Madrigal Pharmaceuticals, Inc.

The FDA said Wednesday it has okayed a non-invasive biomarker as an alternative to liver biopsy for assessing disease progression and treatment response in clinical trials of metabolic dysfunction-associated steatohepatitis (MASH) therapies.The agency’s Center for Drug Evaluation and Research (CDER) accepted a letter of intent to qualify liver stiffness measurement by vibration-controlled transient elastography as a surrogate endpoint for studies in patients with non-cirrhotic MASH having moderate-to-advanced fibrosis.“This proposal represents an important step toward adopting non-invasive tests in drug development for MASH," said Frank Anania, director of the division of hepatology and nutrition at CDER.As per the letter of intent, the proposed biomarker can potentially predict the risk of all-cause mortality or liver-related events in patients with MASH; the elastography-based measurements correlate with fibrosis severity — thereby offering a safer, more accessible way to monitor disease progression. Additionally, elimination of liver biopsies could ease patient recruitment, ensure broader representation, improve trial power, and speed up drug development.The FDA’s acceptance kicks off the Drug Development Tool qualification process, where developers can collaborate with the regulator to establish comprehensive validation requirements.Madrigal’s Rezdiffra (resmetirom) and Novo Nordisk’s Wegovy (semaglutide) remain the two approved MASH therapies in the US, with a bunch of other candidates, including GLP-1, FGF21, PPAR and THR-β agonists under investigation. For more, read: Vital Signs: Tracking the MASH queue for GLP-1 agonists.

SOUTH SAN FRANCISCO, Calif., Aug. 20, 2025 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced the appointment of James M. Daly to its Board of Directors effective August 19, 2025. Mr. Daly brings over 30 years of global biopharmaceutical leadership experience with particular expertise in commercialization to the Company’s Board of Directors. “Jim has longstanding expertise leading commercial launches of innovative therapies, coupled with extensive Board experience guiding later-stage, global biopharma companies,” said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. “We are pleased to welcome him to our Board and look forward to his contributions and oversight as our company advances toward becoming a fully integrated commercial organization.” Most recently, Mr. Daly served as the Chief Commercial Officer at Incyte Corporation where he led the launch of Jakafi® (ruxolitinib) and oversaw development of the company’s global commercial capabilities. Previously, he spent 10 years at Amgen where he held multiple senior leadership positions, including Senior Vice President of North America Commercial Operations, and launched several successful medicines including Neulasta®, Xgeva®, Nplate® and Vectibix®. He began his career at GlaxoSmithKline, serving in escalating positions of seniority over his 16-year tenure with the company. He earned a B.S. in Pharmacy and an M.B.A. from the University at Buffalo, SUNY. Mr. Daly currently serves on the Boards of Madrigal Pharmaceuticals, argenx SE, and Acadia Pharmaceuticals. About Cytokinetics Cytokinetics is a specialty cardiovascular biopharmaceutical company, building on its over 25 years of pioneering scientific innovations in muscle biology to advance a pipeline of potential new medicines for patients suffering from diseases of cardiac muscle dysfunction. Cytokinetics is readying for potential regulatory approvals and commercialization of aficamten, a cardiac myosin inhibitor following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in patients with obstructive hypertrophic cardiomyopathy (HCM). Aficamten is also being evaluated in additional clinical trials enrolling patients with obstructive and non-obstructive HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac myosin activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), ulacamten, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten, for the potential treatment of heart failure with preserved ejection fraction (HFpEF) and CK-089, a fast skeletal muscle troponin activator with potential therapeutic application to a specific type of muscular dystrophy and other conditions of impaired skeletal muscle function. For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube. Forward-Looking Statements This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements and claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements relating to Cytokinetics’ and its partners’ research and development activities of Cytokinetics’ product candidates. Such statements are based on management’s current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to the risks related to Cytokinetics’ business outlines in Cytokinetics’ filings with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and Cytokinetics’ actual results of operations, financial condition and liquidity, and the development of the industry in which it operates, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that Cytokinetics makes in this press release speak only as of the date of this press release. Cytokinetics assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. CYTOKINETICS® and the CYTOKINETICS and C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact:Cytokinetics Diane WeiserSenior Vice President, Corporate Affairs(415) 290-7757

