicines that could postpone or obviate the need for cardiac surgery could benefit patients with uncommon illnesses.

The intricacy of mitochondrial genetics and the diverse clinical and biochemical symptoms of primary mitochondrial disorders (PMDs) have shown to be a significant obstacle to the development of effective disease-modifying medications. A successful clinical transition of genetic medicines for PMDs is possible, according to encouraging evidence from gene therapy trials in patients with Leber hereditary optic neuropathy and improvements in DNA editing tools.

Cell & Gene Therapy Market Revenue, By Therapeutic Class, 2022-2032 (USD Million)

By Therapeutic Class

2022

2023

2027

2031

2032

Cardiovascular Disease

744.36

882.84

1,780.08

3,697.84

4,460.03

Genetic Disorder

1,643.41

1,922.21

3,665.70

7,202.20

8,566.52

Oncology

1,936.87

2,272.26

4,385.58

8,720.66

10,403.81

Hematology

1,196.56

1,396.75

2,642.34

5,150.06

6,113.36

Ophthalmology

835.60

972.46

1,817.62

3,500.15

4,142.33

Infectious Disease

4,420.18

5,206.30

10,210.05

20,628.98

24,708.86

Neurological Disorders

658.61

777.29

1,536.51

3,129.23

3,755.58

Others

4,028.39

4,693.50

8,802.17

16,973.35

20,087.70

By Delivery Method

The market is split into In Vivo therapy and Ex Vivo therapy according to the type of therapy. In vivo therapy market is anticipated to grow exponentially throughout the projected period. When it comes to gene therapy, there are two different methods: ex vivo and in vivo, setting aside cell therapies. The altered human gene must first enter the diseased person's cells for gene therapy to take effect. There are two methods for doing this; Genetic material is supplied in vivo to afflicted cells (cancer cells or other cells) that are still present within an individual's body. After cells are collected and exposed to the genome in Ex vivo, altered genes are transferred to a person's body.

See the original post:
Cell and Gene Therapy Market Size to Reach USD 97.33 Bn by 2033 - BioSpace

In a recent review published in Signal Transduction and Targeted Therapy, researchers presented recombinant adeno-associated virus (rAAV)-based genetic applications to treat human diseases.

Study:Adeno-associated virus as a delivery vector for gene therapy of human diseases. Image Credit:Gorodenkoff/Shutterstock.com

Adeno-associated virus (AAV) is a crucial component of clinical gene therapy due to its low pathogenicity and capacity to generate long-term gene expression in various tissues. Recombinant AAV (rAAV) is designed to increase specificity and can cure several illnesses.

However, concerns persist concerning the safety of high-dose viral therapy in people, as well as immune responses and side effects. Researchers prefer AAV vectors due to their broad tissue tropism, high safety profile, and adaptability in manufacturing procedures.

In the present review, researchers explored AAV-vectored genetic treatment of human disorders.

AAV-1, 4, and 7,8 originate from non-human primates (NHP), while AAV-2, 3, 5, 6, and 9 originate from humans. Primary receptors for cellular attachment include N-linked sialic acid, O-linked sialic acid, HSPG, and galactose.

Co-receptors for cellular attachment include fibroblast growth factor receptor 1 (FGFR1), hepatocyte growth factor receptor (HGFR), laminin receptor (LamR), a cluster of differentiation 9 (CD9), tetraspanin, platelet-derived growth factor receptor (PDGFR), and epidermal growth factor receptor (EGFR).

Receptors for post-attachment for AAVs include the adeno-associated virus receptor (AAVR) and G protein-coupled receptor 108 (GPR108).

AAVs localize in the skeletal muscle, central nervous system (CNS), lungs, retina, liver, pancreas, kidney, and heart.

Natural AAV mutants are isolated from non-human primates and humans using high-cycle polymerase chain reaction (PCR) with high-throughput genetic sequencing. Rational design entails altering amino acid molecules in AAV capsids to boost transduction capabilities or elude immune surveillance.

The directed evolution engineering strategy is used to create unique AAV variations with specificity. In silico techniques, known as AAV capsid sequences, they are used to rebuild ancestral sequences of the virus.

Machine learning uses mutagenized AAV-transduced data to predict the link between AAV genome sequences, packing capacities, and site tropism.

Viral infection and transfection platforms are primarily used to manufacture rAAVs. Plasmid temporary transfection of the human embryonic kidney 293 (HEK293) cell lines continues to be the most often used approach; however, stable cellular lines and systems using baculovirus (BV) or herpes simplex virus (HSV) provide scalable options for scalable manufacturing.

TESSA, a transfection-free system of helper viruses, was designed to generate high-yield recombinant AAVs.

All-in-one producer cells that can be induced pharmaceutically might be the best production platform to obtain recombinant AAV-based pharmaceuticals in the future.

