With a Friday advisory committee meeting looming, the sole indication for Intercept Pharmaceuticals’ Ocaliva appears to be at risk as the regulator flags issues regarding its post-marketing results.
The FDA could pull the accelerated approval for Intercept Pharmaceuticals’ Ocaliva (obeticholic acid) for primary biliary cholangitis, as the agency cites problems with post-marketing data ahead of an advisory committee meeting.
The regulator will convene its Gastrointestinal Drugs Advisory Committee on Friday to discuss the matter.
In the meantime, the FDA’s internal staffers released a briefing document outlining the agency’s concerns regarding Ocaliva. In one of its confirmatory trials, dubbed 747-302, Ocaliva “failed to demonstrate efficacy” on the primary composite endpoint of liver transplantation, death and other liver-related outcomes. The study focused on primary biliary cholangitis (PBC) patients with chronic disease.
The FDA’s analysis of 747-302’s data also showed that Ocaliva led to “unfavorable trends” in liver transplantation and mortality.
An observational cohort study with real-world evidence that Intercept submitted to bolster Ocaliva’s case also “did not demonstrate clinical benefit” compared to PBC patients who were not being treated with Ocaliva.
The third study under contention is another post-marketing confirmatory trial dubbed 747-401, which was designed to evaluate the pharmacokinetic and pharmacodynamic profiles of Ocaliva in PBC patients with Child-Pugh classes B and C. However, while the study was ongoing, the FDA flagged reports of hepatotoxicity associated with Ocaliva, which led to substantial changes in the drug’s boxed warning and safety labels.
“As a result of this regulatory action, Trial 747-401 was terminated because OCA was now contraindicated for the entire study population,” the FDA staffers wrote in the briefing document. Some patients in the747-302 study also had to drop out because of this labelling adjustment, though the regulator contends that “it reached study closure and achieved the target number of events” for an analysis of its efficacy endpoint.
The advisory committee will deliberate on whether the findings from the observational study and the 747-302 trial are enough to confirm the clinical benefit of Ocaliva in PBC, or if Intercept needs to run additional studies. Given its safety signals, the panel will also discuss whether Ocaliva’s clinical benefits outweigh its risks.
Ocaliva is a farnesoid X receptor agonist that works by preventing the build-up of bile acid in the liver. The FDA granted it accelerated approval in 2016 for PBC. Intercept has tried and twice failed to secure approval in metabolic dysfunction-associated steatohepatitis (MASH)—the first in June 2020 and then again in June 2023—which forced the company to abandon its MASH program and lay off one-third of its staff.
Shortly after, Italian pharma Alfasigma acquired Intercept for $800 million.
