FDA Extends Review of Obeticholic Acid (Ocaliva) sNDA for Primary Biliary Cholangitis

Vivek Devaraj

Credit: Intercept

Intercept Pharmaceuticals has announced the US Food and Drug Administration has extended its review of the supplemental New Drug Application (sNDA) for full approval of obeticholic acid (Ocaliva) for the treatment of primary biliary cholangitis (PBC).¹

According to a press release from Intercept, its action under the Prescription Drug User Fee Act (PDUFA), which was expected on October 15, 2024, has been delayed, and the FDA has not provided a new anticipated action date. Of note, obeticholic acid is still available for the treatment of appropriate PBC patients in the US under accelerated approval status.¹

“We will continue to engage with the FDA regarding our pending application,” Vivek Devaraj, US president and chairman at Intercept, said in a press release.¹ “We are grateful for the continuous and ongoing support of the PBC community.”

The announcement of the extended sNDA review comes weeks after a US Food and Drug Administration Gastrointestinal Drug Advisory Committee meeting yielded a negative opinion on the verification of obeticholic acid’s benefit on clinical outcomes in PBC as well as its benefit versus risk profile. Specifically, the advisory committee voted 13 to 1 with no abstentions that the benefits of obeticholic acid on clinical outcomes in patients with PBC could not be verified with available data from the postmarketing requirement confirmatory trial 747-302 and the observational study 747-405. The committee also voted 10 to 1, with 3 abstentions, that obeticholic acid did not have a favorable benefit-risk assessment for use as a second-line treatment in the United Stated Prescribing Information population.^1,2

As a farnesoid X receptor (FXR) agonist, obeticholic acid increases bile flow from the liver and suppresses bile acid production in the liver, reducing hepatic exposure to toxic levels of bile acids. It was granted accelerated approval for the treatment of PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as a single therapy in adults unable to tolerate UDCA on May 31, 2016, based on a reduction in the biomarker alkaline phosphatase (ALP). Obeticholic acid’s accelerated approval made it the second approved treatment for PBC, the first being UDCA nearly 20 years prior.³

For many years, obeticholic acid was the sole second-line therapy in PBC and was the only option for patients who did not respond to or could not tolerate UDCA. In 2024, over the span of 2 months, the FDA granted accelerated approvals to both elafibranor (Iqirvo) and seladelpar (Livdelzi), making them the second and third approved second-line therapies in PBC, respectively.^4,5

In the absence of an action from the FDA, obeticholic acid remains available for the treatment of PBC in the US under its previous accelerated approval status.¹

References

1. ^{Intercept Pharmaceuticals. Intercept Provides Regulatory Update Regarding sNDA for OCALIVA. October 17, 2024. Accessed October 17, 2024. https://www.interceptpharma.com/about-us/news/?id=2964897}
2. ^{Brooks, A. Nancy Reau, MD: Obeticholic Acid’s Future in PBC After FDA Advisory Committee Meeting. HCPLive. September 20, 2024. Accessed October 14, 2024. https://www.hcplive.com/view/nancy-reau-md-obeticholic-acid-future-pbc-fda-advisory-committee-meeting}
3. ^{FDA. FDA approves Ocaliva for rare, chronic liver disease. FDA Newsroom. May 31, 2016. Accessed October 14, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-ocaliva-rare-chronic-liver-disease}
4. ^{Brooks, A. FDA Grants Accelerated Approval to Elafibranor (Iqirvo) for PBC. HCPLive. June 10, 2024. Accessed October 15, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-elafibranor-iqirvo-for-pbc}
5. ^{Brooks, A. FDA Grants Accelerated Approval to Seladelpar (Livdelzi) for Primary Biliary Cholangitis. HCPLive. August 14, 2024. Accessed October 15, 2024. https://www.hcplive.com/view/fda-grants-accelerated-approval-to-seladelpar-livdelzi-for-primary-biliary-cholangitis}