Today, the U.S. Food and Drug Administration has given its approval for Rezdiffra (resmetirom) to be used in the treatment of noncirrhotic non-alcoholic steatohepatitis (NASH) in adults who have moderate to advanced liver scarring (fibrosis). This medication is intended to be used alongside diet and exercise.

Addressing an Unmet Medical Need

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

The Significance of NASH

NASH is a consequence of the progression of nonalcoholic fatty liver disease, where liver inflammation over time can lead to liver scarring and dysfunction. It is often linked with other health issues such as high blood pressure and type 2 diabetes. Statistics indicate that approximately 6-8 million individuals in the U.S. have NASH with moderate to advanced liver scarring, and this number is expected to rise.

Efficacy of Rezdiffra

Rezdiffra, a partial activator of a thyroid hormone receptor, works by reducing liver fat accumulation. Its safety and efficacy were assessed in a 54-month, randomized, double-blind placebo-controlled trial, which evaluated a surrogate endpoint at month 12 measuring the extent of liver inflammation and scarring.

Highlights

In the trial, 888 subjects were randomly assigned to receive placebo or varying doses of Rezdiffra, in addition to standard care for NASH. At 12 months, liver biopsies revealed that a greater proportion of those treated with Rezdiffra experienced NASH resolution or an improvement in liver scarring compared to those on placebo.

The most common side effects of Rezdiffra include diarrhea and nausea. However, it comes with warnings, such as drug-induced liver toxicity and gallbladder-related side effects. Patients with decompensated cirrhosis should avoid its use, and caution is advised when using it alongside certain other drugs, particularly statins for cholesterol reduction.

Accelerated Approval Pathway

Rezdiffra received approval under the accelerated approval pathway, which enables earlier approval of drugs addressing serious conditions and unmet medical needs based on surrogate or intermediate clinical endpoints that predict clinical benefit. A 54-month study, still ongoing, will further assess its clinical benefit.

Breakthrough Therapy Designation

Rezdiffra was granted Breakthrough Therapy, Fast Track, and Priority Review designations for this indication. The FDA has entrusted the approval of Rezdiffra to Madrigal Pharmaceuticals.