The FDA has denied full approval for Intercept Pharmaceuticals' obeticholic acid (Ocaliva) for the treatment of primary biliary cholangitis (PBC), issuing a Complete Response Letter (CRL) to the company. This decision follows a negative recommendation from the Gastrointestinal Drugs Advisory Committee in September 2024, which questioned the verification of obeticholic acid’s benefit on clinical outcomes and its overall benefit-risk profile.
The advisory committee voted 13 to 1 against the verification of Ocaliva's clinical benefit based on data from the postmarketing confirmatory trial 747-302 and observational study 747-405. Additionally, a vote of 10 to 1, with 3 abstentions, indicated that the committee did not find a favorable benefit-risk assessment for Ocaliva as a second-line treatment in the indicated population.
The CRL, issued on November 12, 2024, also indicated that the FDA is continuing to evaluate safety data from Study 747-302, alongside other safety information. Intercept Pharmaceuticals maintains that Ocaliva's safety profile is supported by extensive data from long-term clinical trials, real-world evidence, and post-marketing experience spanning 42,000 patient-years.
"We believe in the totality of evidence supporting OCALIVA and intend to work closely with the FDA on next steps," stated Vivek Devaraj, US President and Chairman at Intercept. "We remain committed to patients living with PBC who have limited treatment options."
Despite the denial of full approval, obeticholic acid remains available for appropriate PBC patients in the US under accelerated approval status. Previously, Ocaliva was the only second-line therapy available for PBC patients who did not respond to or could not tolerate ursodeoxycholic acid (UDCA). However, in 2024, the FDA granted accelerated approvals to elafibranor (Iqirvo) and seladelpar (Livdelzi), providing additional second-line treatment options for PBC patients.
