FDA calls expert hearing for Intercept's high-profile NASH application for Ocaliva

As many market watchers expected, the FDA is calling for external input on Intercept Pharmaceuticals’ nonalcoholic steatohepatitis (NASH) candidate. But given a competitor’s recent clinical trial win, analysts have predicted a tough discussion ahead.

The FDA will convene a one-day meeting of its Gastrointestinal Drugs Advisory Committee on May 19 to discuss Intercept’s application for the oral drug obeticholic acid in NASH-related pre-cirrhotic liver fibrosis, according to a federal registry post (PDF).

The agency previously accepted Intercept’s application and set a target decision date of June 22.

Obeticholic acid, or OCA, is currently sold at lower dosages under the brand name Ocaliva as a treatment for primary biliary cholangitis, another liver disease. If everything goes according to Intercept’s plan, Ocaliva could become the first FDA-approved NASH therapy.

An advisory committee hearing was largely expected given that the FDA had once rejected Ocaliva in NASH. 

The FDA shot down Ocaliva’s first NASH bid in 2020. Intercept then changed its phase 3 analysis to use a central consensus reading of liver biopsy instead of relying on each trial center’s own evaluation. The new data package also included a longer follow-up for safety.

The FDA’s views on Intercept’s second bid remain unclear. An advisory committee meeting could provide much-needed clarity on the agency’s stance, SVB Securities analysts said in a note last week. However, the SVB team saw a tough discussion ahead for Intercept given Madrigal Pharmaceuticals’ recent phase 3 NASH win.

In December, Madrigal said its candidate resmetirom achieved statistically significant improvement on both liver scarring and, perhaps more importantly, NASH resolution against placebo. As the SVB team noted at the time, the phase 3 Maestro-NASH results made resmetirom the first therapeutic to show improvements on both fronts.

The readout exceeded expectations and established Madrigal as “the clear leader” in NASH, SVB said in a December note. Madrigal has said it plans to file for FDA approval by June.

For its part, Intercept’s Ocaliva outperformed placebo in helping more patients with pre-cirrhotic NASH achieve at least one stage of liver fibrosis improvement with no worsening of NASH. However, the drug failed to significantly resolve NASH.

In addition, Ocaliva recently failed in more severe cirrhotic NASH patients. Although Intercept has said the two treatment settings won’t affect each other, analysts at SVB said they suspected the FDA might draw some inferences from the failed cirrhotic trial.

With everything known about the two drugs to date, SVB projected Ocaliva’s peak NASH sales will hit $806 million. The team figured resmetirom could hit $2.5 billion at peak.

Ahead of any FDA decisions, the drug cost watchdogs at the Institute for Clinical and Economic Review recently said resmetirom looks more cost-effective than Ocaliva in NASH. The finding came in the form of a draft report.

Meanwhile, Intercept has already started commercial preparations for a potential launch in NASH. Intercept has been talking to payers about pricing and reimbursement, chief commercial officer Linda Richardson said on the company's fourth-quarter earnings conference call. Nearly three out of four of the top potential prescribers for NASH are already within Ocaliva’s network in primary biliary cholangitis, she said.