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Cholbam (Cholic Acid) Wins FDA Nod for Treatment of Rare Bile Acid Synthesis Disorders

Agency asks for post-approval safety study

The FDA has approved Cholbam (cholic acid, Asklepion Pharmaceuticals) 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, and complications from decreased fat-soluble vitamin absorption.

Individuals with these 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, to the accumulation of potentially toxic bile acid intermediates in the liver (cholestasis), and to the 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 3 weeks of age and older, and for adults.

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 during an 18-year period. An extension trial followed 21 of these patients and enrolled an additional 12 patients; interim efficacy data from this study were 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). The response to treatment was evaluated by improvements in baseline liver-function tests and weight. Responses were observed in 64% of patients with evaluable data. Two-thirds of the patients survived for longer than 3 years.

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

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

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

The FDA is requiring a post-approval, observational study to assess the long-term safety of Cholbam.

Source: FDA; March 17, 2015.

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