Ocaliva (obeticholic acid) by Intercept Pharmaceuticals: Drug Safety Communication - Serious Liver Injury Being Observed in Patients without Cirrhosis

The FDA identified cases of serious liver injury among patients being treated for primary biliary cholangitis (PBC) with Ocaliva (obeticholic acid) who did not have cirrhosis of the liver. 

The original clinical trial showed a decrease in alkaline phosphatase (ALP) that supported FDA accelerated approval. FDA required the additional postmarket clinical trial to verify the clinical benefit of Ocaliva. FDA evaluated liver safety in the postmarket clinical trial in patients who were appropriate for Ocaliva treatment based on the approved indication in the prescribing information. Among these patients, the risk of both liver transplant and death were higher in patients receiving Ocaliva compared with those receiving placebo. Specifically, among patients for whom Ocaliva was indicated, which were those with a lower risk of progression to liver transplant or death, 7 of 81 who received Ocaliva needed a liver transplant compared to 1 of 68 patients who received placebo. (Note: The liver transplant case in the placebo group occurred after the patient switched to commercially available Ocaliva and was dosed with Ocaliva for two years prior to liver transplant; this case may also be related to Ocaliva treatment.) An additional four patients receiving Ocaliva died, compared to one receiving placebo. Analyses evaluating the risk of liver transplant and death resulted in a hazard ratio of 4.77 (95% confidence interval: 1.03, 22.09) for patients without advanced cirrhosis and not contraindicated from receiving the drug.

FDA is notifying health care professionals and patients of this new safety information, and that frequent liver test monitoring is necessary to identify worsening liver function and ensure appropriate discontinuation of Ocaliva. FDA will continue to monitor the medicine’s safety and will follow up if additional information becomes available.