‘Monumental occasion’: FDA approves Madrigal’s Rezdiffra as first treatment for MASH
Click Here to Manage Email Alerts
Madrigal Pharmaceutical’s Rezdiffra received accelerated FDA approval for the treatment of patients with metabolic dysfunction-associated steatohepatitis with moderate-to-advanced fibrosis, according to a company release.
Rezdiffra (resmetirom), an oral thyroid hormone receptor-beta selective agonist is the first FDA- approved treatment for MASH, formerly NASH. In May 2023, an FDA advisory committee struck down the lead contender for MASH treatment, obeticholic acid (Ocaliva, Intercept Pharmaceuticals), citing a “concerning” benefit-risk profile.
“The approval of resmetirom to treat patients with moderate-to-advanced fibrosis is a monumental occasion that will have tremendous implications for the field and for our patients suffering from this progressive liver disease,” Stephen A. Harrison, MD, FAASLD, founder of Pinnacle Clinical Research and Summit Clinical Research and visiting professor of hepatology at the University of Oxford, told Healio. “I’m hopeful that the approval of this medication will not only bring more broad-based awareness of this disease to the community and to the clinicians who treat these patients but will also allow us to halt or reverse the disease in a number of our patients that are treated.”
The agency based its decision on data from the ongoing pivotal, multicenter, randomized, double-blind, placebo-controlled phase 3 MAESTRO-NASH trial, in which 1,759 patients with biopsy-confirmed MASH either received once-daily Rezdiffra (80 mg or 100mg) or placebo.
Compared with placebo, after 52 weeks of treatment, both 100 mg and 80 mg doses of Rezdiffra achieved statistically significant improvement on the study’s two primary endpoints: NASH resolution with no worsening of fibrosis, and an improvement in fibrosis by at least one stage with no worsening of the NAFLD activity score, the release stated.
According to the company, those enrolled in the trial for the initial 52-week treatment period will continue for up to 54 months to measure hepatic clinical outcomes such as progression to cirrhosis on biopsy, hepatic decompensation events and all-cause mortality. This portion of the trial “is designed to generate confirmatory data that, if positive, will help verify Rezdiffra’s clinical benefit and may support full approval.”
“Madrigal would like to thank the many patients who made the accelerated approval of Rezdiffra possible by participating in our clinical studies,” Becky Taub, MD, founder, CEO and president of research & development at Madrigal, said in the release. “We believe Rezdiffra will change the treatment paradigm for NASH with moderate to advanced liver fibrosis, giving physicians a liver-directed therapy to help improve fibrosis and resolve NASH before their patients progress to cirrhosis.”
A liver biopsy to confirm diagnosis will not be required to prescribe Rezdiffra, the release noted, and the recommended dosage will be based on an individual’s actual body weight. For those who weigh less than 100 kg, the recommended dose is once-daily 80 mg while 100 mg is recommended for those who weigh 100 kg or more.
Common adverse events associated with Rezdiffra include nausea, pruritis, abdominal pain, vomiting, constipation and dizziness, as well as the possibility of serious side effects such as hepatotoxicity and gallbladder issues. The drug should not be used in patients with decompensated cirrhosis, the company warned.
Disclosures: Harrison reports financial relationships with 89 Bio, AgomAB, Akero Therapeutics, Alentis Therapeutics, Aligos Therapeutics, Alimentiv, Altimmune, Arrowhead Pharmaceuticals, Axcella Health, B Riley FBR, Bluejay Therapeutics, Boston Pharmaceuticals, Boxer Capital, Bristol Myers Squibb, BVF Partners, Canfite Biopharma, Chronwell, Cirius Therapeutics, CiVi Biopharma, Cohbar, Corcept Therapeutics, CymaBay Therapeutics, Echosens North America, Enyo Pharma, Fibronostics, Foresite Labs, Fortress Biotech, Galectin Therapeutics, Galecto, Galmed Pharmaceuticals, Genfit, Gilead Sciences, GSK, GNS Healthcare, Hepagene Therapeutics, Hepion Pharmaceuticals, Hepta Bio, Hightide Therapeutics, HistoIndex, Humana, Indalo Therapeutics, Inipharm, Intercept Pharmaceuticals, Ionis Pharmaceuticals, Kowa Research Institute, Liminal Biosciences, Madrigal Pharmaceuticals, Medpace, Merck, Metacrine, Metrea Biosciences, Microba, Molecular Genetics & Genomic Medicine, Neurobo Pharmaceuticals, NGM Biopharmaceuticals, Northsea Therapeutics, Novartis, Novo Nordisk, Nutrasource, Oppenheimer & Co., PathAI, Pfizer, Piper Sandler, Poxel, Ridgeline Therapeutics, Sagimet Biosciences, Sonic Incytes, Terns, Theratechnologies, Viking Therapeutics and Zafgen.
Click Here to Manage Email Alerts