Astellas and Seagen Announce Positive Topline Results from Second Cohort of Patients in Phase 2 Pivotal Trial of PADCEV (enfortumab vedotin-ejfv) in…
Posted: October 13, 2020 at 11:57 am
TOKYO and BOTHELL, Wash., Oct. 12, 2020 /PRNewswire/ --Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") and Seagen Inc. (Nasdaq: SGEN) today announced positive topline results from the second cohort of patients in the pivotal phase 2 single-arm clinical trial known as EV-201. The cohort is evaluating the antibody-drug conjugate PADCEV (enfortumab vedotin-ejfv) for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1/L1 inhibitor and have not received a platinum-containing chemotherapy and are ineligible for cisplatin. Results showed a 52 percent objective response rate (ORR) [95% Confidence Interval (CI): 40.8, 62.4] per blinded independent central review and a median duration of response of 10.9 months. The most frequently reported treatment-related adverse events Grade 3 or greater that occurred in more than 5 percent of patients were: neutropenia, rash, fatigue, increased lipase, diarrhea, decreased appetite, anemia and hyperglycemia. Data from cohort 2 of the trial will be submitted for presentation at an upcoming scientific congress and will be discussed with regulatory authorities.
PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.1,2 The U.S. Food and Drug Administration (FDA) granted accelerated approval to PADCEV in 2019 based on results from the first cohort in this trial, which included patients whose disease hadprogressed during or following platinum-based chemotherapy and a PD-1/L1 inhibitor.
"Advanced urothelial cancer in patients who have received immunotherapy and are ineligible for cisplatin is a particularly difficult disease to treat," said Arjun Balar, M.D., Associate Professor of Medicine, Director Genitourinary Medical Oncology Program, NYU Laura and Isaac Perlmutter Cancer Center, NYU Langone Health and an investigator for the trial. "Typically, these patients are frail, suffer from multiple comorbidities beyond their urothelial cancer and are not able to tolerate additional treatment beyond immunotherapy, leading many to discontinue therapy altogether."
"We are committed to developing new treatments for patients with hard-to-treat cancers, such as those with locally advanced or metastatic urothelial cancer that has progressed following treatment with a PD-1 or PD-L1 inhibitor and who are ineligible for cisplatin therapy," said Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas. "We look forward to discussing these data with regulatory authorities including the FDA."
"This is the first trial to report objective responses in patients with advanced urothelial cancer who had previously received immunotherapy but were ineligible for cisplatin in this setting due to inadequate kidney function or other conditions," said Roger Dansey, M.D., Chief Medical Officer at Seagen. "These promising new data from EV-201 may support a regulatory application to extend use of PADCEV in U.S. patients whose cancer has progressed after immunotherapy and who are ineligible for cisplatin."
Urothelial cancer is the most common type of bladder cancer (90 percent of cases), and can also be found in the urothelial cells that line the renal pelvis (where urine collects inside the kidney), ureter (tube that connects the kidneys to the bladder) and urethra.3 Globally, approximately 580,000 people will be diagnosed with bladder cancer in 2020, and bladder cancer will be attributed to approximately 210,000 deaths worldwide.4
About the EV-201 TrialThe EV-201 trial (NCT03219333) is a single-arm, pivotal phase 2 clinical trial of enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who have been previously treated with a PD-1 or PD-L1 inhibitor, including those who have also been treated with a platinum-containing chemotherapy (cohort 1) and those who have not received a platinum-containing chemotherapy in this setting and who are ineligible for cisplatin (cohort 2). The trial enrolled 128 patients in cohort 1 and 91 patients in cohort 2 at multiple centers internationally.5 The primary endpoint is confirmed objective response rate per blinded independent central review. Secondary endpoints include assessments of duration of response, disease control rate, progression-free survival, overall survival, safety and tolerability.
For more information about the EV-201 clinical trial, please visit clinicaltrials.gov.
About PADCEV (enfortumab vedotin-ejfv)PADCEV was approved by the U.S. Food and Drug Administration (FDA) in December 2019 and is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting. PADCEV was approved under the FDA's Accelerated Approval Program based on tumor response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.1
PADCEV is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer.1,2 Nonclinical data suggest the anticancer activity of PADCEV is due to its binding to Nectin-4 expressing cells followed by the internalization and release of the anti-tumor agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).2 PADCEV is co-developed by Astellas and Seagen.
PADCEV Important Safety Information
Warnings and Precautions
Adverse ReactionsSerious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, and sepsis (each 0.8%).
Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%). Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).
The most common adverse reactions (20%) were fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%). The most common Grade 3 adverse reactions (5%) were rash (13%), diarrhea (6%) and fatigue (6%).
Lab AbnormalitiesIn one clinical trial, Grade 3-4 laboratory abnormalities reported in 5% were: lymphocytes decreased (10%), hemoglobin decreased (10%), phosphate decreased (10%), lipase increased (9%), sodium decreased (8%), glucose increased (8%), urate increased (7%), neutrophils decreased (5%).
Drug Interactions
Specific Populations
For more information, please see the full Prescribing Information for PADCEV here.
About Astellas Astellas Pharma Inc. is a pharmaceutical company conducting business in more than 70 countries around the world. We are promoting the Focus Area Approach that is designed to identify opportunities for the continuous creation of new drugs to address diseases with high unmet medical needs by focusing on Biology and Modality. Furthermore, we are also looking beyond our foundational Rx focus to create Rx+ healthcare solutions that combine our expertise and knowledge with cutting-edge technology in different fields of external partners. Through these efforts, Astellas stands on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website athttps://www.astellas.com/en.
About Seagen Seagen Inc. is a global biotechnology company that discovers, develops and commercializes transformative cancer medicines to make a meaningful difference in people's lives. Seagen is headquartered in the Seattle, Washington area, and has locations in California, Canada, Switzerland and the European Union. For more information on our marketed products and robust pipeline, visit http://www.seagen.com and follow @SeagenGlobal on Twitter.
About the Astellas and Seagen CollaborationAstellas and Seagen are co-developing PADCEV (enfortumab vedotin-ejfv) under a collaboration that was entered into in 2007 and expanded in 2009.
Astellas Cautionary NotesIn this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management's current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas' intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development), which is included in this press release is not intended to constitute an advertisement or medical advice.
Seagen Forward Looking StatementsCertain statements made in this press release are forward looking, such as those, among others, relating to the submission of data from cohort 2 of the EV-201 trial for presentation at an upcoming scientific congress; intended regulatory actions, including the potential submission of a regulatory application to extend the use of PADCEV in U.S. patients or plans to discuss data from cohort 2 of the EV-201 trial with regulatory authorities; and the therapeutic potential of PADCEV, including its efficacy, safety and therapeutic uses. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include that the data from cohort 2 of the EV-201 trial may not be selected for presentation at scientific congresses; the possibility of delays in the submission of any regulatory application to extend the use of PADCEV in U.S. patients; that the results from cohort 2 of the EV-201 trial may not be enough to support any approvals by regulatory authorities; that any product labeling that is approved may be narrower or less desirable than anticipated; the risk of adverse events or safety signals; and the possibility that adverse regulatory actions may occur. More information about the risks and uncertainties faced by Seagen is contained under the caption "Risk Factors" included in the company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2020 filed with the Securities and Exchange Commission. Seagen disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.
1PADCEV [package insert]. Northbrook, IL: Astellas, Inc.
2Challita-Eid P, Satpayev D, Yang P, et al. Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models. Cancer Res 2016;76(10):3003-13.
3American Society of Clinical Oncology. Bladder cancer: introduction (10-2017). https://www.cancer.net/cancertypes/bladder-cancer/introduction. Accessed 05-09-2019.
4International Agency for Research on Cancer. Cancer Tomorrow: Bladder. http://gco.iarc.fr/tomorrow. Accessed 07-31-2020.
5ClinicalTrials.gov Identifier: NCT03219333. A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer (EV-201). https://clinicaltrials.gov/ct2/show/NCT03219333. Accessed on 08-03-2020.
SOURCE Astellas Pharma Inc.
