FDA Approves Rezdiffra, First Drug for NASH

The FDA announced today that it had granted accelerated approved for Rezdiffra (resmetirom), the first drug approved for noncirrhotic non-alcoholic steatohepatitis (NASH).

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

The safety and efficacy of Rezdiffra was evaluated based on an analysis of a surrogate endpoint at month 12 in a 54-month, randomized, double-blind placebo-controlled trial, according to an FDA news release.

The drug’s maker, Madrigal Pharmaceuticals in West Conshohocken, Philadelphia, is required to conduct a postapproval study to verify that the surrogate marker translates into clinical benefit.

Bill Sibold, MBA

During an investors conference call late this afternoon, Madrigal CEO Bill Sibold, MBA, said the new drug would be priced at the wholesale acquisition cost (WAC) price of $47,400 per year. That is the at the high end of the $39,600-$50,100 range that the Institute for Clinical and Economic Review, an independent cost-effectiveness research group, set for the drug if it were to meet commonly accepted cost-effectiveness thresholds.

“This is a high value medicine that has a significant burden on patients and the healthcare system," Sibold.

Sibold called the FDA-approved label for “a very clean, very clear label” with no boxed safety warnings or contradictions. He and others on the call highlighted that the label does not require biopsies for a diagnosis of moderate or advanced NASH. Instead, patients can be diagnosed with noninvasive ultrasound imaging (FibroScan) or blood tests that biomarkers of liver fibrosis that circulate in the blood (Enhanced Liver Fibrosis). The patients enrolled in the MAESTRO-NASH phase 3 trial on which the approval was based their NASH diagnoses confirmed by biopsy..

“A biopsy for diagnosis is rarely used in the real world. It’s not standard of care. And I was pleased to see that the FDA didn’t include it as a requirement in the Rezdiffra label,” Stephen A. Harrison, M.D., said on the conference call. Harrison was the principal lead investigator on the MAESTRO-NASH trial.

Harrison said the majority of NASH specialists have access to such noninvasive tests. Several of the questions during the question-and-answer part of the investors calls were about the noninvasive tests, their availability and coverage.

Stephen Harrison, MBA

According to Harrison, patients with NASH — which some experts are now calling metabolic dysfunction-associated steatohepatitis, or MASH — have been treated with suggestions for improved diet and getting more exercise and medications to treat conditions associated with NASH, primary diabetes and cardiovascular disease.

“These interventions are not liver directed, and have not delivered a fibrosis benefit,” Harrison said during the call. The approval of Rezdriffa, he said, “changes the paradigm” to drug that works directly in the liver and reverses fibrosis.

“I feel like it's Christmas in March,” said Harrison. “You know as a treater of Nash for the last 25 years, it's an incredibly exciting day to see the first medicine approved for NASH.”