FDA Rejects Full Approval for Intercept's Ocaliva in Primary Biliary Cholangitis
核心洞察
The FDA issued a complete response letter for Intercept's Ocaliva, preventing its full approval for primary biliary cholangitis (搜索) (PBC).
The decision aligns with a negative opinion from the Gastrointestinal Drugs Advisory Committee (GIDAC) regarding Ocaliva's clinical benefit.
Ocaliva will remain available in the US under its existing accelerated approval, while the FDA considers post-marketing study data.
Intercept Pharmaceuticals has faced a setback as the FDA has decided against granting full approval for Ocaliva (obeticholic acid) in the treatment of primary biliary cholangitis (搜索) (PBC). This decision follows an unfavorable opinion from the FDA's Gastrointestinal Drugs Advisory Committee (GIDAC) in September.
The FDA's complete response letter indicates that Intercept's application to convert Ocaliva's accelerated approval to full approval has been unsuccessful. Despite this, Ocaliva will continue to be available for PBC patients in the US under the accelerated approval granted in 2016, according to a press release issued on November 12.
The agency stated that it was "unable to approve the supplemental new drug application (sNDA) in its current form," mirroring the sentiment expressed during the GIDAC meeting in September 2024. During that meeting, 13 panel members expressed doubts that Intercept's data sufficiently demonstrated Ocaliva's clinical benefit, with only one panelist voting in favor. In a separate vote, 10 experts concluded that the drug's benefits did not outweigh its risks, while one panelist believed the benefits outweighed the risks, and three abstained. The FDA's letter to Intercept also indicated ongoing consideration of data from the post-marketing study 747-302 (NCT02308111), in addition to other safety information. Ocaliva carries a boxed warning regarding the heightened risk of liver decompensation or failure if patients are dosed incorrectly.
Intercept's US president, Vivek Devaraj, stated, "We believe in the totality of evidence supporting Ocaliva and intend to work closely with the FDA on next steps."
Regulatory Challenges and Market Context
Ocaliva has encountered regulatory hurdles in both the US and Europe. In June of the previous year, the FDA rejected Ocaliva's use in nonalcoholic steatohepatitis (NASH (搜索)), leading Intercept to reduce its workforce by a third. Furthermore, the FDA delayed its decision on full approval for PBC, pushing back the Prescription Drug User Fee Act (PDUFA) date originally set for October 15.
In the same month as the negative AdCom meeting, the European Commission (EC) withdrew Ocaliva's conditional marketing authorization as a second-line treatment for PBC patients. This decision followed a reassessment of the drug's benefit-risk profile by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use. However, the President of the General Court of the European Union overruled the decision, allowing Ocaliva to remain on the market.
PBC Treatment Landscape
Primary biliary cholangitis (搜索) (PBC) is a liver disease characterized by inflamed bile ducts that are progressively destroyed due to bile buildup, disproportionately affecting women. Ocaliva targets the farnesoid X receptor (搜索) (FXR) to reduce bile acid production and promote its removal.
The scrutiny of Ocaliva coincides with the recent FDA accelerated approval of Gilead's Livdelzi (seladelpar) for PBC in August, a drug acquired from CymaBay Therapeutics (搜索) in a $4.3 billion deal. GlobalData’s Pharma Intelligence Centre forecasts Livdelzi to generate $558 million in 2030.
Intercept now operates as a subsidiary of Italy-based Alfasigma, following a $794 million acquisition in September 2023. Prior to this acquisition, Ocaliva generated $285.7 million in 2022.