The U.S. Food and Drug Administration approved Cholbam (cholic acid) capsules, the first FDA approved treatment for pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders (including Zellweger spectrum disorders). Patients with these rare, genetic, metabolic conditions exhibit manifestations of liver disease, steatorrhea (presence of fat in the stool) and complications from decreased fat-soluble vitamin absorption.

Individuals with these rare disorders lack the enzymes needed to synthesize cholic acid, a primary bile acid normally produced in the liver from cholesterol. The absence of cholic acid in these patients leads to reduced bile flow, accumulation of potentially toxic bile acid intermediates in the liver (cholestasis), and malabsorption of fats and fat-soluble vitamins in the diet. If untreated, patients fail to grow and can develop life-threatening liver injury. 

Cholbam is approved as an oral treatment for children aged three weeks and older, and adults. The manufacturer of Cholbam was granted a rare pediatric disease priority review voucher–a provision that encourages development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.

“This approval underscores the agency’s commitment to making treatments available to patients with rare diseases,” said Julie Beitz, M.D., director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research (CDER). “Prior to today’s approval, patients with these rare bile acid synthesis disorders had no approved treatment options.”

The efficacy of Cholbam for the treatment of patients with bile acid synthesis disorders due to single enzyme defects was assessed in an uncontrolled trial involving 50 patients treated over an 18 year period. An extension trial followed 21 of these patients and enrolled an additional 12 patients with interim efficacy data available for an additional 21 months. On average, patients were 4 years of age at the start of cholic acid treatment (range 3 weeks to 36 years). Response to treatment was evaluated by improvements in baseline liver function tests and weight. Responses were noted in 64 percent of patients with evaluable data. Two-thirds of patients survived greater than three years. Literature reports also supported the efficacy of Cholbam in this population.

The efficacy of Cholbam for the treatment of peroxisomal disorders, including Zellweger spectrum disorders, was assessed in an uncontrolled, treatment trial involving 29 patients treated over an 18 year period. An extension trial followed 10 of these patients and enrolled an additional two patients with interim efficacy data available for 21 additional months. The majority of patients were less than 2 years of age at the start of cholic acid treatment (range 3 weeks to 10 years). Response to treatment was evaluated by improvements in baseline liver function tests and weight. Responses were noted in 46 percent of patients with evaluable data.  Forty-two percent of patients survived greater than 3 years. 

Cholbam did not affect other manifestations of bile acid disorders due to single enzyme defects or peroxisomal disorders such as neurologic symptoms.

The most common side effect in patients treated with Cholbam was diarrhea. The use of Cholbam should be carefully monitored by an experienced hepatologist or pediatric gastroenterologist, and treatment discontinued in patients developing worsening liver function.

An observational study to assess the long-term safety of Cholbam will be required post-approval.

Cholbam is marketed by Baltimore, Maryland-based Asklepion Pharmaceuticals LLC.