Is the first NASH drug approval nearing? Intercept stages comeback as FDA sets decision date 

A treatment for non-alcoholic steatohepatitis may finally be around the corner—and contender Intercept Pharmaceuticals hopes it won’t disappoint for a second time.

Intercept’s obeticholic acid has moved one step closer toward its goal of becoming the first NASH therapy in the U.S. The FDA has accepted Intercept’s latest application for the drug in patients with NASH-related pre-cirrhotic liver fibrosis, the company said Thursday.

The FDA has set a target decision date of June 22, 2023, although Intercept cautioned that the review timeline may be subject to change. Intercept is seeking an accelerated approval.

Intercept didn’t mention whether the FDA plans an advisory committee meeting for the application. In an email to Fierce Pharma, a spokesperson said the company has no additional information to share at this point, and that it will make further announcement once it hears more from the FDA. During the company’s third-quarter earnings call in November, R&D chief Michelle Berrey, M.D., said Intercept expects the FDA to convene such a meeting in the spring.

In a note following the call, SVB Securities analysts said an approval is unlikely mainly because of uncertainties around the drug’s safety analysis. But if the drug can reach the market in NASH fibrosis, Ocaliva could generate significant sales in the indication, the team said.

Obeticholic acid is currently sold under the brand name Ocaliva as a medication for primary biliary cholangitis. Back in 2020, the FDA rejected Intercept’s plan to repurpose Ocaliva for NASH. Afterward, Intercept came back with a reanalysis of the phase 3 REGENERATE trial and resubmitted its medicine in December. Obviously, the FDA thinks the new data are at least adequate to warrant a review.

In the updated analysis, the REGENERATE trial showed that Ocaliva, given once-daily at 25 mg, topped placebo and helped patients with advanced but pre-cirrhotic NASH achieve at least one stage of liver scarring improvement with no worsening of NASH after 18 months.

Improvement in liver histology is just one of two primary endpoints of REGENERATE, and it only supports Ocaliva’s bid for an accelerated approval. The trial remains ongoing—with 2,480 randomized participants—to collect data on all-cause death and liver-related clinical outcomes as the other primary endpoint. Those data on clinical benefit, if positive, could support a full approval.

The FDA’s acceptance of Intercept’s application in non-cirrhotic NASH also comes after Ocaliva failed a trial in patients with more advanced disease who have developed cirrhosis. Intercept has said the two settings won’t affect each other, but SVB analyst Thomas Smith disagrees.

In its November note, the SVB team argued that detailed safety data from the failed phase 3 REVERSE trial in cirrhotic NASH “will be of interest to FDA” in reviewing the non-cirrhotic application. When Intercept announced the REVERSE trial failure in September, SVB singled out patients who reached and were maintained at the 25 mg dosing level in that study. The analyst said the drug's safety profile in those patients “will be key to any potential path forward” for Ocaliva in advanced fibrotic NASH.

No NASH therapy is available in the U.S. today. Ocaliva could be the first if the FDA approves it on time. But potential competition may not be too far behind. Madrigal Pharmaceuticals is on track to file its lead candidate resmetirom for an accelerated approval in NASH after hitting liver histological goals in a phase 3 study.