Recombinant AAV gene therapy is effective in treating a wide range of human diseases, including ocular (X-linked retinoschisis pigmentosa, choroideremia, Leber hereditary optic neuropathy), neurological (Alzheimers disease, Parkinsons disease, Huntingtons disease), metabolic (glycogen storage disease, mucopolysaccharidosis, Pompe disease, and Fabry disease), hematological (Hemophilia A, B), neuromuscular (Duchenne muscular dystrophy), cardiovascular (ischemic cardiomyopathy, dilated cardiomyopathy, and congestive heart failure), and gastric cancer.

The ocular immune-privileged condition and tiny volume make it ideal for gene therapy, with various delivery options available. FDA-approved rAAV gene treatments for neurological diseases employ stereotactic, physically limited delivery or extensive CNS transduction by intravenous (IV) administration.

In cellular hematologic circumstances, bone marrow stem cells dilute the rAAV genome, releasing acellular components into the circulation. Recombinant AAV has shown promise in preclinical cancer investigations, but its application to individuals is restricted.

Anti-tumor techniques based on rAAV provide advantages such as regulating or inhibiting gene expression.

Delivery routes determine the performance of rAAV capsids, including intravascular, direct intra-tissue injection, and distribution into pre-existing body cavities or fluid spaces. Each route and capsid is selected based on the ailment, target location, organ system, and patient age.

Intravascular injection enables extensive transduction, although large dosages are necessary. The intra-tissue injection is invasive and confined, whereas intra-cavity administration is distributed in an already established space but may be limited. Intra-fluid delivery has drawbacks, including long vector transit distances.

Recombinant AAV administration, including serotypes, promoters, and enhancers, can cause side effects such as genotoxicity, carcinogenesis, liver damage, thrombotic microangiopathy, and microvascular thrombosis.

Intravenous administration can result in hepatotoxicity, increased liver enzymes, and drug-induced liver damage. Intravenous treatment may result in dorsal root ganglion toxicity, immune cell infiltration, and nerve cell body degeneration.

Edema, inflammation, gliosis, and immunological infiltration are observed on brain magnetic resonance imaging (MRI) scans following intrathecal and intraparenchymal rAAV injections.

The review highlights rAAV-based gene therapy applications for human illnesses. Early success in treating monogenic disorders demonstrated its safety and efficacy.

Challenges include effective delivery, overcoming physical constraints, and understanding rAAV immunogenicity. Strategies for regulating immune responses are critical for patient safety.

Understanding rAAV integration aids in predicting tumor growth, hepatotoxicity, neurotoxicity, and adverse consequences. Further research could assess vector immunogenicity, dosage optimization, and long-term safety.

View original post here:
Adeno-associated virus: The gene therapy revolution faces manufacturing and safety hurdles - News-Medical.Net

Advances in the treatment of ophthalmic conditions with gene therapies have led to a growing market with huge potential for the future, according to research from DelveInsight.

The industry analyst has prepared a reportindicating that the market size for gene therapies in ophthalmology reached roughly $132 million across mature markets last year.

Taking into account new therapies expected to come online in future years, this market could grow at

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Research shows stellar growth for gene therapies in ophthalmology - The Pharma Letter

A company started by University of Pennsylvania scientist Jim Wilson has received FDA approval to test a form of gene editing in infants for the first time in the United States, the company said Thursday.

The Plymouth Meeting company, iECURE, is developing a treatment for babies whose livers are unable to make a crucial enzyme.

Infants born with a severe form of the illness can lapse into a coma within a day or two of birth, their brains damaged by a buildup of ammonia. Some die soon thereafter; the rest have little recourse beyond a liver transplant.

This is the same disease that Wilson was studying in a high-profile test that resulted in a patient death in 1999. The patient in that case, Jesse Gelsinger, had a mild form of the disease. The 18-year-old died after his body rejected the virus used to deliver the treatment.

In Wilsons new approach with iECURE, the gene is delivered with a different type of virus that does not trigger the immune system a delivery method that he already has licensed for use in several other drugs.

The treatment had previously been approved for testing in the United Kingdom and Australia, iECURE said. The company is enrolling boys up to 9 months old.

This milestone is the culmination of over 8 years of pre-clinical research in my laboratory addressing gene editing strategies for severe rare liver metabolic diseases, Wilson said in a news release.

Founded in 2022, iECURE raised $65 million from venture capitalists in late 2022. That was during a period of waning investor enthusiasm for cell and gene therapy companies.

Both Penn and Wilson have an unspecified financial interest in iECURE.

