FULL APPROVAL

Madrigal's Rezdiffra won full FDA approval for MASH with fibrosis

The accelerated approval granted in 2024 has converted to full approval, moving resmetirom past its confirmatory-data requirement in the outcomes trial that will keep running through 2028.

By AppliedXLJuly 16, 2026Trial NCT03900429

Executive Summary

Resmetirom's accelerated approval for MASH with fibrosis has converted to full FDA approval, resolving the contingency that has hung over the drug since 2024.
Full approval typically follows confirmatory evidence that verifies the clinical benefit the surrogate endpoint was meant to predict, closing out the regulatory question left open by the original accelerated approval.
The Phase 3 study behind the original approval is still active, running a longer-term outcomes measure through its primary completion date, and that confirmatory work now sits alongside a full approval rather than ahead of one.
Resmetirom remains the most advanced THR-beta agonist in MASH, with a nearer competitive set of GLP-1 and FGF21-pathway agents still running Phase 3 programs of their own.

The decision

Madrigal Pharmaceuticals, Inc. disclosed that the FDA approved Rezdiffra (resmetirom) for MASH with moderate to advanced fibrosis (F2 to F3) under a full approval action. Rezdiffra first won accelerated approval on March 14, 2024, when the FDA cleared resmetirom for noncirrhotic MASH with moderate to advanced liver fibrosis based on the 52-week biopsy portion of the MAESTRO-NASH trial. That earlier action rested on a surrogate endpoint: NASH resolution with no worsening of fibrosis, and fibrosis improvement with no worsening of NAFLD activity score, the two endpoints the FDA had proposed as reasonably likely to predict clinical benefit. Full approval represents the FDA's determination that the drug's benefit has since been verified rather than merely predicted. Madrigal+1

What the trial showed

The pivotal evidence behind the original approval came from MAESTRO-NASH (NCT03900429), a randomized, placebo-controlled Phase 3 study enrolling 1,759 patients with NASH and significant fibrosis (stages 2 and 3) across the United States, United Kingdom, and France. In the 52-week biopsy cohort, about 50% of patients on resmetirom 100 mg showed either NASH resolution or fibrosis improvement, and more than 80% showed fibrosis reversal or no fibrosis progression, against placebo. Lead investigator Stephen Harrison, chairman of Pinnacle Clinical Research and Summit Clinical Research, called MAESTRO-NASH "a landmark study in a disease that has historically been very challenging for drug development". NCT03900429+1

What stays open

MAESTRO-NASH itself has not closed. The trial is active but not recruiting, with a primary completion date of January 1, 2028, tracking a longer-horizon composite clinical outcome, time to a liver-related event such as hepatic decompensation, at 54 months. That outcomes measure is the confirmatory data the accelerated approval was designed to eventually verify, and it continues to run even as the regulatory question it was meant to answer has now been resolved by full approval. Madrigal also has a separate ongoing Phase 3 outcomes trial evaluating Rezdiffra in compensated MASH cirrhosis (F4c), a distinct and more advanced population from the fibrosis stage covered by this approval. NCT03900429+1

The competitive field

Resmetirom is one of two THR-beta agonists identified in active MASH-related development, the other being Nabiqasim Industries' Phase 4 resmetirom program and Viking Therapeutics' sobetirome, which is being tested in hypercholesterolemia rather than MASH. The broader MASH Phase 3 field is built on different mechanisms: Novo Nordisk's semaglutide and Boehringer Ingelheim's survodutide both target GLP-1 receptor pathways, while Akero Therapeutics' efruxifermin, 89bio's pegozafermin, and GlaxoSmithKline's efimosfermin alfa target FGF21-related pathways. None of those programs share resmetirom's THR-beta mechanism, which keeps the approved drug the only agent of its kind with a regulatory decision behind it in this indication.

This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.