Intercept Pharmaceuticals Withdraws Liver Drug Ocaliva from US Market Amid Regulatory Challenges

Intercept Pharmaceuticals has announced the withdrawal of its liver disease drug Ocaliva (obeticholic acid) from the US market, marking the end of a tumultuous journey for the once-promising treatment. The decision comes in response to a request from the US Food and Drug Administration (FDA), which has also placed a clinical hold on trials of obeticholic acid conducted under US investigational new drug applications.

FDA Concerns and Regulatory Setbacks

Ocaliva, which received accelerated approval in 2016 for the treatment of primary biliary cholangitis (PBC), has faced mounting scrutiny from regulators. In September 2024, FDA staffers raised significant safety concerns, noting unfavorable trends in death and liver transplantation rates among patients treated with the drug. These findings were presented to the FDA's Gastrointestinal Drug Advisory Committee, which subsequently voted against Ocaliva, citing its inability to verify a favorable risk-benefit profile in confirmatory studies.

The FDA's decision to refuse full approval for Ocaliva in November 2024 was followed by further revelations in December. The agency reported instances of serious liver injury in patients treated with Ocaliva and indicated that the drug appeared to worsen the risk of death or need for liver transplantation in its intended patient population.

Impact on Intercept and Future Prospects

Vivek Devaraj, Intercept's US president, expressed the company's continued belief in Ocaliva's safety and efficacy but acknowledged the need to comply with the FDA's request. "While our view of Ocaliva's benefit-risk profile differs from FDA's, we respect its request and have made this difficult decision to provide clear guidance for patients and prescribers," Devaraj stated.

The withdrawal of Ocaliva from the US market represents a significant setback for Intercept, which had previously faced rejections in its attempts to expand the drug's indications to include metabolic dysfunction-associated steatohepatitis (MASH). These failures led to substantial restructuring within the company, including a workforce reduction of one-third and the winding down of MASH-related investments.

In September 2023, Intercept agreed to be acquired by Italian pharmaceutical company Alfasigma for $800 million. At the time, Ocaliva was Intercept's sole product, generating $285.7 million in full-year 2022 sales. The company's pipeline now primarily consists of obeticholic acid formulations, with one other next-generation FXR agonist in early-stage testing for severe alcohol-associated hepatitis.