FDA Accepts Application for NASH Drug

The FDA has accepted Intercept Pharmaceuticals’ resubmission of its new drug application (NDA) for obeticholic acid (OCA) seeking accelerated approval to treat patients with pre-cirrhotic liver fibrosis due to nonalcoholic steatohepatitis (NASH). The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of June 22, 2023.

NASH is a serious progressive liver disease caused by excessive fat accumulation in the liver that induces chronic inflammation, resulting in progressive fibrosis that can lead to cirrhosis, eventual liver failure, cancer and death. Advanced fibrosis is associated with a substantially higher risk of liver-related morbidity and mortality. There are currently no medications approved for the treatment of NASH.

Intercept had resubmitted the NDA in December 2022, following the FDA’s complete response letter that was issued in June 2020. At issue was Intercept’s use of a surrogate endpoint. The agency wanted to see additional post-interim analysis efficacy and safety data from the REGENERATE study.

The new submission contains data from two interim 18-month analyses from the pivotal phase 3 REGENERATE study in patients with pre-cirrhotic liver fibrosis due to NASH. In these analyses, which were announced in July 2022, OCA 25 mg demonstrated double the response rate of placebo in reduction in liver fibrosis stage without worsening of any of the three histologic components of NASH.

Data released in July 2022 of a second interim analysis of the intent-to-treat population from REGENERATE showed that 22.4% of the 931 patients randomized to once-daily oral OCA 25 mg met the primary endpoint of achieving at least one stage of fibrosis improvement with no worsening of NASH.

The new submission also includes safety data from 2,477 patients, including nearly 1,000 patients on study drug for at least four years. Treatment-emergent adverse events (TEAEs), treatment-emergent serious adverse events (TESAEs), and deaths were generally balanced across the OCA and placebo treatment groups. The most common TEAE was pruritus or itchy skin (24% in placebo, 33% in OCA 10 mg, 55% in OCA 25 mg) and pruritus was the most common cause for treatment discontinuation.

Obeticholic acid is currently available with the brand name Ocaliva to treat adult patients with primary biliary cholangitis, which is an inflammation of the bile duct system.