See original here:
Penn scientist Jim Wilson's iECURE can start testing gene therapy in infants - The Philadelphia Inquirer

Sekar Kathiresan, MD Credit: Verve Therapeutics

Verve Therapeutics announced it would be halting enrollment in its Heart-1 trial following an adverse event in the trials 6th patient dosed with VERVE-101 0.45 mg/kg dose and subsequent consultation with the independent data safety and monitoring Board.

Announced by Verve Therapeutics on April 2, 2024, the press release indicates the patient experienced a Grade 3 drug-induced transient increase in ALT a d a Grade 3 drug-induced thrombocytopenia within the first 4 days after dosing with the 0.45 mg/kg dose of VERVE-101. A decision that comes less than 5 months after the phase 1b trial stole headlines alongside SELECT and other late-breakers at the American Heart Associations Scientific Sessions 2023, the company now intends to prioritize the development of VERVE-102 and the initiation of the Heart-2 clinical trial.1,2

The Heart-1 study continues to support proof-of-concept forin vivobase editing of thePCSK9gene in the liver, with a meaningful and durable lowering of LDL-C, said Sekar Kathiresan, MD, co-founder and chief executive officer of Verve Therapeutics.1 However, at potentially therapeutic dose levels of VERVE-101, we have observed certain asymptomatic laboratory abnormalities, which we believe are attributable to the LNP delivery system. The safety of patients in our clinical trials is of the utmost importance. We plan to further investigate the laboratory abnormalities observed in the Heart-1 study in order to inform the next steps for VERVE-101.

At AHA 2023, Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, presented interim data from the heart-1 trial. A first-in-human trial of patients with heterozygous familial hypercholesterolemia (HeFH), Bellinger presented data from 10 participants across 4 dose cohorts: 0.1 mg/kg (n = 3), 0.3 mg/kg (n = 3), 0.45 mg/kg (n = 3), and 0.6 mg/kg (n = 1). With a data cutoff of October 16, 2023, results of the trial pointed to an LDL-C reduction of 55% with just a single treatment at the greatest dose.2

In their April 02, 2024 announcement, Verve Therapeutics underlined all safety events were reported to regulatory agencies in the US, New Zealand, and the UK. The company pointed out theInvestigational New Drug Application and other CTAs for VERVE-101 remain active at this time.1

Of note, the patient did not experience any bleeding or other symptoms related to the aforementioned abnormalities and the abnormalities full resolved within a few days.1

Like VERVE-101, VERVE-102 leverages a the same base editor and guide RNA for PCSK9, but uses a different lipid nanoparticle delivery system. Verve Therapeutics highlighted 2 key differences in the therapies in their release:1

Verve Therapeutics highlighted receipt of regulatory clearances for the Heart-2 trial, which will include patients with HeFH or premature coronary artery disease, in the UK and Canada, with plans to launch the trial in Q2 2024.1

At this time, we are prioritizing the initiation of the Heart-2 clinical trial of VERVE-102 due to its proximity to the clinic and its use of a different LNP that incorporates an ionizable lipid which has been well-tolerated in third-party clinical trials, Kathiresan said.1 We are grateful to our study participants and to our investigators, who share our belief in the promise of single-course gene editing medicines for the treatment of cardiovascular disease. We look forward to initiating the Heart-2 trial in the second quarter of this year.

References:

Originally posted here:
Verve Therapeutics Halts Enrollment of Heart-1 PCSK9 Gene Therapy Trial - MD Magazine

The concept of putting genes into the human body to correct a missing or dysfunctional gene first emerged in the 1960s. Since then, the field of gene therapy has experienced groundbreaking research discoveries, tragic pitfalls, and finally, a resurgence in interest and a rise in breakthroughs.

Download this Science Milestone from Drug Discovery News to learn about the complicated past of early gene therapy discoveries and the technologies that eventually led to gene therapy success.

Original post:
Science Milestone: The evolution of gene therapy - Drug Discovery News

Researchers have shown that dangerous cysts, which form over time in polycystic kidney disease (PKD), can be prevented by a single normal copy of a defective gene. This means the potential exists that scientists could one day tailor a gene therapy to treat the disease. They also discovered that a type of drug, known as a glycoside, can sidestep the effects of the defective gene in PKD. The discoveries could set the stage for new therapeutic approaches to treating PKD, which affects millions worldwide. The study, partially funded by the National Institutes of Health (NIH), is published in Cell Stem Cell.

Scientists used gene editing and 3-D human cell models known as organoids to study the genetics of PKD, which is a life-threatening, inherited kidney disorder in which a gene defect causes microscopic tubes in the kidneys to expand like water balloons, forming cysts over decades. The cysts can crowd out healthy tissue, leading to kidney function problems and kidney failure. Most people with PKD are born with one healthy gene copy and one defective gene copy in their cells.

Human PKD has been so difficult to study because cysts take years and decades to form. This new platform finally gives us a model to study the genetics of the disease and hopefully start to provide answers to the millions affected by this disease."

