Intercept's NASH dreams may be dashed after FDA panel votes against Ocaliva's approval bid

It looks like Intercept Pharmaceuticals’ Ocaliva still has a tough road ahead in nonalcoholic steatohepatitis (NASH) after a panel of FDA advisers voiced concerns with the company's application package.

During a one-day meeting of the FDA’s Gastrointestinal Drugs Advisory Committee, panelists voted 12 to 2—with two abstentions—that the benefits of Ocaliva 25 mg, also known as obeticholic acid, or OCA, don’t outweigh the risks in NASH patients with stage 2 or 3 fibrosis.

Further, in response to the question about a potential accelerated approval, panelists voted 15 to 1 against that regulatory pathway for the drug.

Many of the naysayers' concerns came down to Intercept’s use of a surrogate endpoint in its clinical trial. Panelists' concerns also centered on the potential for OCA to cause drug-induced liver injury.

While the FDA isn’t beholden to the advice of its advisory committees, the regulator often follows its experts’ lead. Intercept’s NASH candidate Ocaliva is up for an approval decision by June 22.

The drug is already sold as a treatment for primary biliary cholangitis, another liver disease. If Intercept ultimately snags approval, its med will become the first FDA-approved NASH therapy.

In clinical trials, 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.

Ocaliva has already struggled in NASH once. Back in 2020, the FDA rejected the drug’s bid for approval in the confounding liver disease. 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 company’s latest data package also includes a longer follow-up study for safety.

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