FDA Approves Rezdiffra (resmetirom) for NASH with Liver Fibrosis
Key Insights
The FDA has granted accelerated approval to Rezdiffra (resmetirom) for treating noncirrhotic NASH (search) with moderate to advanced liver fibrosis (search).
Rezdiffra is a thyroid hormone receptor-β agonist, administered orally, and aims to reduce liver fat accumulation and inflammation.
The approval is based on Phase 3 MAESTRO-NASH (search) trial data demonstrating NASH resolution and fibrosis improvement.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Rezdiffra (resmetirom) for the treatment of adults with noncirrhotic nonalcoholic steatohepatitis (NASH (search)) with moderate to advanced liver fibrosis (search) (consistent with stages F2 to F3 fibrosis). This marks a significant milestone as it is the first FDA-approved therapy specifically for NASH, a severe form of nonalcoholic fatty liver disease (NAFLD (search)).
Rezdiffra is a thyroid hormone receptor-β (THR-β (search)) agonist. It is designed to target key underlying causes of NASH (search). The drug works by activating THR-β in the liver, which helps to reduce liver fat accumulation, inflammation, and fibrosis. The recommended dosage is an oral tablet taken once daily, with or without food. The dosage is based on actual body weight.
Clinical Efficacy and Safety
The approval was based on data from the pivotal Phase 3 MAESTRO-NASH (search) trial. This trial evaluated the efficacy and safety of resmetirom in patients with biopsy-confirmed NASH and liver fibrosis (search). The study included a diverse patient population, and key findings demonstrated that resmetirom led to statistically significant improvements in NASH resolution and fibrosis reduction compared to placebo.
Specifically, the MAESTRO-NASH (search) trial met its primary endpoints, showing that resmetirom achieved NASH resolution (defined as no NASH and no worsening of liver fibrosis (search)) and liver fibrosis improvement (at least a one-stage reduction in fibrosis without worsening of NASH). These improvements were observed in a significant proportion of patients treated with resmetirom compared to those receiving placebo.
The most common adverse reactions reported in clinical trials included diarrhea and nausea. The prescribing information includes warnings and precautions for hepatotoxicity and gallbladder-related adverse reactions.
Accelerated Approval Pathway
It is important to note that the approval is an accelerated approval, meaning that continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. This highlights the FDA's commitment to providing timely access to promising therapies while ensuring ongoing evaluation of their long-term benefits.
The Evolving Landscape of Fatty Liver Disease
NAFLD (search) is a spectrum of conditions characterized by the buildup of fat in the liver. NASH (search) is a more severe form of NAFLD, marked by liver inflammation and damage, which can lead to fibrosis, cirrhosis (search), and liver failure. Recently, there has been a movement to update the nomenclature of fatty liver diseases, with terms like metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) being proposed to better reflect the underlying causes and disease mechanisms.