Benjamin Freedman, Ph.D., senior study authorat the University of Washington, Seattle

To better understand the genetic reasons cysts form in PKD, Freedman and his colleagues sought to determine if 3-D human mini-kidney organoids with one normal gene copy and one defective copy would form cysts. They grew organoids, which can mimic features of an organ's structure and function, from induced pluripotent stem cells, which can become any kind of cell in the body.

To generate organoids containing clinically relevant mutations, the researchers used a gene editing technique called base editing to create mutations in certain locations on the PKD1 and PKD2 genes in human stem cells. They focused on four types of mutations in these genes that are known to cause PKD by disrupting the production of polycystin protein. Disruptions in two types of the protein polycystin-1 and polycystin-2 are associated with the most severe forms of PKD.

They then compared cells with two gene copy mutations in organoids to cells with only one gene copy mutation. In some cases, they also used gene editing to correct mutations in one of the two gene copies to see how this affected cyst formation. They found organoids with two defective gene copies always produced cysts and those that carried one good gene copy and one bad copy did not form cysts.

"We didn't know if having a gene mutation in only one gene copy is enough to cause PKD, or if a second factor, such as another mutation or acute kidney injury was necessary," Freedman said. "It's unclear what such a trigger would look like, and until now, we haven't had a good experimental model for human PKD."

According to Freedman, the cells with one healthy gene copy make only half the normal amount of polycystin-1 or polycystin-2, but that was sufficient to prevent cysts from developing. He added that the results suggest the need for a second trigger and that preventing that second hit might be able to prevent the disease.

The organoid models also provided the first opportunity to study the effectiveness of a class of drugs known as eukaryotic ribosomal selective glycoside on PKD cyst formation.

"These compounds will only work on single base pair mutations, which are commonly seen in PKD patients," explained Freedman. "They wouldn't be expected to work on any mouse models and didn't work in our previous organoid models of PKD. We needed to create that type of mutation in an experimental model to test the drugs."

Freedman's team found that the drugs could restore the ability of genes to make polycystin, increasing the levels of polycystin-1 to 50% and preventing cysts from forming. Even after cysts had formed, adding the drugs slowed their growth.

Freedman suggested that a next step would be to test existing glycoside drugs in patients. Researchers also could explore the use of gene therapy as a treatment for PKD.

The research was supported by NIH's Nation Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, and National Institute of General Medical Sciences through awards R01DK117914, UH3TR002158, UH3TR003288, U01DK127553, U01AI176460, U2CTR004867, UC2DK126006, P30DK089507, R21DK128638, and R35GM142902; an Eloxx Pharmaceuticals Award; the Lara Nowak-Macklin Research Fund; and a Washington Research Foundation fellowship.

Source:

Journal reference:

Vishy, C. E.,et al.(2024) Genetics of cystogenesis in base-edited human organoids reveal therapeutic strategies for polycystic kidney disease. Cell Stem Cell. doi.org/10.1016/j.stem.2024.03.005.

Read the original:
Gene therapy and glycoside drugs offer new hope for polycystic kidney disease treatment - News-Medical.Net

Jeffrey S. Heier, MD

Credit: Ophthalmic Consultants of Boston

Subretinal delivery of ABBV-RGX-314, a potential one-time gene therapy, was well-tolerated, with no clinically recognized immune response, in the treatment of neovascular (wet) age-related macular degeneration (nAMD), according to phase 1/2a results published in The Lancet.1

The publication detailed two-year data suggesting the novel approach of RGX-314 for sustained vascular endothelial growth factor (VEGF)-A suppression, with the potential to safely maintain vision and reduce treatment burden in patients with nAMD after a single dose.

Wet AMD is a chronic, life-long disease and real-world evidence shows patients are losing significant vision over time, and the burden of frequent anti-VEGF injections needed to manage their wet AMD is a major reason why, Jeffrey S. Heier, MD, director of the vitreoretinal service and retina research, Ophthalmic Consultants of Boston and the primary study investigator, said in a statement.2 A single treatment of ABBV-RGX-314 that can potentially provide long-lasting treatment outcomes and a strong safety profile would offer a novel approach to treating this serious and blinding disease.

Frequent anti-VEGF-A injections lessen the risk of rapid, severe vision loss among patients with nAMD, but the frequency-related burden could lead to undertreatment, and thus, vision loss over time.3 Sustained suppression of the VEGF-A pathway may provide the maintenance of vision and a reduction in the associated treatment burden.

RGX-314, an adeno-associated virus serotype 8 vector expressing an anti-VEGF-A antigen-binding fragment, is developed to allow continuous VEGF-A suppression after a single administration.2 REGENXBIO is investigating two separate routes of administration of RGX-314 to the eye, including standard subretinal delivery and suprachoroidal delivery.

