US panel backs Intercept's Ocaliva for primary biliary cholangitis

An FDA advisory committee voted 17 to 0 on Thursday to recommend accelerated approval for Intercept Pharmaceuticals' Ocaliva (obeticholic acid) as a potential treatment for patients with primary biliary cholangitis (PBC). Company shares gained about 11 percent on the news. The US regulator is scheduled to make a decision on whether to approve the experimental oral drug by May 29.

The vote follows an FDA staff review released earlier this week that had identified no major concerns regarding farnesoid X receptor agonist for use in PBC. The agency was seeking advice from the panel on whether alkaline phosphatase (ALP), an enzyme that the drug reduces, is a "reasonably likely" predictor of improved outcomes. However, while advisory committee members agreed that the short-term ALP measure of liver function was sufficient as a surrogate to predict long-term benefit, some noted the lack of direct efficacy evidence for the drug in PBC. Still, one panelist acknowledged that "it's not the best [marker], but it's the best we have."

The panel also supported Intercept's proposed administration of Ocaliva, which starts with a 5-mg daily dose and progresses to 10 mg after several months if the patient tolerates the drug. However, at least one panel member said the incidence of mild liver-related events reported in some patients taking the higher dose should be followed long-term in post-approval studies, if the FDA approves the drug. "Weighing the risks and benefits in the setting of patients with PBC, with limited treatment options, I think it's very reasonable to go forward," stated panelist Linda Feagins.

Intercept is seeking to have Ocaliva approved for PBC in patients unsuitable for treatment with ursodeoxycholic acid (UDCA), which it noted is the only approved therapy for the disease. The company said the advisory panel based its recommendation in part on data from the Phase III POISE trial, which evaluated Ocaliva in 216 PBC patients who had an inadequate therapeutic response to, or were unable to tolerate, UDCA. Meanwhile, enrollment is currently underway in the long-term COBALT outcomes trial to confirm the clinical benefit of Ocaliva in patients with PBC.

Wedbush Securities analyst Liana Moussatos said recently that "if approved, we project launch in July and gross peak annual worldwide sales could reach about $2.2 billion." In December, Intercept said the FDA had extended the decision date for the drug, which is also referred to as OCA, in the PBC indication by three months to May 29. "In response to an information request from the FDA, additional clinical data analyses have been submitted," Intercept stated at the time. The company has also applied for Ocaliva to obtain EU marketing approval in the same indication.

Meanwhile, Intercept is conducting late-stage testing of the therapy in patients with nonalcoholic steatohepatitis (NASH). In 2014, the Phase IIb FLINT trial was stopped early on positive data for the drug to treat patients with NASH. Concerns were later raised about a safety signal related to lipid dysregulation, and Intercept has since also reported a positive update to the FLINT trial.

Other companies developing drugs for NASH include Gilead Sciences, GenFit, Tobira Therapeutics and Conatus Pharmaceuticals. Earlier this week, Gilead agreed to acquire Nimbus Therapeutics' Nimbus Apollo unit and its acetyl-CoA carboxylase inhibitor programme focused on the treatment of NASH for up to $1.2 billion.

For related analysis, see ViewPoints: Investors wanting a big deal forced to settle for Gilead's long game in NASH. See also ViewPoints: Intercept putting all its ducks in a row for OCA – and beyond.

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