The U.S. Food and Drug Administration (FDA) has approved Rezdiffra (resmetirom) for the treatment of adults with non-alcoholic steatohepatitis (NASH) with moderate to advanced liver scarring (fibrosis). This marks a significant milestone as the first FDA-approved drug for NASH, a severe form of non-alcoholic fatty liver disease (NAFLD). Rezdiffra is intended to be used in conjunction with diet and exercise.
Mechanism of Action
Rezdiffra is a thyroid hormone receptor agonist that works by activating receptors in the liver. This activation helps to reduce fat accumulation, inflammation, and scarring, which are characteristic of NASH. “The drug is a targeted therapy that directly addresses the metabolic dysfunction in the liver in patients with metabolic dysfunction-associated steatohepatitis (MASH),” explains Dr. James Burton, a transplant hepatologist at UCHealth and faculty member at the University of Colorado School of Medicine.
Clinical Trial Results
The approval was based on data from a 54-month, randomized, double-blind, placebo-controlled trial. The trial evaluated the safety and efficacy of Rezdiffra in patients with NASH and moderate to advanced liver fibrosis. Participants were randomly assigned to receive either a placebo, 80 mg of Rezdiffra, or 100 mg of Rezdiffra once daily, in addition to standard care, including counseling on healthy diet and physical activity.
After 12 months, liver biopsies showed that a significantly greater proportion of subjects treated with Rezdiffra achieved NASH resolution or an improvement in liver scarring compared to those who received a placebo. Specifically, up to 36% of those who received Rezdiffra experienced NASH resolution and no worsening of liver scarring, compared to 9-13% in the placebo group. Additionally, up to 28% of people who received Rezdiffra experienced an improvement in liver scarring and no worsening of NASH, compared to 13-15% of those who received a placebo.
The FDA granted Rezdiffra accelerated approval, which allows for earlier approval of drugs that treat serious conditions and address an unmet medical need. The manufacturer is required to conduct a post-approval study to verify the drug’s clinical benefit by completing the 54-month study currently ongoing.
Safety and Tolerability
The most common side effects observed in clinical trials were diarrhea and nausea. The drug also carries a warning for potential drug-induced liver toxicity and gallstones or gallbladder/pancreas inflammation. Rezdiffra is contraindicated in patients with severe liver damage (cirrhosis) and should be used with caution in patients taking statins.
Considerations for Use
Dr. Burton notes that the FDA limited the drug to those with stages 2 and 3 fibrosis but did not specify how to determine who has this degree of fibrosis. He recommends a biopsy in anyone with suspected MASH who might be suspected of having advanced fibrosis on non-invasive testing to ensure an accurate baseline.
Cost and Access
The cost of Rezdiffra is approximately $46,000 per year. The manufacturer offers a Copay Savings Card to help offset the cost, potentially reducing the monthly expense for eligible patients to as little as $10. It's important to note that Rezdiffra is not a replacement for a healthy lifestyle, especially when it comes to weight loss and control of type 2 diabetes.
Implications for NASH Treatment
The approval of Rezdiffra represents a significant advancement in the treatment of NASH, offering a new therapeutic option for patients with this progressive liver disease. While Rezdiffra is an effective treatment for fatty liver and scarring, it is generally well-tolerated. If you’ve been diagnosed with fatty liver disease with moderate to advanced scarring without cirrhosis, you might want to speak with your doctor about whether Rezdiffra could be a helpful addition to a healthy lifestyle.
