MHRA approves Madrigal’s resmetirom (Rezdiffra) as the first UK treatment for metabolic dysfunction‑associated steatohepatitis (MASH) with stage 2–3 fibrosis, expanding options for patients at high risk of progression.
Written By: Nikita Jha, BPharm
Reviewed By: Pharmacally Editorial Team
The Medicines and Healthcare products Regulatory Agency (MHRA) has approved resmetirom (Rezdiffra) for adults with metabolic dysfunction-associated steatohepatitis (MASH) and stage 2 or stage 3 liver fibrosis. The authorization, granted to Madrigal Pharmaceuticals EU Limited through the International Recognition Procedure (IRP), covers 60 mg, 80 mg, and 100 mg film-coated tablets.
The decision makes resmetirom the first approved medicine in the UK for patients with MASH and moderate to advanced liver fibrosis.
Disease Burden and Unmet Need
MASH is the progressive inflammatory form of nonalcoholic fatty liver disease (NAFLD) and a leading cause of chronic liver disease worldwide. The condition develops when excess fat accumulates in the liver and triggers inflammation and cellular injury. Over time, this can progress to fibrosis, cirrhosis, liver failure, hepatocellular carcinoma, and increased liver-related mortality. Patients with moderate to advanced fibrosis face the highest risk of disease progression and complications. Until now, no pharmacologic therapies were approved in the UK for this patient population.
Pivotal Clinical Evidence
The MHRA based its decision on a pivotal 12-month study involving 917 adults with MASH and stage 2–3 liver fibrosis who received either resmetirom or placebo.
Depending on the dose administered, 26% to 30% of patients receiving resmetirom achieved MASH resolution without worsening fibrosis, compared with 10% of patients receiving placebo. In addition, 27% to 29% of treated patients experienced improvement in liver fibrosis without worsening MASH, versus 17% in the placebo group.
These results demonstrated clinically meaningful improvements across key histologic markers associated with long-term liver outcomes and disease progression.
Safety Profile
Resmetirom was generally well tolerated. The most common adverse events were diarrhea and nausea, each occurring in more than 10% of patients. The overall safety profile was consistent with previous studies, and no new safety concerns were identified during regulatory review.
Mechanism of Action
Resmetirom is an oral, liver-directed thyroid hormone receptor beta (THR-β) agonist. In patients with MASH, reduced THR-β activity within hepatocytes impairs fat metabolism and contributes to disease progression. By selectively activating THR-β, resmetirom increases hepatic fat breakdown, reduces liver fat accumulation, and addresses key drivers of inflammation and fibrosis. Its liver-targeted activity helps limit systemic thyroid hormone effects while supporting a favorable safety profile.
Regulatory and Global Context
Commenting on the approval, Julian Beach, Executive Director of Healthcare Quality and Access at the MHRA, said the authorization provides the first treatment option for patients with MASH and moderate to advanced fibrosis while reflecting the agency’s commitment to maintaining rigorous regulatory standards and enabling timely access to innovative medicines.
The UK authorization follows the U.S. FDA approval of resmetirom in March 2024, highlighting growing regulatory recognition of the therapy’s clinical benefit. As healthcare systems confront the rising burden of metabolic liver disease, resmetirom is poised to become an important treatment option for patients with progressive MASH and clinically significant fibrosis.
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About the Writer
Nikita Jha, BPharm (LinkedIn) a pharmacy graduate specializing in medical writing, with a strong ability to interpret complex medical and regulatory information and translate it into clear, accurate, and evidence-based healthcare content. Known for her attention to detail and precision, she focuses on delivering high-quality scientific communication that supports drug safety and informed decision-making.