FDA approves rare liver disease drug

June 27, 2016

FDA recently granted accelerated approval for obeticholic acid (Ocaliva, Intercept Pharmaceuticals, Inc.) for the treatment of primary biliary cholangitis.

FDA recently granted accelerated approval for obeticholic acid (Ocaliva, Intercept Pharmaceuticals, Inc.) for the treatment of primary biliary cholangitis.

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a rare and chronic liver disease that results from autoimmune destruction of the bile ducts that transport bile acids out of the liver. When left untreated, PBC can progress to hepatic fibrosis, cirrhosis, liver failure and death unless the patient receives a liver transplant. 

Ocaliva is already available through specialty pharmacy networks.

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UDCA, the only other approved treatment for PBC, was approved by FDA in 1997. It is effective in more than 50% of patients, but up to 40% of patients do not achieve an adequate reduction in blood chemistries with the medication, while 5% to 10% are 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. Ocaliva increases bile flow from the liver and suppresses bile acid production in the liver, thus reducing the exposure of the liver to toxic levels of bile acids.

Ocaliva is approved for the treatment of PBC in combination with ursodeoxycholic acid in adults with an inadequate response to UDCA, or as single therapy in adults unable to tolerate UDCA. This indication granted under accelerated approval based on a reduction in alkaline phosphatase; an improvement in survival, progression to cirrhosis, or disease-related symptoms has not been established.

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"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, MD, 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."

FDA’s approval was based on the phase 3 POISE trial, which studied the safety and efficacy of once-daily Ocaliva versus placebo in PBC patients with an inadequate response to, or who are unable to tolerate, UDCA. The primary endpoint in the study was the reduction in serum alkaline phosphatase (ALP) to below a threshold of 1.67 times the upper limit of normal.

After 12 months, the proportion of participants achieving reductions in ALP levels was higher among Ocaliva-treated participants compared to placebo-treated participants.

Some of the most common adverse reactions associated with the use of Ocaliva include pruritus, fatigue, abdominal pain and discomfort, and arthralgia. 

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