CONSHOHOCKEN, PA, USA I August 19, 2025 I Madrigal Pharmaceuticals, Inc. (NASDAQ: MDGL), a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), today announced that the European Commission (EC) has granted conditional marketing authorization for Rezdiffra (resmetirom) for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. Rezdiffra is now the first and only approved therapy in the European Union (EU) for the treatment of MASH. Bill Sibold, Chief Executive Officer of Madrigal, stated, “This approval of Rezdiffra marks a historic breakthrough for patients in Europe living with MASH, a serious and progressive liver disease. MASH is the fastest-growing indication for liver transplantation in Europe, but until now, had no approved treatment. The European labelling for Rezdiffra will set an important precedent for the entire field, with no biopsy required to qualify for treatment with Rezdiffra and a clear focus on a distinct MASH patient population with high unmet need: those with moderate to advanced fibrosis (F2-F3). These patients require liver-directed treatment because they have a 10 to 17 times higher risk of liver-related mortality and are just one or two steps away from progressing to cirrhosis.” MASH is a leading cause of liver-related mortality and an increasing burden on healthcare systems globally. Madrigal estimates that approximately 370,000 patients with MASH with moderate to advanced fibrosis are currently diagnosed and under the care of a liver specialist across Europe. Rezdiffra is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. The EC Decision was based on Rezdiffra’s favorable benefit-risk profile – including the positive results from the pivotal Phase 3 MAESTRO-NASH trial , which achieved both fibrosis reduction and MASH resolution primary endpoints. Rezdiffra also reduced liver stiffness, liver fat, liver enzymes, and atherogenic lipids in the MAESTRO-NASH trial, and improved health-related quality of life. At one year, 91% of patients treated with Rezdiffra 100 mg achieved improvement or stabilization of liver stiffness as measured by vibrational-controlled transient elastography (VCTE), a test that is frequently used to monitor treatment response in clinical practice. Frank Tacke, MD, PhD, MBHA, Chairman of Hepatology & Gastroenterology at the Charité – Universitätsmedizin Berlin, Germany, stated, “The approval of Rezdiffra is a transformational moment for the European MASH community and I’m looking forward to offering this important new treatment option to my patients with moderate to advanced fibrosis. Rezdiffra is included in the European MASH treatment guidelines and hundreds of patients participated in the Phase 3 studies, so there is already sound clinical experience with Rezdiffra in Europe.” This approval follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) adopted in June 2025. The EC Decision is valid in all 27 Member States of the EU, as well as in Iceland, Liechtenstein and Norway. The timing for access to Rezdiffra in individual countries will depend on multiple factors, including the completion of reimbursement procedures. Madrigal expects to launch Rezdiffra in Europe on a country-by-country basis commencing with Germany in the fourth quarter of 2025. About MASH Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), is a serious liver disease that can progress to cirrhosis, liver failure, liver cancer, need for liver transplantation, and premature mortality. MASH is the leading cause of liver transplantation in women and the second leading cause of all liver transplantation in the U.S., and the fastest-growing indication for liver transplantation in Europe. Once patients progress to MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis), the risk of adverse liver outcomes increases dramatically: these patients have a 10-17 times higher risk of liver-related mortality as compared to patients without fibrosis. Those who progress to cirrhosis face a 42 times higher risk of liver-related mortality, underscoring the need to treat MASH before complications of cirrhosis develop. MASH is also an independent driver of cardiovascular disease, the leading cause of mortality for patients. As MASH disease awareness improves and disease prevalence increases, the number of diagnosed patients with MASH with moderate to advanced fibrosis or compensated MASH cirrhosis (F2-F4c) is expected to grow. About Rezdiffra Rezdiffra is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. It is the first approved medication for the treatment of MASH in the US and EU. Rezdiffra received accelerated approved from the U.S. Food and Drug Administration (FDA) in March 2024. In the U.S., it is indicated in conjunction with diet and exercise for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). This indication is approved under accelerated approval based on improvement of MASH and fibrosis. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Rezdiffra received conditional marketing authorization from the European Commission (EC) in August 2025. A conditional marketing authorization is granted to a medicinal product that fulfils an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. Rezdiffra is not approved in any geography for the treatment of patients with cirrhosis. The ongoing, fully enrolled MAESTRO-NASH OUTCOMES trial is evaluating progression to liver decompensation events in patients with compensated MASH cirrhosis treated with Rezdiffra versus placebo. About Madrigal Madrigal Pharmaceuticals, Inc. (Nasdaq: MDGL) is a biopharmaceutical company focused on delivering novel therapeutics for metabolic dysfunction-associated steatohepatitis (MASH), a liver disease with high unmet medical need. Madrigal’s medication, Rezdiffra (resmetirom), is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of MASH. Rezdiffra is the first and only medication approved by both the FDA and European Commission for the treatment of MASH with moderate to advanced fibrosis (F2 to F3). An ongoing Phase 3 outcomes trial is evaluating Rezdiffra for the treatment of compensated MASH cirrhosis (F4c). For more information, visit www.madrigalpharma.com . SOURCE: Madrigal Pharmaceuticals