The Food and Drug Administration (FDA) has uncovered additional safety concerns related to a medication used to treat a rare liver disease, casting further doubt on the prospects of a drug once considered a potential blockbuster.
On Thursday, the FDA announced findings of severe liver impairment in patients treated with Ocaliva, a drug used to manage primary biliary cholangitis (PBC), a rare autoimmune liver disease. The rights to Ocaliva in the U.S. are currently held by the Italian pharmaceutical company Alfasigma.
These concerns emerged from a review of clinical trial data conducted after the drug’s initial approval. Notably, the adverse events occurred in patients who did not yet have cirrhosis, a severe form of liver scarring. This is particularly concerning, as the FDA had already restricted Ocaliva’s use in 2021 for patients with advanced cirrhosis due to safety risks.
Since those restrictions were implemented, the FDA has recorded 20 additional cases involving liver transplants, patients placed on liver transplant lists, or fatalities linked to liver issues in individuals treated with Ocaliva. The agency has emphasized the importance of regular liver function monitoring to facilitate timely discontinuation of the drug and early detection of declining organ function in patients undergoing treatment.
The FDA has urged healthcare providers to discontinue Ocaliva in cases where the patient’s condition worsens or the drug proves ineffective. The agency will continue to monitor Ocaliva’s safety profile and evaluate new information as it becomes available.
This latest development is another setback for Ocaliva, a drug that was once among the most closely watched in the biotechnology sector.
Obeticholic acid, marketed as Ocaliva, was originally developed by Intercept Pharmaceuticals and received FDA approval in 2016 as the first new treatment for PBC in two decades. Intercept initially had high hopes for the drug, aiming to expand its use as the first treatment for metabolic dysfunction-associated steatohepatitis (MASH), a much more prevalent liver disease and a leading cause of liver transplants.
Early clinical results for Ocaliva led to a surge in Intercept’s valuation and generated significant excitement around MASH as a lucrative market for pharmaceutical innovation. However, subsequent studies raised doubts about the drug’s efficacy while highlighting safety risks, including drug-induced liver damage. The FDA denied Ocaliva’s applications for MASH approval twice, in 2020 and 2023, forcing Intercept to scale back its operations, cut jobs, and ultimately halt further research on the drug. Following the second rejection, Intercept sold the rights to Ocaliva to Alfasigma.
The drug’s struggles have continued globally. Earlier this year, European regulators revoked Ocaliva’s marketing authorization in the EU, where Advanz Pharma held its rights under a 2022 agreement with Intercept. In the U.S., the FDA declined to convert Ocaliva’s 2016 accelerated approval for PBC into full approval but allowed the drug to remain on the market under its original license.
