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REZDIFFRA (resmetirom) is a first-in-class thyroid hormone receptor-beta (THR-β) agonist approved for the treatment of noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis (F2–F3). It selectively activates hepatic THR-β, reducing intrahepatic lipid accumulation, inflammation, and fibrosis while minimizing systemic effects. Approval under the FDA’s accelerated pathway is based on histopathologic improvement; confirmatory trials are required to verify clinical outcomes such as reduced cirrhosis-related morbidity.
Key considerations include weight-based dosing, monitoring for hepatotoxicity and gallbladder adverse events, and avoidance in decompensated cirrhosis. Common adverse reactions (e.g., diarrhea, nausea) are manageable, but drug interactions with CYP2C8 inhibitors and statins necessitate dose adjustments or avoidance. Resmetirom represents a targeted therapeutic advance for a condition with previously limited treatment options.
REZDIFFRA is indicated 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).
Accelerated Approval: Based on improvement in liver histology (NASH resolution and fibrosis improvement). Continued approval is contingent on verification of clinical benefit in confirmatory trials.
Weight-Based Dosing:
<100 kg: 80 mg once daily.
≥100 kg: 100 mg once daily.
Dosage Adjustments:
Strong inhibitors (e.g., gemfibrozil): Avoid concomitant use.
Moderate inhibitors (e.g., clopidogrel): Reduce dose to 60 mg (<100 kg) or 80 mg (≥100 kg).
