Intercept Pharmaceuticals, Inc., a biopharmaceutical company focused on the development and commercialization of novel therapeutics to treat non-viral, progressive liver diseases, announced the filing of a New Drug Submission to Health Canada, seeking Canadian marketing approval for obeticholic acid (OCA) for the treatment of primary biliary cholangitis, also referred to as primary biliary cirrhosis (PBC), when used in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA or as monotherapy in adults unable to tolerate UDCA.

"Our submission to Health Canada not only reflects a significant milestone for Intercept, but more importantly for the estimated 8,000 Canadians living with PBC, many of whom remain at risk of liver failure and need for transplantation despite the current standard of care," said Dr. Mark Pruzanski, president & CEO of Intercept Pharmaceuticals. "We are pleased with Health Canada's decision to grant OCA priority review status, recognizing the high unmet medical need for new therapies in PBC and the potential of OCA to offer meaningful benefits in improving outcomes for patients impacted by the disease."

PBC is a rare, autoimmune cholestatic liver disease that puts patients at risk for life-threatening complications. It is primarily a disease of women, affecting approximately one in 1,000 women over the age of 40. If left untreated, survival of patients with PBC is significantly worse than that of the general population.

Canadian researchers have played a significant role in advancing the clinical research and management of PBC. With seven clinical trial sites across the country participating in the OCA PBC clinical development program, Canadian clinicians, patients and health institutions have made a meaningful contribution to the development of OCA.

"Both patients and doctors have been looking forward to new avenues of treatment for PBC patients at risk of disease progression. We have made great inroads in understanding what may cause PBC but this has not really impacted patient care - for a rare disease there are too many patients with PBC waiting for liver transplantation," said Dr. Andrew Mason, Director of Research for the Division of Gastroenterology and Hepatology at the University of Alberta. "In clinical trials, OCA made a significant and clinically meaningful impact on lab tests used to monitor biliary disease, such as alkaline phosphatase and bilirubin.  We are hopeful that OCA will be available soon for our patients with PBC."

Obeticholic acid is an agonist of the farnesoid X receptor (FXR), a nuclear receptor expressed in the liver and intestine.

The Canadian New Drug Submission includes a total of 1,507 subjects exposed to at least a single dose of obeticholic acid. Of these subjects, 432 were patients with PBC, with 290 treated for at least six months and 232 treated for at least one year. The key efficacy and safety data are derived from three randomized double-blind, placebo-controlled clinical trials in patients with PBC evaluating the effect of obeticholic acid on alkaline phosphatase (ALP) and bilirubin. All three trials met their primary endpoints with high statistical significance and improvements were seen in secondary endpoints including markers of liver injury, immunity, inflammation and apoptosis. Pruritus (itching), a common symptom of PBC that is unrelated to disease stage or outcomes, was the most common side effect observed in obeticholic acid-treated patients.

The regulatory submission is 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 Canada, obeticholic acid is an investigational agent and has not been approved by Health Canada. In May 2016, the US Food and Drug Administration (FDA) granted accelerated approval to obeticholic acid for the treatment of PBC under the brand name Ocaliva based on a reduction in ALP. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. A marketing authorization application for obeticholic acid for the treatment of PBC was accepted by the European Medicines Authority (EMA) in June 2015 and is currently under review. The brand name Ocaliva has been provisionally approved by the EMA.

The most common adverse reactions from subjects taking Ocaliva (=5%) were pruritus, fatigue, abdominal pain and discomfort, rash, oropharyngeal pain, dizziness, constipation, arthralgia, thyroid function abnormality and eczema.