Intercept Withdraws Ocaliva from Market After FDA Raises Safety Concerns

Intercept Pharmaceuticals has voluntarily withdrawn Ocaliva (obeticholic acid) from the U.S. market. Ocaliva is approved to treat patients with primary biliary cholangitis (PBC), a rare, progressive liver disease.

PBC is a progressive autoimmune disease that results from the destruction of the bile ducts in the liver. This leads to inflammation, scarring, and cirrhosis. The disease affects mostly women.

This decision follows a request from the FDA. In addition, the FDA has placed a clinical hold on all Intercept clinical trials involving obeticholic acid. Regulators said they had identified cases of serious liver injury among some trial participants who did not have a history of cirrhosis.

Vivek Devaraj

“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,” Vivek Devaraj, U.S. president at Intercept, said in a news release.

Ocaliva was developed by Intercept, which was acquired by Alfasigma in November 2023. Ocaliva is a farnesoid X receptor (FXR) agonist that received accelerated approval in 2016. But the FDA had a complete response letter (CRL) in November 2024, after an advisory committee meeting voted 10 to 1 against Ocaliva, saying that the benefit-risk profile is not supported. At that time, the FDA indicated that it was continuing to study the safety data from Study 747-302.

The FDA then issued a drug safety communication for providers to monitor liver tests for patients being treated with Ocaliva. An FDA review of clinical trial data from Study 747-302 submitted by Intercept as part of a supplemental new drug application (sNDA) seeking full approval for primary biliary cholangitis.

In January 2025, FDA officials issued a safety warning about serious liver injury in patients taking Ocaliva. Additionally, a review of postmarket clinical trial data identified cases of liver-related events among patients taking Ocaliva, with some requiring a liver transplant. In the postmarket trial, the risk of both liver transplant and death was higher in patients receiving Ocaliva compared with those receiving placebo.

Specifically, among patients for whom Ocaliva was indicated, 7 of 81 who received Ocaliva needed a liver transplant compared with 1 of 68 patients who received a placebo. An additional 4 patients receiving Ocaliva died, compared with 1 receiving placebo.

In 2021, regulators had updated the prescribing information and restricted its use to patients with PBC with advanced cirrhosis after a review found that patients without cirrhosis experienced liver injury. Following this restriction, regulators identified 20 cases between May 26, 2021, and Sept. 18, 2024, of patients treated with Ocaliva who required liver transplant, evaluation or listing for liver transplant, or liver-related death.

Regulators also found three U.S. cases of liver-related events that occurred in patients for whom Ocaliva should have been discontinued based on the progression of their liver disease.