This article is more than 5 years old. Information may no longer be current.
FDA Approves Ocaliva for Primary Biliary Cholangitis
Click Here to Manage Email Alerts
The FDA announced it granted accelerated approval for Ocaliva for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid for adults who failed therapy with ursodeoxycholic acid alone, or as a single therapy in adults intolerable to ursodeoxycholic acid.
Ocaliva (obeticholic acid, Intercept Pharmaceuticals) binds to the farnesoid X receptor and 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, according to a press release from the FDA.
The FDA’s approval is indicative of obeticholic acid successfully reducing alkaline phosphatase (ALP) in patients with PBC, which can ultimately lead to improved transplant free-survival.
“Patients left untreated, or who have not responded to [ursodeoxycholic acid], are at risk for liver failure and death,” Amy Egan, MD, MPH, deputy director of the office of drug evaluation III in the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Ocaliva provides an important treatment option for patients living with PBC who have not responded to the only other approved therapy, [ursodeoxycholic acid].”
Ursodeoxycholic acid (UDCA) is the only other treatment available for PBC and was approved by the FDA in 1997. UDCA is effective in more than 50% of patients. However, up to 40% do not experience reduced ALP or total bilirubin, and between 5% and 10% are unable to tolerate it, according to the FDA.
The safety and efficacy of obeticholic acid were demonstrated in a clinical trial with 216 patients with PBC. After 1 year, the number of patients with PBC treated with obeticholic acid who achieved reductions in ALP levels was greater compared with patients treated with placebo. Common adverse events were pruritus, fatigue, abdominal pain and discomfort, arthralgia, oropharyngeal, dizziness and constipation. Ocaliva should not be used in patients with complete biliary obstruction, according to the FDA.
Data from the POISE clinical trial presented at the International Liver Congress showed a titration strategy — patients initiated obeticholic acid at 5 mg and titrating up to 10 mg based on clinical response at 6 months — helped reduce the incidence and severity of pruritus in patients treated with obeticholic acid.
“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," John Vierling, MD, FACP, FAASLD, professor of medicine and surgery at Baylor College of Medicine, said in a press release from Intercept Pharmaceuticals. “Importantly, Ocaliva maintained durable ALP reductions, which is critical for treatment of a chronic disease like PBC.”
Linie Moore, president of the PBCers Organization, said in the Intercept release, “PBC affects people in the prime of their lives and, for some, the potential need for a liver transplant is a constant concern during these important years. After nearly two decades with only one approved treatment, we are thrilled to welcome this important new medicine for people living with PBC.”
The Gastrointestinal Drugs Advisory Committee recently recommended the FDA approve obeticholic acid for use as monotherapy or in combination with ursodeoxycholic acid for the treatment of adults with PBC.
Obeticholic acid is expected to be available to patients with PBC within 7 to 10 days and will be distributed through a specialty pharmacy network, according to Intercept.
Disclosure: Healio.com/Hepatology was unable to confirm relevant financial disclosures at the time of publication.
Perspective
Back to Top
Kris V. Kowdley, MD
The approval of Ocaliva represents an important new therapeutic option for patients with primary biliary cholangitis. The only approved therapy for the past 20 years has been ursodeoxycholic acid (UDCA), which is effective in slowing the progression of liver disease and can normalize liver tests in many patients. However, up to 40% of patients are unresponsive to or intolerant of UDCA.
Ocaliva (obeticholic acid, Intercept Pharmaceuticals) was shown to improve serum alkaline phosphatase to 1.67 times the upper limits of normal with at least a 15% reduction in the level along with a serum bilirubin less than the upper limits of normal in a randomized trial of patients treated with UDCA at a dose of 5 to 10 mg per day.
The main side effect is pruritus, which is dose-related and can be managed in most patients with standard measures. Discontinuations due to pruritus are uncommon.
A clinical trial to assess the effect of Ocaliva therapy on clinical outcomes is underway.
Ocaliva represents an important therapeutic advance for patients with PBC in need of additional therapies.
Click Here to Manage Email Alerts