After years of regulatory hurdles, Intercept Pharmaceuticals is pulling its liver disease drug Ocaliva (obeticholic acid) from the U.S. market following a request from the Food and Drug Administration (FDA).
The FDA has placed Intercept’s clinical trials of obeticholic acid on hold and asked the company to voluntarily withdraw the medicine, which has been approved since 2016 under the agency’s accelerated approval program for certain patients with primary biliary cholangitis (PBC).
In a press release, Intercept confirmed that it would comply with the FDA’s request. “While our view of Ocaliva’s benefit-risk profile differs from the FDA’s, we respect its request and have made this difficult decision to provide clear guidance for patients and prescribers,” said Intercept’s U.S. president Vivek Devaraj. He added that the company remains committed to advancing innovation in hepatology and serving patients and physicians.
The decision comes after a series of setbacks for Ocaliva. In 2023, the FDA’s Gastrointestinal Drug Advisory Committee voted strongly against Intercept’s data package, expressing concerns about safety and efficacy. The FDA also noted in its briefing materials that Ocaliva could increase the risk of liver transplant or death in patients. Following the committee’s vote, the agency declined to grant full approval but allowed the drug to remain on the market for certain patients under its accelerated approval while it reviewed additional safety data.
Despite those conditions, the regulator has now concluded that the risks outweigh the benefits. Intercept stated that the FDA has also imposed a clinical hold on all U.S. trials involving obeticholic acid.
Ocaliva, chemically known as obeticholic acid, received accelerated approval in 2016 for the treatment of PBC, a rare liver disease that damages the bile ducts and can progress to liver failure. Under this pathway, drugmakers are required to conduct post-market studies to confirm clinical benefits. If those studies fail to demonstrate sufficient efficacy or reveal new safety risks, the FDA can request withdrawal.
In 2021, the FDA had already restricted Ocaliva’s use in patients with advanced cirrhosis or liver scarring. By December 2023, the agency reported it was studying cases of liver injury in patients without advanced disease.
The U.S. withdrawal follows regulatory challenges for Ocaliva outside the country as well. European regulators revoked the drug’s marketing authorization in late 2023 after a holding period.
Ocaliva was once considered a key growth driver for Intercept. The company had previously sought approval of the drug as a treatment for nonalcoholic steatohepatitis (NASH), now referred to as metabolic dysfunction-associated steatohepatitis (MASH). However, the FDA twice declined approval for that indication, leading Intercept to abandon the program, reduce its workforce, and shift focus to PBC. The company was later acquired by Italian pharmaceutical firm Alfasigma in a deal worth about $800 million.
Ocaliva has been Intercept’s only marketed product, generating $285.7 million in sales in 2022. Beyond obeticholic acid, Intercept has one next-generation FXR agonist in development, currently in a phase 2a trial for severe alcohol-associated hepatitis.
The company said it will provide additional information to healthcare professionals and patients as it coordinates with the FDA on the transition process.
Patients and prescribers must now navigate the withdrawal process. The FDA is advising those currently on Ocaliva to consult healthcare professionals before making any changes to their treatment.
Transition plans may include alternative therapies, and coverage or insurance may be affected. Intercept’s “withdrawal FAQ” clarifies that this is not a recall in the usual sense but a regulatory withdrawal requested by the FDA.
The FDA will monitor any safety signals closely during the transition, and additional data from Intercept’s earlier trials, real-world evidence, and long-term patient registries may be re-examined.
Intercept has argued these data support Ocaliva’s benefit-risk profile, but the FDA believes the risks—particularly serious liver injury—cannot be sufficiently mitigated across the indicated patient population.
