Ocaliva won accelerated approval for primary biliary cholangitis in 2016, which the FDA refused to upgrade to full approval last year after an advisory committee was unable to verify a favorable risk/benefit profile.
Intercept Pharmaceuticals will take its liver disease drug Ocaliva off U.S. shelves, ending what has been a difficult road for the primary biliary cholangitis medication.
While Intercept continues “to believe the totality of clinical and real-world evidence” in support of Ocaliva’s safety and efficacy, it is pulling the drug from the U.S marketplace in compliance with a request from the FDA, Vivek Devaraj, the company’s U.S. president said in a statement on Thursday. “While our view of Ocaliva’s benefit-risk profile differs from FDA’s, we respect its request,” Devaraj continued, and the company has decided to withdraw the drug.
Alongside pushing for Ocaliva’s commercial exit, the FDA has also placed a clinical hold on clinical trials of obeticolhic acid—Ocaliva’s active ingredient—being conducted under a U.S. investigational new drug application.
Designed to be taken orally, Ocaliva is a small-molecule drug that activates the farnesoid X receptor, a modulator of a variety of cellular pathways, including those involved in metabolism, fibrosis and inflammation. The drug was granted accelerated approval in 2016 for primary biliary cholangitis, a rare and progressive autoimmune disease affecting the liver.
That regulatory win, however, has since been followed by a series of setbacks. Intercept has twice tried to expand Ocaliva into metabolic dysfunction-associated steatohepatitis (MASH), with both bids ending in failure: one in 2020 and another in 2023. Following the second rejection, Intercept gave up on its MASH aspirations and axed a third of its employees.
In September 2023, Intercept agreed to be acquired by Italian pharma Alfasigma for $800 million.
But the company’s problems didn’t end there. In September 2024, even Ocaliva’s accelerated approval was put at risk after the FDA’s staffers flagged safety concerns with the drug, noting that treatment resulted in “unfavorable trends” in death and liver transplantation rates. FDA reviewers at the time also argued that Ocaliva “failed to demonstrate efficacy” in one of its confirmatory trials.
These findings were presented in a briefing document ahead of a meeting of the regulator’s Gastrointestinal Drug Advisory Committee, which a few days later indeed voted against Ocaliva. The drug, according to the committee, was unable to verify a favorable risk/benefit profile in its confirmatory studies. The FDA went with the recommendations of its advisers and in November refused to grant Ocaliva full approval.
Then, last December, the FDA additionally revealed that it had detected instances of serious liver injury in patients who had been treated with Ocaliva. The agency also reported that in those for whom Ocaliva is indicated, treatment seems to worsen the risk of death or the need for liver transplantation.
