Cholbam Approved for Rare Metabolic Disorders


March 17, 2015

The US Food and Drug Administration (FDA) today approved cholic acid capsules (Cholbam, Asklepion Pharmaceuticals) for two rare metabolic disorders that stymie the body's production of this acid and may lead to life-threatening liver damage, the agency announced.

Cholic acid capsules are indicated for children aged 3 weeks or older and adult patients who have bile acid synthesis disorders caused by single enzyme defects, or who have peroxisomal disorders. Peroxisomes are cellular organelles that aid in metabolism and help produce bile acids, cholesterol, and plasmalogens. Peroxisomal disorders include so-called Zellweger spectrum disorders such as Zellweger syndrome, characterized by abnormal facial features, an enlarged liver, and nerve damage in infants.

With both sets of rare congenital disorders, individuals lack enzymes needed to synthesize cholic acid, a primary bile acid, according to the FDA. A lack of cholic acid results in reduced bile flow, accumulation of potentially toxic bile-acid intermediates in the liver, and malabsorption of fats and fat-soluble vitamins in food.

The FDA approved cholic acid capsules as part of a review process that gives a high priority to treatments for rare pediatric diseases. As a condition of approval, the manufacturer now must conduct an observational study to assess the treatment's long-term safety.

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

The agency determined that cholic acid capsules were effective in treating bile acid synthesis disorders due to single enzyme defects based on an uncontrolled trial involving 50 patients treated over 18 years. Roughly two-thirds of patients whose data could be evaluated showed improvements in baseline liver function tests and weight.

The efficacy of cholic acid capsules for peroxisomal disorders was studied in another uncontrolled trial with 29 patients who were treated over 18 years. Here, 46% of patients with evaluable data responded to treatment with improved liver function tests and weight gain.

Diarrhea was the most common adverse event observed in the trials.

An experienced hepatologist or pediatric gastroenterologist should monitor the use of cholic acid capsules, the FDA said, and discontinue them if a patient's liver function worsens.

More information on today's announcement is available on the agency's website.


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