FDA Believed Poised to Approve First Med for a Serious Liver Disease

WASHINGTON — The Food and Drug Administration appears poised to approve the first medicine developed specifically to treat the serious liver disease known as MASH later this week. 

Metabolic dysfunction-associated steatohepatitis — formerly known as nonalcoholic steatohepatitis — is often associated with obesity.

In patients who have it, the accumulation of fat in the liver causes inflammation, which leads to fibrosis, or liver scarring, and can progress in more advanced stages to cirrhosis, cancer and the need for a liver transplant.

Currently, there are no FDA-approved therapies available for its treatment. But that could end as soon as Thursday, when the agency is expected to wrap up a priority review of a pill called resmetirom, manufactured by Madrigal Pharmaceuticals.

Resmetirom is a once-daily, oral, liver-directed THR-β agonist designed to target key underlying causes of the progressive disease. It was initially developed as a medication for lowering the levels of unhealthy lipids in the body such as cholesterol.

Earlier this month, Madrigal Pharmaceuticals announced its marketing authorization application for resmetirom had been validated and was under evaluation with the European Medicines Agency’s Committee for Medicinal Products for Human Use.

Here in the US, resmetirom was granted a “breakthrough therapy” designation from the FDA and its priority review was granted under the Prescription Drug User Fee Act, which established the target date for completion of the review.

The clinical development program for resmetirom consisted of 18 clinical studies supporting the MAA: 12 Phase 1 studies, two Phase 2 studies, and four Phase 3 studies. 

The pivotal MAESTRO-NASH trial of resmetirom was the only Phase 3 trial in NASH to achieve both fibrosis reduction and NASH resolution primary endpoints.

“[MASH] with fibrosis represents a serious burden for both patients and health systems. Without treatment, the disease can lead to cirrhosis, liver failure, liver cancer and premature death,” said Dr. Becky Taub, chief medical officer and president of research and development for Madrigal. 

“Based on the positive results from our Phase 3 MAESTRO trials, we believe resmetirom has the potential to become the first therapy for patients with [MASH] with liver fibrosis to receive approval in Europe,” Taub’s written statement said.

Madrigal estimates approximately 1.5 million patients have been diagnosed with MASH in the U.S., and approximately 525,000 have MASH with significant fibrosis. 

Madrigal plans to focus on approximately 315,000 diagnosed patients with MASH with significant fibrosis under the care of the liver specialist physicians during the launch of resmetirom.

“As we near an FDA decision on accelerated approval of resmetirom in the U.S. and advance our application in Europe, Madrigal is generating new momentum for the [MASH] field,” said Bill Sibold, chief executive officer of Madrigal, in a written statement. 

“The results from our pivotal Phase 3 trial recently published in the New England Journal of Medicine provide a robust dataset to support regulatory evaluation globally, and our two ongoing outcomes trials carry the potential to reinforce Madrigal’s long-term leadership position in [MASH],” he continued. “Our regulatory, R&D and commercial activities continue to accelerate, and each day brings us one step closer to delivering the first foundational therapy to patients with this serious disease.”

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