Current results from the phase 1/2a, open-label, dose-escalation study reported the safety and efficacy of the subretinal delivery of five dose cohorts of RGX-314 for patients with nAMD.1 Between May 2017 and May 2019, investigators screened 110 patients with previously treated nAMD for eligibility criteria. The trials primary outcome was the safety of RGX-314 delivered by subretinal injection up to week 26.

After enrolling 68 individuals into the trial, 42 participants met the required anatomic response to intravitreal ranibizumab and received a single RGX-314 injection (dose range 3x109 to 2.5x1011 genome copies per eye). Participants were observed 1 day and 1 week after administration, then monthly for 2 years.

Analyses revealed 20 serious adverse events in 13 participants, with one event considered potentially related to RGX-314. The event was pigmentary changes in the macular with severe vision reduction 12 months after injection of RGX-314 at a dose of 2.5 x 1011 genome copies per eye.

Heier and colleagues observed asymptomatic pigmentary changes in the inferior retinal periphery months after subretinal RGX-314, primarily at doses of 6x1010 genome copies per eye or higher. In addition, the analysis demonstrated no clinically determined immune responses or inflammation outside of those expected after routine vitrectomy.

Overall, the doses of 6 x 1010 genome copies per eye or higher led to sustained concentrations of RGX-314 protein in the aqueous humor, as well as stable or improved BCVA and central retinal thickness, with little to no supplemental anti-VEGF injections administered in most participants.

Heier and colleagues noted these results inform the pivotal program to assess RGX-314 for the treatment of nAMD further. Two pivotal trials, ATMOSPHERE and ASCENT, are currently evaluating RGX-314 in patients with wet AMD with on-target enrollment.

RegenXBio expects these data to support regulatory submission with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in late 2025 through early 2026.2

To have these Phase I/IIa data published in The Lancet highlights the groundbreaking work of our scientists and investigators, and further validates the clinically transformative nature of ABBV-RGX-314 as a potential one-time gene therapy for wet AMD that may help patients maintain or improve their vision, Kenneth T. Mills, president and chief executive officer of REGENXBIO, added in a statement.2

References

Link:
RGX-314 Gene Therapy for nAMD Well-Tolerated in Phase 1/2a Study - MD Magazine

Co-author Steven Gray, Ph.D., is Associate Professor of Pediatrics, Molecular Biology, Neurology, and in the Eugene McDermott Center for Human Growth and Development at UTSouthwestern.

DALLAS March27, 2024 A gene therapy developed by researchers at UTSouthwestern Medical Center for a rare disease called giant axonal neuropathy (GAN) was well tolerated in pediatric patients and showed clear benefits, a new study reports. Findings from the phase one clinical trial, published in the New England Journal of Medicine, could offer hope for patients with this rare condition and a host of other neurological diseases.

This trial was the first of its kind, for any disease, using an approach to broadly deliver a therapeutic gene to the brain and spinal cord by an intrathecal injection, said co-author Steven Gray, Ph.D., Associate Professor of Pediatrics, Molecular Biology, Neurology, and in the Eugene McDermott Center for Human Growth and Development at UTSouthwestern. Even with the relatively few patients in the study, there were clear and statistically significant benefits demonstrated in patients that persisted for years.

Dr. Gray developed this gene therapy with co-author Rachel Bailey, Ph.D., Assistant Professor in the Center for Alzheimers and Neurodegenerative Diseases and of Pediatrics at UTSW.Dr. Gray is an Investigator in thePeter ODonnell Jr. Brain Institute.

GAN is extraordinarily rare, affecting only about 75 known families worldwide. The disease is caused by mutations in a gene that codes for a protein called gigaxonin. Without normal gigaxonin, axons the long extensions of nerve cells swell and eventually degenerate, leading to cell death. The disease is progressive, typically starting within the first few years of a childs life with symptoms including clumsiness and muscle weakness. Patients later lose the ability to walk and feel sensations in their arms and legs, and many gradually lose hearing and sight and die by young adulthood.

In the clinical trial conducted at the National Institutes of Health (NIH), Drs. Gray and Bailey worked with colleagues from the National Institute of Neurological Disorders and Stroke (NINDS) to administer the therapy to 14 GAN patients from 6 to 14 years old. Using a technique they developed to package the gene for gigaxonin into a virus called adeno-associated virus 9 (AAV-9), the researchers injected it into the intrathecal space between the spinal cord and the thin, strong membrane that protects it. Tested for the first time for any disease, this approach enabled the virus to infect nerve cells in the spinal cord and brain to produce gigaxonin in nerve cells, allowing them to heal the cells axons, which grow throughout the body.

