FDA Approves Rezdiffra for Nonalcoholic Steatohepatitis With Liver Fibrosis

The Food and Drug Administration (FDA) has granted accelerated approval to Rezdiffra^™ (resmetirom) in conjunction with diet and exercise for the treatment of adults with noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis).

Rezdiffra is an oral thyroid hormone receptor (THR)-β selective agonist. The approval was based on data from the phase 3 MAESTRO-NASH study (ClinicalTrials.gov Identifier: NCT03900429), which evaluated the efficacy and safety of resmetirom in patients with biopsy-proven NASH and fibrosis who were on stable doses of medications for diabetes, dyslipidemia, and hypertension.

Study participants were randomly assigned to receive resmetirom 80mg (n=298), resmetirom 100mg (n=296), or placebo (n=294) once daily, in addition to lifestyle counseling on nutrition and exercise. The dual primary surrogate endpoints were NASH resolution with at least a 2-point reduction in nonalcoholic fatty liver disease (NAFLD) activity score, and with no worsening of fibrosis or at least a 1-stage improvement in fibrosis with no worsening of the NAFLD activity score after 52 weeks of treatment. 

Findings showed a total of 26% to 27% of patients treated with resmetirom 80mg and 24% to 36% of patients treated with resmetirom 100mg achieved NASH resolution and no worsening of liver fibrosis compared with 9% to 13% of those who received placebo. The range of responses were based on readings from 2 pathologists. 

Moreover, 23% of patients treated with resmetirom 80mg and 24% to 28% of patients treated with resmetirom 100mg achieved at least a 1-stage improvement in liver fibrosis with no worsening of steatohepatitis compared with 13% to 15% of the placebo group. Greater reductions were also observed in average alanine transaminase (ALT) and aspartate transaminase (AST) in the resmetirom groups starting at month 3 through month 12 vs the placebo group.

The most common adverse reactions reported with treatment included diarrhea, nausea, pruritus, vomiting, constipation, abdominal pain, and dizziness.

“Previously, patients with NASH who also have notable liver scarring did not have a medication that could directly address their liver damage,” said Nikolay Nikolov, MD, acting director of the Office of Immunology and Inflammation in the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Rezdiffra will, for the first time, provide a treatment option for these patients, in addition to diet and exercise.”

Rezdiffra is supplied in 60mg-, 80mg-, and 100mg-strength tablets and is expected to be available in April 2024 through a limited specialty pharmacy network. 

Rezdiffra is approved under accelerated approval based on improvement of NASH and fibrosis. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.