FDA delays approval for Intercept's Ocaliva liver drug

Intercept Pharmaceuticals is experiencing further delays in receiving full approval for its drug Ocaliva (obeticholic acid) from the US Food and Drug Administration (FDA). Initially slated for a decision by October 15, the FDA has requested more time to evaluate the supplemental New Drug Application (sNDA) for the drug, adding to the series of setbacks Ocaliva has faced since its accelerated approval in 2016. The exact new decision date remains unspecified, but Intercept's president, Vivek Devaraj, has indicated the company's commitment to ongoing discussions with the FDA.

Ocaliva, primarily utilized by patients with primary biliary cholangitis (PBC), a rare autoimmune liver disease, was acquired by the Bologna-based company Alfasigma following their $794 million purchase of Intercept Pharmaceuticals in September 2023. Despite operating as a subsidiary under Alfasigma, Ocaliva has encountered several challenges. These include a major 2018 FDA intervention which necessitated a boxed warning due to improper daily dosing of the drug instead of the prescribed weekly regimen.

In September 2024, an FDA advisory committee voted overwhelmingly against granting full approval for Ocaliva. The committee concluded with a 13-1 vote that the drug's clinical benefits were not sufficiently verified through confirmatory evidence. Additionally, in a separate vote, panellists decided 10-1 that the benefits did not outweigh the risks associated with the drug, with three members abstaining.

Moreover, Ocaliva's hurdles extended beyond the US. The European Commission (EC) retracted the drug’s conditional marketing authorization in September 2024, which it had been granted as a second-line treatment for PBC patients. This decision followed a reassessment by the European Medicines Agency’s Committee for Medicinal Products for Human Use, which highlighted concerns over the drug’s benefit-risk profile. However, this decision was unexpectedly overturned within days by the President of the General Court of the European Union, enabling Ocaliva to continue being available on the market.

PBC is a chronic autoimmune disorder that targets the bile ducts in the liver, leading to bile buildup, liver inflammation, and potentially cirrhosis. Ocaliva functions by activating the farnesoid X receptor (FXR) to decrease bile acid production and facilitate its clearance from the liver.

The PBC treatment landscape has become increasingly competitive. In August 2024, the FDA granted accelerated approval to Gilead’s Livdelzi (seladelpar), a drug acquired through a $4.3 billion deal with CymaBay Therapeutics in March 2024. Projections by GlobalData estimate Livdelzi's revenue to reach $558 million by 2030. In comparison, Ocaliva generated $285.7 million in 2022 before being acquired by Alfasigma.

Additionally, in September 2024, the EC approved Ipsen’s Iqirvo (elafibranor) for PBC treatment in conjunction with ursodeoxycholic acid for adults who do not sufficiently respond to ursodeoxycholic acid alone. This European approval follows an earlier accelerated approval by the FDA in June 2024.

These developments signify an evolving and competitive market for PBC treatments, placing Ocaliva and its stakeholders in a waiting game as regulatory bodies continue to deliberate its full approval status.