Amanda Grube, 14, one of the trial's participants, has seen improvement in her diaphragm and other muscles associated with breathing, her mother says. However, many of Amanda's other functions, including her mobility, did not benefit. (Photo credit: McKee family)

After one injection, the researchers followed the patients over a median of nearly six years to determine whether the treatment was safe and effective. Only one serious adverse event was linked to the treatment fever and vomiting that resolved in two days suggesting it was safe. Over time, some patients showed significant recovery on an assessment of motor function. Other measurements revealed that several of the patients improved in how their nerves transmitted electrical signals.

One of the trials participants, 14-year-old Amanda Grube, has experienced improvement in her diaphragm and other muscles associated with breathing, according to her mother, Katherine McKee. However, many of Amandas other functions did not benefit including her mobility.

Thats why I hope theres more to come from the research that can help patients even more,Mrs. McKee said. Amanda has dreams and ambitions. She wants to work with animals, save the homeless, and design clothes for people with disabilities.

Dr. Gray said that in many ways, the study offers a road map to carry out similar types of clinical trials. The findings have broader implications because this study established a general gene therapy treatment approach that is already being applied to dozens more diseases, he said.

Although the phase one results are promising, Dr. Gray said he and other researchers will continue to fine-tune the treatment to improve results in future GAN clinical trials. He is also using this method for delivering gene therapies to treat other neurological diseases at UTSW, where he is Director of the Translational Gene Therapy Core, and at Childrens Health. Work in theGray Labhas already led to clinical trials for diseases including CLN1 Batten disease, CLN5 Batten disease, CLN7 Batten disease, GM2 gangliosidosis, spastic paraplegia type 50, and Rett syndrome.

The GAN study was funded by the National Institute of Neurological Disorders and Stroke (NINDS), Division of Intramural Research, NIH; Hannahs Hope Fund; Taysha Gene Therapies; and Bamboo Therapeutics-Pfizer.

Drs. Bailey and Gray are entitled to royalties from Taysha Gene Therapies. Dr. Gray has also consulted for Taysha and serves as Chief Scientific Adviser.

About UTSouthwestern Medical Center

UTSouthwestern, one of the nations premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institutions faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 21 members of the National Academy of Medicine, and 13 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,100 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UTSouthwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.

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Gene therapy offers hope for giant axonal neuropathy patients - UT Southwestern

According to latest study, the global advanced therapy medicinal products CDMO Market size was valued at USD 6.10 billion in 2023 and is projected to reach USD 34.53 billion by 2033, growing at a CAGR of 18.93% from 2024 to 2033.

Key Takeaways:

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owing to risingclinical trialsfor advanced therapy medicinal products and the increasing awareness among researchers about the benefits of advanced therapies, driving the advanced therapy medicinal products (ATMP) CDMO market growth. Tissue engineering has greatly benefited in recent years from technological development. The damaged tissues and organ function are replaced or restored using this technique. Similarly, gene and cell therapy are attracting a lot of patients for the treatment of rare diseases, whose incidence is rising globally.

With rising demand for robust disease treatment therapies, key players have focused their efforts to ramp up research and development for effective gene therapies that target the cause of disorder at a genomic level. According to ASGCT, the number of cell and gene therapies in the U.S. pipeline programs (phase I-III trials) increased from 483 in 2021 to 529 in 2022. Furthermore, the FDA delivers constant support for innovations in the gene therapy field via a number of policies with regard to product manufacturing. In January 2020, the agency released six final guidelines on the manufacturing and clinical development of safe & efficient gene therapy products.

Moreover, awareness about ATMP treatment options is being driven by initiatives aimed at informing the public about the benefits of these products, which, in turn, is leading to increased adoption of advanced therapies and fueling market growth for CDMOs. For instance, Alliance for Regenerative Medicine Foundation for Cell and Gene Medicine prioritizes activities for increasing public awareness through educational programs, underlining the clinical & societal benefits of regenerative medicine.

Increasing clinical trial activity along with new product launches generates growth opportunities for the market. As of 2022, there are 1451 ATMPs in preclinical stages and 535 are being studied in Phase 1 to 3 studies. Since August 2020, EMA has approved six of these additional ATMPs, and five more will be approved by 2023. In the UK, there were approximately 168 advanced therapy medicinal product trials underway in 2021, up from the 154 studies reported the year before, which is a 9% increase. 2021 saw a 32% increase in phase 1 trials, indicating a significant shift from experimental medicines to first-in-human studies.

On the other hand, key players are undertaking various strategic initiatives to introduce novel products, which is expected to propel market growth. For instance, in March 2021, CureVac N.V. signed a partnership agreement with Celonic Group, engaged in the manufacture of CVnCoV, CureVacs mRNA-based COVID-19 vaccine candidate. CureVac's COVID-19 vaccine candidate is manufactured at Celonic's commercial manufacturing unit for ATMPs and biologics in Heidelberg, Germany. Under the terms of the commercial supply agreement, the Celonic facility could produce over 100 million doses of CVnCoV.

