FDA Approves First Treatment for Adults With NASH, Serious Liver Disease

On March 14, the FDA approved resmetirom for the treatment of adults with noncirrhotic non-alcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis. The FDA recommended that resmetirom should be used while also maintaining a healthy diet and exercise.

“Previously, patients with NASH who also have notable liver scarring did not have a medication that could directly address their liver damage,” Nikolay Nikolov, MD, acting director of the Office of Immunology and Inflammation in the FDA’s Center for Drug Evaluation and Research said in a press release.

Approximately 6 million to 8 million people in the United States have NASH with moderate-to-advanced liver scarring—and that number is expected to rise in the coming years. Generally, NASH is associated with high blood pressure and type 2 diabetes. But importantly, resmetirom is a partial activator of a thyroid hormone receptor. When this receptor is activated by resmetirom in the liver, studies have shown a reduction in liver fat accumulation.

Researchers examined the safety and efficacy of resmetirom based on an analysis of a surrogate endpoint, which measured the extent of liver inflammation and scarring at 12 months in a 54-month, randomized, double-blind placebo-controlled trial.

In the trial, 888 subjects were randomly assigned to receive either a placebo (n = 294); 80 mg of resmetirom (n = 298); or 100 mg of resmetirom (n = 296) once daily, in addition to standard care for NASH (counseling for healthy diet and exercise).

Looking at liver biopsies at 12 months, the results showed that a greater proportion of those who were treated with resmetirom achieved NASH resolution or an improvement in liver scarring compared with those who received the placebo. Indeed, 26% to 27% of those who received 80 mg and 24% to 36% of those who received 100 mg of resmetirom had NASH resolution and no worsening of liver scarring compared with 9% to 13% of those who received placebo and counseling on diet and exercise. Additionally, those who received resmetirom showed a greater improvement in liver scarring compared with the placebo group.

“Demonstration of these changes in a proportion of patients after just 1 year of treatment is notable, as the disease typically progresses slowly with a majority of patients taking years or even decades to show progression,” the FDA noted in a press release.

The most common side effects for resmetirom include diarrhea and nausea, and the treatment should be avoided in patients with decompensated cirrhosis. Patients using resmetirom while taking statins for lowering cholesterol may result in drug interactions.

Reference
FDA approves first treatment for patients with liver scarring due to fatty liver disease. News release. US Food and Drug Administration; March 14, 2024. Accessed March 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease