Intercept announces FDA acceptance of supplemental NDA for Ocaliva (obeticholic acid) for the treatment of primary biliary cholangitis (PBC)

Intercept Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) for Ocaliva (a farnesoid X receptor (FXR) agonist) for the treatment of individuals with primary biliary cholangitis (PBC). This sNDA for Ocaliva is intended to satisfy the post-marketing requirements to confirm a clinical benefit in patients with PBC. 

The FDA has assigned a PDUFA target action date of October 15, 2024.

In this communication, FDA informed Intercept that they are planning to hold an Advisory Committee meeting to discuss the application. 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 US claims database and international PBC patient registries. 

Approval is uncertain, as the outcomes study was unable to show benefit and it is unclear how the FDA will weigh real-world evidence data. The proceeding/decision will set an important precedent for guiding future postmarketing commitments and full approval in the PBC market. A negative decision would initiate proceedings to remove OCA from the market

In COBALT RCT, 21/81 (25.9%) OCA-treated and 19/68 (27.9%) placebo subjects experienced a composite event (HR, 0.88; 95% CI, 0.47–1.65). In the COBALT as-treated external control (EC) analysis, 10/81 (12.4%) OCA-treated patients and 18/74 (24.6%) non–OCA-treated weighted controls experienced an event (HR, 0.36; 95% CI, 0.16–0.79). Among patients consistent with the current USPI, a composite endpoint of death, liver transplant, and progression to hepatic decompensation and/or PH was less frequent for OCA-treated patients. Despite substantial treatment crossover and informative censoring, the COBALT RCT showed a non-statistically significant efficacy signal in favor of OCA treatment, and both the COBALT EC and HEROES trial emulation studies showed statistically significant superiority of OCA vs non-treatment (Source- see Abstract 116). Study -401, was reported as terminated by Intercept on August 5, 2021 reportedly due to Ocaliva (obeticholic acid) US labeling update (letter)

Ocaliva received accelerated approval in 2016 and is indicated for the treatment of adult patients living with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, either in combination with ursodeoxycholic acid (UDCA) with an inadequate response to UDCA or as monotherapy in patients unable to tolerate UDCA. The accelerated approval was based on a reduction in alkaline phosphatase (ALP). An improvement in survival or disease-related symptoms has not been established yet. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

About Primary Biliary Cholangitis
Primary biliary cholangitis (PBC) is a rare, progressive, and chronic autoimmune disease that affects the bile ducts in the liver and is most prevalent (approximately 1 in 10,000) in women over the age of 40. PBC causes bile acid to build up in the liver, resulting in inflammation and scarring (fibrosis), which, if left untreated, can lead to cirrhosis, a liver transplant, or death.

Intercept Pharmaceuticals, Inc. is a biopharmaceutical company and wholly owned subsidiary of Alfasigma S.p.A.

Source: Press Release