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

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

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

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

The announcement of the expanded sNDA review comes several weeks after a meeting of the US Food and Drug Administration’s Drug Advisory Committee issued a negative opinion on the validation of obeticholic acid’s benefits in clinical outcomes. on PBC as well as its benefits versus risk profile. In particular, the advisory committee voted 13 to 1 without avoiding that the benefits of obeticholic acid on clinical outcomes in patients with PBC could not be confirmed by the data available from the validation trial of postmarketing requirement 747-302 and observational study 747-405. The committee also voted 10 to 1, with 3 abstentions, that obeticholic acid did not have a good risk assessment for use as a second treatment in the United States 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 the liver’s 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 monotherapy in adults who cannot tolerate UDCA on May 31, 2016, based on biomarker decline. alkaline phosphatase (ALP). Obeticholic acid’s rapid approval made it the second approved treatment for PBC, the first being UDCA nearly 20 years earlier.³

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

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

References

1. ^{Prevent Medicines. Intercept Submits 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: The Future of Obeticholic Acid in PBC After an 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. The 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 Improve Approval of 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}