The Food and Drug Administration (FDA) has accepted the resubmitted New Drug Application (NDA) for obeticholic acid (OCA) for the treatment of patients with pre-cirrhotic liver fibrosis due to nonalcoholic steatohepatitis (NASH).
The NDA is supported by 2 interim analyses from the double-blind, placebo-controlled phase 3 REGENERATE trial (ClinicalTrials.gov Identifier: NCT02548351), which included patients with biopsy-proven stage 2 or 3 liver fibrosis due to NASH. Participants were randomly assigned 1:1:1 to receive OCA 10mg (n=312), OCA 25mg (n=308), or placebo (n=311) orally once daily for 18 months. The coprimary endpoints were the proportion of patients achieving at least 1 stage of liver fibrosis improvement with no worsening of NASH; or the proportion of patients achieving NASH resolution with no worsening of liver fibrosis.
Findings from the most recent analysis of the intent-to-treat population showed that 22.4% of patients treated with OCA 25mg met the primary endpoint achieving at least 1 stage of fibrosis improvement with no worsening of NASH at month 18 on liver biopsy compared with 9.6% of patients treated with placebo (P <.0001). These findings were consistent with the original positive analysis announced in February 2019, which also showed that OCA 25mg led to fibrosis improvement by at least 1 stage with no worsening of NASH at 18 months (P =.0002).
The most common treatment-emergent adverse event reported was pruritus. The OCA 25mg group was observed to have higher rates of biliary events, including gallstones. An analysis of safety data through 4 years showed a numerically higher number of adjudicated hepatic safety events for OCA 25mg, most of which were mild in severity.
“This regulatory milestone brings us one step closer to reaching our goal of delivering the first available therapy for patients living with pre-cirrhotic fibrosis due to NASH – the most rapidly growing cause of liver transplantation in the US,” said Jerry Durso, President and CEO of Intercept. “We believe OCA has the potential to become an important therapy given its strong and direct antifibrotic effect, and we look forward to continuing our work with FDA over the coming months as they review our NDA.”
The application has been assigned a Prescription Drug User Fee Act target date of June 22, 2023.
OCA is currently approved under the brand name Ocaliva for the treatment of adult patients with primary biliary cholangitis 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.
- FDA accepts Intercept’s New Drug Application for OCA for the treatment of pre-cirrhotic liver fibrosis due to NASH. News release. Intercept Pharmaceuticals, Inc. Accessed January 19, 2023. https://www.globenewswire.com/news-release/2023/01/19/2591748/23024/en/FDA-Accepts-Intercept-s-New-Drug-Application-for-OCA-for-the-Treatment-of-Pre-Cirrhotic-Liver-Fibrosis-Due-to-NASH.html.
- Intercept announces positive data in fibrosis due to NASH from a new analysis of its phase 3 REGENERATE study of obeticholic acid (OCA). News release. July 7, 2022. Intercept Pharmaceuticals, Inc. Accessed January 19, 2023. https://ir.interceptpharma.com/news-releases/news-release-details/intercept-announces-positive-data-fibrosis-due-nash-new-analysis.