Today 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.
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.
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.
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.”
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
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.
did not affect other manifestations of bile acid disorders due to single enzyme
defects or peroxisomal disorders such as neurologic symptoms.
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.
observational study to assess the long-term safety of Cholbam will be required
is marketed by Baltimore, Maryland-based Asklepion Pharmaceuticals LLC.
FDA, an agency within the U.S. Department of Health and Human Services,
protects the public health by assuring the safety, effectiveness, and security
of human and veterinary drugs, vaccines and other biological products for human
use, and medical devices. The agency also is responsible for the safety and
security of our nation’s food supply, cosmetics, dietary supplements, products
that give off electronic radiation, and for regulating tobacco products.