Intercept Pharma to initiate Phase III trial of OCA for NASH.

Intercept Pharmaceuticals, Inc. announced its plans for an international Phase III trial of obeticholic acid (OCA), the company's lead FXR agonist, in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with liver fibrosis. OCA has received breakthrough therapy designation in this patient population from the FDA. In accordance with harmonized advice from the FDA and European Medicines Authority (EMA), the Randomized Global Phase III Trial to Evaluate the Impact on NASH with Fibrosis of Obeticholic Acid Treatment (REGENERATE) has been designed as a double-blind, placebo-controlled pivotal Phase III clinical trial expected to enroll up to approximately 2,500 patients and assess the potential benefit of OCA treatment on liver-related clinical outcomes.

The trial will include a pre-planned interim histology analysis after 72 weeks of treatment in approximately 1,400 patients which is intended to serve as the basis for seeking U.S. and international marketing approvals of OCA for the treatment of NASH patients with liver fibrosis. The REGENERATE trial will be conducted at approximately 250 centers in North America, Europe and other regions and trial initiation is anticipated in 3Q 2015. Patients will be randomized 1:1:1 to one of placebo, 10 mg of OCA, or 25 mg of OCA, taken once daily. The study population will primarily be comprised of NASH patients with stage 2 or stage 3 advanced liver fibrosis who will be evaluated on the primary efficacy endpoints in the 72-week interim analysis and subsequently. In addition, a relatively small group of NASH patients with stage 1 early liver fibrosis with an increased risk of rapid progression due to concomitant diabetes, obesity or active liver inflammation indicated by elevated ALT will also be enrolled, but not included in the primary endpoint analyses.

Comment: The Phase III REGENERATE trial of OCA will have dual endpoints in liver fibrosis with no worsening NASH and the resolution of NASH with no worsening of liver fibrosis.The potential to reverse liver fibrosis (identified in the FLINT study) may put OCA in the lead of the seven drug competitors for the NASH market.