- A dive into the genetic history of India, and the role of vitamin A in skin repair - Science - March 12th, 2024
- Vitamin A could have a key role in both stem cell biology and wound healing: Study - Medical Dialogues - March 12th, 2024
- Fiona M. Watt receives the 2024 ISSCR Achievement Award for her seminal work with skin stem cells - EurekAlert - February 13th, 2024
- Eggs from men, sperm from women: Stem cell therapy may just turn reproduction upside down! - The Economic Times - January 20th, 2024
- Herbosa: Clinic under probe after skin treatments linked to womans death - Philstar.com - January 20th, 2024
- These Will Be the Biggest Skin-Care Trends of 2024 - Allure - December 25th, 2023
- Defence Mechanisms: Four ways your body is protecting you every time you fall sick - indulgexpress - May 13th, 2023
- Treat Yourself to a Spa Day With a $100 Deal on $600 Worth of Products From Elemis, 111SKIN, Nest & More - E! NEWS - May 13th, 2023
- Cell-Based Regenerative Medicine Market Size to Witness Rapid Growth at a CAGR of 15% by 2032 | insightSLICE - EIN News - May 5th, 2023
- Best EGF Serum (Epidermal Growth Factor Serum) In 2023: Discover the Ultimate In Skin Rejuvenation - Outlook India - April 18th, 2023
- 7-year-old vows to find a cure for brother in need of bone marrow transplant - WJLA - February 26th, 2023
- 10th Annual Regenerative Medicine Essentials Course and World Stem Cell Summit Return to Live with Virtual Option in 2023 - Newswise - February 10th, 2023
- Leukaemia signs and symptoms: How to detect, treat the aggressive blood cancer - Hindustan Times - February 10th, 2023
- Adult stem cell - Wikipedia - December 28th, 2022
- Stem cells: a brief history and outlook - Science in the News - December 28th, 2022
- What are totipotent stem cells & what can they do? - The Niche - December 28th, 2022
- Certain Foods Discovered to Increase Stem Cells, Cell Regeneration - December 28th, 2022
- Skin Cell - The Definitive Guide | Biology Dictionary - December 28th, 2022
- Women are using menstrual blood for skincare here's why I think beauty has gone too far this time - VOGUE India - December 4th, 2022
- Mesenchymal Stem Cells | Properties, Process, Functions, & Therapies - November 26th, 2022
- Childbirth - Wikipedia - November 26th, 2022
- Unlocking the Mysteries of Brain Regeneration Groundbreaking Study Offers New Insight - SciTechDaily - September 30th, 2022
- TikTok Made Me Buy It: The Creamy Concealer That Instantly Veils Dark Circles and Hyperpigmentation - Vogue - September 30th, 2022
- Here Is Why You Heal Slower As You Age - Health Digest - September 30th, 2022
- A glimpse into Indian consumers expectations for cosmetic treatments and consumption insights - The Financial Express - September 30th, 2022
- Propanc Biopharma Targets Pancreatic & Ovarian Cancers for PRP Clinical Studies with Combined Markets to Reach Over $14.3 Billion by 2027 -... - September 30th, 2022
- Hair-bearing human skin generated entirely from pluripotent stem cells - September 13th, 2022
- FACTORFIVE Skincare The Power of Stem Cells for Skin - September 13th, 2022
- Stem cells: Sources, types, and uses - Medical News Today - September 13th, 2022
- Hematopoietic Stem Cells | Hematopoiesis | Properties & Functions - September 13th, 2022
- Top 3 grants in regenerative medicine: July 2022 - RegMedNet - September 13th, 2022
- Beauty maybe be skin deep, but AI finds revenue on the faces surface - Biometric Update - September 13th, 2022
- September is Blood Cancer Awareness Month: All You Need to Know - News18 - September 13th, 2022
- 10 Facts That Prove Memory Is Not What You Think - Listverse - September 13th, 2022
- Seagen, Astellas and Merck Announce Results of Clinical Trial Investigating PADCEV (enfortumab vedotin-ejfv) with KEYTRUDA (pembrolizumab) and PADCEV... - September 13th, 2022
- NYC Dermatologist, Dr. Julie Russak, launches first Anti-Aging Wellness Program of its kind in the U.S. - PR Web - September 13th, 2022
- Curbing COVID-Related Hair Loss: Russak Dermatology's Hair Restoration Therapy - PR Web - August 11th, 2022
- Jennifer Aniston And Sandra Oh Swear By This Moisturizer That Shoppers Say Created Permanent Changes To Their Skin - Suggest - August 11th, 2022
- Victoria Beckham and Kim Kardashian are fans of Augustinus Baders skincare range - and you can get 20% off - The Mirror - August 11th, 2022
- How your intestines repair and renew themselves - Futurity: Research News - August 3rd, 2022
