FDA approves Ocaliva for primary biliary cholangitis

The US Food and Drug Administration (FDA) has granted accelerated approval to Intercept Pharmaceuticals’ Ocaliva (obeticholic acid) for the treatment of primary biliary cholangitis, previously known as primary biliary cirrhosis (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 an agonist of the farnesoid X receptor (FXR), a nuclear receptor expressed in the liver and intestine and a key regulator of bile acid, inflammatory, fibrotic and metabolic pathways.

Commenting on the news, Mark Pruzanski, M.D., Chief Executive Officer and President of Intercept, said: “We are very pleased that the FDA has approved Ocaliva for PBC and would like to thank all the patients and investigators around the world who participated in our clinical trials to make this possible.”

“Ocaliva fills an important unmet need for the many patients with PBC who have an inadequate response to or are intolerant of UDCA, which until now has been the only approved treatment,” said John Vierling, M.D., F.A.C.P., F.A.A.S.L.D., Professor of Medicine and Surgery at Baylor College of Medicine and Past President of the American Association for the Study of Liver Diseases (AASLD). “Ocaliva has demonstrated a clinically meaningful improvement in lowering ALP, a liver enzyme and biomarker that is used to track disease progression in patients with PBC. Importantly, Ocaliva maintained durable ALP reductions, which is critical for treatment of a chronic disease like PBC.”

Approval based on a reduction in ALP

The FDA’s approval is based on a reduction in the level of the biomarker alkaline phosphatase (ALP), as a surrogate endpoint which, based on multiple levels of evidence (mechanistic, clinical trial, epidemiologic), could be relied upon to be reasonably likely to predict clinical benefit, including an improvement in transplant free-survival. The safety and efficacy of Ocaliva were demonstrated in a controlled clinical trial with 216 participants. After twelve months, the proportion of participants achieving reductions in ALP levels was higher among Ocaliva-treated participants compared to placebo-treated participants.

The most common side effects of Ocaliva are severe itching of the skin (pruritus), fatigue, abdominal pain and discomfort, joint pain (arthralgia), pain in the middle part of the throat (oropharyngeal), dizziness and constipation.