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Advanced Therapy Medicinal Products CDMO Market Trends

Segments Insights:

Product Insights

The gene therapy segment held the largest share of over 49.11% in 2023. Increase in financial support and rise in number of clinical trials for gene therapies are driving demand for gene therapy segment. In 2020, in the first three quarters, gene therapies attracted financing of over USD 12 billion globally, with around 370 clinical trials underway. Additionally, in mid-2022, approximately 2,000 gene therapies were in development, targeting several therapeutic areas, such as neurological, cancer, cardiovascular, blood, and infectious diseases.

The cell therapy segment is expected to show lucrative growth over the forecast period. The field of cellular therapeutics is constantly advancing with inclusion of new cell types, which, in turn, provides ample opportunities for companies to enhance their market positions. Furthermore, the market is attracting new entrants due to high unmet demand for cell therapy manufacturing, the recent approval of advanced therapies, and proven effectiveness of these products.

Indication Insights

The oncology segment accounted for the largest revenue share in 2023. The segments dominance is attributed to disease burden, strategic initiatives undertaken by key players, and availability of advanced therapies used for treating various cancer indications. In January 2021, around 18,000 to 19,000 patients and 124,000 patients were estimated to be potential patients for treating cancer using cell & gene therapy products Kymriah (Novartis AG) and Yescarta (Gilead Sciences, Inc.), respectively. Furthermore, a publication on PubMed reports that as of the conclusion of the first quarter of 2023, there have been over 100 distinct gene, cell, and RNA therapies approved globally, along with an additional 3,700-plus in various stages of clinical and preclinical development.

The cardiology segment is estimated to register the fastest CAGR over the forecast period. This is attributed to the increasing prevalence of cardiovascular diseases and research collaboration for development of advanced therapies. For instance, in October 2023, Cleveland Clinic administered a novel gene therapy to the first patient globally as part of a clinical trial, aiming to deliver a functional gene to combat the primary cause of hypertrophic cardiomyopathy (HCM). Similarly, in February 2021, Trizell GmbH entered into partnership with Catalent, Inc. for development of phase 1 cell therapy to treat micro- and macroangiopathy. Trizell's medication is an Advanced Therapy Medicinal Product (ATMP) that employs regulatory macrophagesa platform technology developed in Germany.

Phase Insights

The phase I segment dominated the market in 2023 due to growing R&D activities and increasing number of human trials for advanced therapies. Phase 1 helps ensure the safety levels of a drug at different doses and dosage forms administered to a small number of patients. This phase is mainly conducted to determine the highest dose a patient can take without any adverse effects. Around 70% of drugs in phase 1 move to the next phase.

The phase II segment has been anticipated to show lucrative growth over the forecast period. Phase II clinical studies comprise the largest number of developing ATMPs, due to the high clearance rate of phase I clinical studies. According to data published by Alliance for Regenerative Medicine, as of June 2022, more than 2,093 clinical trials are ongoing globally, out of which 1,117 are under phase II clinical trials accounting for 53%. Thus, the increase in number of products in phase II is driving the segment.

Regional Insights

North America dominated the overall market share of 49.11% in 2023. This can be attributed to increasing outsourcing activities and rising awareness about advanced therapy. North America has consistently been a leader in R&D for advanced treatments, and it is anticipated that it will keep this position during the forecast period. Recent approvals of products such as Kymriah and Yescarta have propelled investments in the regional market. Moreover, in March 2021, the U.S. FDA approved Abecma, the first approval of CAR-T cells to fight against cancer. Similarly, in December 2023, Casgevy and Lyfgenia, the initial cell-based gene therapies for sickle cell disease (SCD) in patients aged 12 and above, received approval from the U.S. Food and Drug Administration, marking a significant milestone.

The U.S. accounted for the largest share of the global market in the North America region in 2023. The U.S. maintains dominance in this sector due to the presence of a robust and highly advanced biopharmaceutical industry with a considerable focus on research and development. Additionally, the continuous presence of numerous pharmaceutical and biotechnology companies, along with academic and research institutions, generates a sustained demand for rigorous safety testing, further reinforcing the country's leadership in the field.

The Asia Pacific region is expected to grow at the fastest CAGR over the forecast period due to the increasing demand for novel ATMPs and rising R&D activities to develop novel therapies. Moreover, the market growth is driven by continuously expanding CDMO Cell Therapy in the country, a number of domestic players have collaborated with biotech companies from other countries involved in mesenchymal stem cell research and therapy development. In addition, in September 2022 Takara Bio, Inc. launched CDMO Cell Therapy for gene therapy products using siTCR technology for its genetically modified T-cell therapy products.

