FDA Clears Obeticholic Acid for Primary Biliary Cholangitis

Megan Brooks


May 31, 2016

The US Food and Drug Administration (FDA) has granted accelerated approval of obeticholic acid (Ocaliva, Intercept Pharmaceuticals, Inc) for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic (UDCA) in adults who fail to respond adequately to UDCA, or as monotherapy in adults who cannot tolerate UDCA.

Last month, the FDA's Gastrointestinal Drugs Advisory Committee voted unanimously for approval, as reported by Medscape Medical News.

Ocaliva is the first new treatment approved for PBC since 1997.

PBC is a rare, chronic, progressive autoimmune disease that puts patients at risk for liver failure and death. Until now, UDCA was the only drug approved to treat PBC, but up 40% of patients fail to respond adequately to UDCA, and 5% to 10% of patients are unable to tolerate it, the FDA notes in a news release.

The approval of obeticholic acid "provides an important treatment option for patients living with PBC who have not responded to the only other approved therapy, UDCA," Amy Egan, MD, deputy director of the Office of Drug Evaluation III in the FDA's Center for Drug Evaluation and Research, said in the release.

Obeticholic acid, given orally, binds to the farnesoid X receptor found in the nucleus of cells in the liver and intestine. "[Farnesoid X receptor] is a key regulator of bile acid 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," the FDA explains.

The POISE Trial

The FDA approval was based on results of the phase 3 POISE trial involving 216 patients who could not tolerate or had not responded adequately to UDCA. All had alkaline phosphatase (ALP) levels at least 1.67 times the upper limit of normal (ULN) and/or total bilirubin levels from the ULN to less than two times the ULN.

Patients were randomly assigned to obeticholic acid 5 mg or 10 mg daily or placebo for 12 months. At 6 months, about half the patients in the 5-mg group who tolerated the drug but still had an ALP level at least 1.67 times the ULN or a bilirubin level below the ULN were titrated to the 10-mg dose.

The primary end point was the proportion of patients achieving an ALP level below 1.67 times the ULN, a decrease in ALP of at least 15% from baseline, and a normal total bilirubin level after 12 months of treatment.

In the intention-to-treat analysis, the primary end point was met by more patients in the 10-mg group than in the placebo group (47% vs 10%; P < .0001), and by more patients in the titration group (46% vs 10%; P < .0001).

The average decrease in ALP level from baseline was better in the 10-mg group than in the placebo group (39% vs 5%; P < .0001) and was better in the titration group (33% vs 5%; P < .0001).

A significant reduction in total bilirubin was also observed in the 10-mg and titration groups (P < .05), whereas there was a tendency toward an increase in the placebo group. There was also a significant decrease in other liver function parameters, including gamma-glutamyl transpeptidase, alanine transaminase, and aspartate aminotransferase (P < .001 for all).

According to the FDA, obeticholic acid has not yet been shown to improve survival, progression to cirrhosis, or other disease-related symptoms, "although a confirmatory trial is currently ongoing."

The most common adverse effects with obeticholic acid are pruritus, fatigue, abdominal pain and discomfort, arthralgia, oropharyngeal pain, dizziness, and constipation. Obeticholic acid should not be used in patients with complete biliary obstruction, the FDA says.

Obeticholic acid, which had fast track and orphan drug designation, was approved under the FDA's accelerated approval program.

Intercept Pharmaceuticals expects obeticholic acid to be available in the United States within 7 to 10 days and said it will be distributed through a specialty pharmacy network.

To help ensure appropriate patients can access the drug, the company has launched a patient support program called Interconnect. "Through Interconnect, dedicated Care Coordinators will guide patients through disease education, treatment support and, for eligible patients, financial assistance options, which may include reimbursement support, co-pay assistance or access to Ocaliva at no cost," the company said.

More information about the program and US distribution of obeticholic acid can be obtained by calling 1-844-622-4278 or visiting https://www.interconnectsupport.com/.

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