Rezdiffra Approved for MASH

The first drug for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) – formerly known as non-alcoholic steatohepatitis (NASH) – was granted Accelerated Approval by the U.S. Food and Drug Administration (FDA) on March 14, 2024. Madrigal Pharmaceuticals’ Rezdiffra^™ (resmetirom) is a thyroid hormone receptor-beta (THR-beta) agonist indicated along with diet and exercise for the treatment of adults who have noncirrhotic MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis). The recommended oral, once-per-day dose is 80mg for patients who weigh less than 100kg (220 pounds) and 100mg for patients who weigh 100kg or more. It will be available through a large network of specialty pharmacies that includes Accredo. Madrigal has indicated that Rezdiffra will be available in April 2024 with a wholesale acquisition cost (WAC) of $47,400 per year. For full prescribing information, see here.

At a Glance

• Brand (Generic) Name: Rezdiffra (resmetirom)
• Manufacturer: Madrigal Pharmaceuticals
• Date Approved: March 14, 2024                                                                                                                                               
• Indication: for the treatment of adults who have MASH with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis) along with diet and exercise
• Dosage Forms Available: 60mg, 80mg and 100mg oral tablets
• Launch Date: April 2024
• Estimated Cost: WAC of $47,400 per year
• MASH, which damages liver cells (fibrosis) and causes inflammation, is a severe and more progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), the new name for non-alcoholic fatty liver disease (NAFLD). Neither condition has definite symptoms, so they may not be diagnosed until damage is extensive. Liver fibrosis is staged in ranges from F0 (no fibrosis) to the most severe F4 (cirrhosis).
• Although MASH is very similar to liver disease caused by excessive alcohol consumption, it occurs in patients who drink little or no alcohol. Developing the condition is highly associated with several metabolic conditions that include obesity, type 2 diabetes, hypertension, and high cholesterol.
• An estimated  6 million to 8 million people in the U.S. have MASH with moderate to advanced liver scarring.
• No other drugs are FDA-approved to treat MASH. As a result, the first line of treatment for them includes diet modification, increased physical activity, and weight loss.
• In its phase III, pivotal study (MAESTRO-NASH), Rezdiffra showed significant improvement in liver scarring (measured by liver biopsy) compared to placebo. At 12 months, a total of 27% (80mg) and 36% (100mg) of patients saw the resolution of MASH and no worsening of liver scarring vs. 13% of those who received placebo and counseling for diet and exercise. 
• While a liver biopsy is the only definitive test for diagnosis, most healthcare professionals can diagnose MASH using non-invasive imaging techniques. The label for Rezdiffra does not require a liver biopsy for diagnosis.
• The most common adverse events (AEs) include diarrhea, nausea, pruritus, stomach pain, vomiting, constipation, and dizziness. It also comes with warnings for possible liver toxicity and gallbladder problems.
• Rezdiffra was approved under Accelerated Approval, so continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. It also received designations as a Breakthrough Therapy, Fast Track, and Priority Review.