China accounted for the largest share of the global market in the Asia Pacific region in 2023 due to its strategic focus on advancing research and development capabilities, particularly in the pharmaceutical and biotechnology sectors. Additionally, with a rapidly growing biopharmaceutical industry and supportive government initiatives, China has become a key market for advanced therapy medicinal products (CDMO) market.

Recent Developments

Key Companies & Market Share Insights

Some of the key players operating in the market include AGC Biologics,WuXi Advanced Therapies and Celonic

Minaris Regenerative Medicine and BlueReg are some of the emerging market players in the global market.

Key Advanced Therapy Medicinal Products CDMO Companies:

Segments Covered in the Report

This report forecasts revenue growth at country levels and provides an analysis of the latest industry trends in each of the sub-segments from 2021 to 2033. For this study, Nova one advisor, Inc. has segmented the Advanced Therapy Medicinal Products CDMO market.

By Product

By Phase

By Indication

By Region

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Advanced Therapy Medicinal Products CDMO Industry is Rising Rapidly - BioSpace

Raiden Pham

Parents of children with rare diseases go to endless lengths to raise funds and awareness for research that might lead to a cure. Now, the story of 4-year-old Raiden Pham has been to the moon. He has an ultra-rare neurodegenerative disease known as UBA5 disorder that UMass Chan Medical School researchers are targeting.

The story of Raidens journey and its message of love, hope and strength is included on an indestructible digital time capsule of art, music, film and history, as part of the Lunaprise Moon Museum Mission, which was onboard the Odysseus spacecraft that landed on the moon Feb. 22.

When we think about gene therapy, or any kind of cure or treatment for these rare diseases, its always considered a moonshot, but thats not the case anymore in todays world, said Tommy Pham, Raidens father. Were willing to do whatever it takes to save my son and kids with UBA5 disorder and hopefully inspire the next generation of rare disease parents to go on this fight and have hope.

Since 2021, the Raiden Science Foundation, founded by Tommy and Linda Pham, of Beaverton, Oregon, on behalf of their son, has raised around $1 million of its $4 million goal, which supports research in UMass Chans Translational Institute for Molecular Therapeutics and other partner institutions.

The research on UBA5 is led by Toloo Taghian, PhD, instructor in radiology in the lab of Heather Gray-Edwards, DVM, PhD, assistant professor of radiology in the Horae Gene Therapy Center.

Dr. Taghian has identified the top two viral vector constructs for UBA5 expression in-vivo, which show great promise in successfully delivering UBA5 gene therapy to the targeted cells. Taghian and her team are now testing their efficacy in correcting the protein malfunction and treating the underlying cause of this disease and will soon initiate toxicology studies to assess their safety.

Working with Raiden Science Foundation to develop a gene therapy for UBA5 has been an impactful journey, said Taghian. The dedication of the Pham family in supporting UBA5 research allows the UMass Chan team to work toward unpacking the basic science underlying this ultra-rare disease in parallel with our gene therapy development program.

How Raidens story got to the moon was a journey of persistent efforts to raise awareness and support by the Phams. In October 2022, Raiden Science Foundation held a gaming charity stream, Kombat4Rare, based on the Mortal Kombat franchise. One of the main characters in Mortal Kombat is Raiden, named after the God of Thunder in Japanese mythology.

The response from the gaming and entertainment community was enthusiastic, and a few months later Tommy Pham was invited to be featured at a charity event in Marina del Rey, California. Dallas Santana, founder of Space Blue, the exclusive curator of the Lunaprise Museum, was touched by Tommys message and told him Raidens story should be included on the Lunaprise Moon Museum to inspire people on Earth.

Noting that it has been more than 50 years since the last American space capsule landed on the moon, Tommy said, We dont have to wait another 50 years for gene therapy. It could be done now in the coming years. We need to figure out a way with all the right stakeholders to unlock gene therapy for so many other kids suffering different rare diseases, not just us.

Donations to support UBA5 gene therapy at UMass Chan can be made here.

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Story of boy with ultra-rare UBA5 disorder being studied at UMass Chan goes to the moon - UMass Medical School

Human Avatars Help Make Gene Therapy More Effective  Duke University School of Medicine

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Human Avatars Help Make Gene Therapy More Effective - Duke University School of Medicine

US Retinal Specialists Highlight the Greatest Opportunity for Gene Therapies  Yahoo Finance

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US Retinal Specialists Highlight the Greatest Opportunity for Gene Therapies - Yahoo Finance

Gene therapy for pain treatment  Drug Discovery News

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Gene therapy for pain treatment - Drug Discovery News

Macular Degeneration Research Heads to the ISS  ISS National Lab

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Macular Degeneration Research Heads to the ISS - ISS National Lab