Intercept Pharmaceuticals Inc, a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat progressive non-viral liver diseases, announced that the European Commission has granted conditional approval for Ocaliva (obeticholic acid) for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA. Ocaliva is a potent and selective agonist of the farnesoid X receptor (FXR), which is expressed at high levels in the liver and intestine and thought to be a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways.

"The approval of Ocaliva in Europe provides a new therapeutic option for a substantial group of PBC patients who are not achieving treatment goals with UDCA alone or who cannot tolerate UDCA," said Frederik Nevens, University Hospitals Leuven & KU Leuven, Belgium, and the lead investigator of the Phase 3 POISE clinical study. "Despite the availability of UDCA, many patients have remained at significant risk of adverse outcomes with no alternative treatment option available. Ocaliva can now help fill an important unmet need for these patients."

"We are delighted to be introducing the first new therapeutic option for PBC in nearly 20 years in Europe where this disease is a major reason for liver failure and a leading cause of liver transplant in women," said Lisa Bright, Intercept's President, International. "Following approval in the U.S. earlier this year, Ocaliva's marketing authorization in Europe represents another big step in Intercept's mission to provide patients with worldwide access to our innovative therapy. This great achievement will motivate us further to continue developing solutions that improve the lives of people with progressive non-viral liver diseases."

The marketing authorization allows Intercept to market Ocaliva in 28 countries that are member states of the European Union, as well as 3 additional European Economic Area member states. As conditions of the approval, Intercept is required to provide post-approval updates on safety and efficacy analyses for Ocaliva from the ongoing Phase 4 COBALT outcomes study and a short-term study in patients with hepatic impairment.

"As a community, our priority is to advocate for changes which ensure that people diagnosed with PBC have the best possible prognosis," said Tatjana Reic, President of the European Liver Patients Association (ELPA). "With this in mind, we are excited about this advance for patients with an inadequate response or intolerability to the current available treatment. Such patients will soon have access to a new treatment option to manage their PBC."

The marketing authorization was based on efficacy and safety data derived from three randomized double-blind, placebo-controlled clinical trials evaluating the effect of Ocaliva on alkaline phosphatase (ALP) and bilirubin in patients with PBC. It was also supported by two clinical databases that include more than 10,000 patients from the Global PBC Study Group and UK-PBC Group, both independently confirming that achieving lower ALP and/or bilirubin levels is significantly correlated with increased transplant-free survival.

In the Phase 3 POISE study, nearly half of patients (46%) in the titration group treated with Ocaliva in combination with UDCA achieved the primary endpoint compared to 10% in the control group (placebo added to UDCA) (p<0.0001). Additionally, 77% of patients taking Ocaliva in combination with UDCA achieved a reduction of more than 15% in ALP at 12 months, compared to 29% taking UDCA alone.

The most commonly reported adverse reactions were pruritus (63%) and fatigue (22%). Adverse reactions leading to discontinuation were 1% in the Ocaliva titration arm and 11% in the Ocaliva 10 mg arm. The most common adverse reaction leading to discontinuation was pruritus. The majority of pruritus occurred within the first month of treatment and tended to resolve over time with continued dosing.