- Bone marrow imaging reveals the migration dynamics of neonatal hematopoietic stem cells | Communications Biology - Nature.com - August 3rd, 2022
- Global Stem Cells Group Expands Its Stem Cell Therapy and Regenerative Medicine Centers to Indonesia - GlobeNewswire - August 3rd, 2022
- NuFace Is Having a Major Sale During Amazon Prime Day 2022 See Deals on Trinity, NuBody, and More - Allure - July 17th, 2022
- Global Stem Cell Manufacturing Market Value Projected To Reach USD 21.71 Billion By 2029, Registering A CAGR Of 9.1% - Digital Journal - July 17th, 2022
- The 'Benjamin Button' effect: Scientists can reverse aging in mice. The goal is to do the same for humans - KITV Honolulu - July 17th, 2022
- Why do some women struggle to breastfeed? A UCSC researcher on what we know, and don't - Lookout Santa Cruz - July 17th, 2022
- What if we could genetically dial back our skin? - The Week - June 28th, 2022
- Reviewers Are Calling This Hydrating Stem Cell Cream Miraculous - Us Weekly - June 28th, 2022
- UVR Promotes Keratinocyte Phagocytosis and Skin Pigmentation Through T | CCID - Dove Medical Press - June 28th, 2022
- 'A new Alzheimer's treatment is on the horizon': Cell therapy reverses dementia-like syndrome in dogs - BioPharma-Reporter.com - June 28th, 2022
- What Is Vegan Collagen? And the 6 Best Products to Try - VegNews - June 28th, 2022
- Shock Wave Uses and Benefits The Horse - TheHorse.com - June 28th, 2022
- Chao Discusses Stratifying and Treating Patients With Graft-Vs-Host Disease - Targeted Oncology - June 28th, 2022
- Elucidating the developmental origin of life-sustaining adrenal glands | Penn Today - Penn Today - May 24th, 2022
- All Things Hot In The Beauty Space In The Month Of May | Femina.in - Femina - May 24th, 2022
- Anti-Aging Products and Therapies Market Size Estimated to Reach $93.2 Billion by 2027 - Digital Journal - April 2nd, 2022
- Learning from the single cell: A new technique to unravel gene regulation - EurekAlert - April 2nd, 2022
- Sailing the Genome in Search of Safe Harbors - Technology Networks - April 2nd, 2022
- 7 Easy Ways to Transition Your Skin Care Routine for Spring - Vancouver Magazine - April 2nd, 2022
- INTERNATIONAL STEM CELL CORP MANAGEMENT'S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS (form 10-K) - Marketscreener.com - April 2nd, 2022
- Syrian refugee is thriving five years after last-gasp gene therapy - STAT - STAT - December 9th, 2021
- Benefits of Pulsed Laser-based Skin Therapy - Newswise - December 9th, 2021
- Mesoblast has long been the one poster child for stem cell therapy. Now Cynata and other ASX stocks have e ... - Stockhead - December 9th, 2021
- In This Issue - pnas.org - December 9th, 2021
- UNM research team finds lungfish cocoon is living tissue with antimicrobial functions - UNM Newsroom - December 9th, 2021
- Mini-brain model of frontotemporal dementia demonstrates the stages of dysfunction that lead to cell death - National Institute on Aging - November 7th, 2021
- A major research project to advance regenerative therapy for epidermolysis bullosa (EB) using transgenic stem cells - PR Web - November 7th, 2021
- 15 Best Peptide Skin-Care Products 2021 for Smoother, Firmer, and Plumper Skin - Allure - November 7th, 2021
- Lab-Growing Everything Might Be The Only Way To Attain A Sustainable World - Intelligent Living - November 7th, 2021
- Common But Overlooked Causes for Hair Loss - The Cherokee Scout - November 7th, 2021
- How To Look Less Tired According To Experts | Grazia - Grazia - November 7th, 2021
- Losing Your Hair? You Might Blame the Great Stem Cell Escape. - The New York Times - October 5th, 2021
- Stem cells may be the key to saving white rhinos from extinction - Sciworthy - October 5th, 2021
- The Best Skincare Treatments For Time-Crunched Moms (Or Anyone Else Who Only Has Five Minutes To Spare) - Forbes - October 5th, 2021
- Stanford neuroscientist's 'assembloids' pave the way for innovative brain research - Scope - October 5th, 2021
- 3 of the Best Fall Beauty Buys - Pursuitist - October 5th, 2021
- Can Obesity Lead to Hair Fall? Here's What The Research Says - India.com - October 5th, 2021
- 12 of the best face serums 2021 - Medical News Today - October 5th, 2021
- The Number 1 Serum in the U.S. Is on Sale at SaksAlong With Other Never-Discounted Buys - Well+Good - October 5th, 2021
- Man discovers nasty red rash on his hands and elbows is potentially fatal - The Mirror - October 5th, 2021