FDA Sets Date for Full Approval of Ocaliva in Liver Disease

The FDA has accepted the supplemental new drug application (sNDA) for Ocaliva (obeticholic acid) to treat patients with primary biliary cholangitis (PBC). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of Oct. 15, 2024. The plans to hold an advisory committee meeting to discuss the application.

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.

Ocaliva was deveolped by Intercept Pharmaceuticals, which was acquired by Alfasigma in November 2023. Ocaliva is a farnesoid X receptor (FXR) agonist that received accelerated approval in 2016. It is indicated for adult patients living with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis. The sNDA is supported by data from the company’s post-marketing requirement studies COBALT and Study 401 as well as real-world evidence from a U.S. claims database and international PBC patient registries.

Ocaliva has a price of $9,509 for a supply of 30 tablets, according to Drugs.com. Intercept provides $0 copay assistance for eligible commercially insured patients, up to a maximum of $10,000 per year.

Related: FDA Rejects NDA for Fatty Liver Disease Therapy

Intercept had been studying obeticholic acid to treat patients with pre-cirrhotic fibrosis due to nonalcoholic steatohepatitis (NASH). NASH is a progressive liver disease caused by excessive fat accumulation in the liver that leads to inflammation and liver injury.

But the company discontinued the program after the FDA issued a complete response letter (CRL) in June for this indication. This decision came after an FDA advisory committee voted no on the question of whether the efficacy and safety of obeticholic acid outweigh the risks. In its CRL, the FDA indicated that any resubmission of an NDA for OCA in NASH would require data on long-term outcomes.

This was the second complete response letter for obeticholic acid for use in NASH. Intercept had resubmitted an NDA in December 2022, after the FDA issued CRL in June 2020. At issue was Intercept’s use of a surrogate endpoint. The agency wanted to see additional post-interim analysis efficacy and safety data.

Since then, Intercept’s research has been focused on a fixed-dose combination of obeticholic acid and the lipid-lowering drug bezafibrate to treat patients with primary biliary cholangitis. In November 2023, the company announced results from two phase 2 studies showing the combination achieved improvement on key serum biomarkers in 40% to 44% of patients in the first 12 weeks. These data were presented at the American Association for the Study of Liver Diseases’ meeting in November 2023.