On 25 May 2012, the European Commission adopted a decision to refuse the granting of a marketing authorisation for the medicinal product Orphacol, intended for the treatment of inborn errors in primary bile acid synthesis. The company that applied for authorisation is Laboratoires CTRS.
- What is Orphacol?
Orphacol is a medicine that contains the active substance cholic acid. It was to be available as capsules (50 mg and 250 mg).
- What was Orphacol expected to be used for?
Orphacol was expected to be used to treat adults and children from one month of age with a condition known as ‘inborn errors in primary bile acid synthesis’. These patients are born with a genetic abnormality that makes them unable to produce bile, a fluid that helps digestion. Orphacol was expected to be used in patients who do not have enough of two specific liver enzymes (3β-hydroxy-Δ5-C27-steroid oxidoreductase or Δ4-3-oxosteroid-5β-reductase). This makes their liver unable to produce enough of the main components of bile, called primary bile acids, such as cholic acid. When these primary bile acids are lacking, the body produces abnormal bile acids, which can damage the liver, potentially leading to life-threatening liver failure.
Because the number of patients with inborn errors in primary bile acid synthesis is low, the condition is considered ‘rare’, and Orphacol was designated an ‘orphan medicine’ (a medicine used in rare diseases) on 18 December 2002.
- How is Orphacol expected to work?
Cholic acid is the main primary bile acid produced by the liver. The cholic acid contained in Orphacol is expected to replace the patient’s missing cholic acid. This helps to decrease the production of abnormal bile acids and contributes to the normal activity of bile in the digestive system, thereby relieving the symptoms of the condition.
- What did the company present to support its application?
To support this application the company presented data from the scientific literature on the use of cholic acid in medical practice. The company identified 49 cases of patients treated for inborn errors in primary bile acid synthesis (38 patients with 3β-hydroxy-Δ5-C27-steroid oxidoreductase deficiency, and 11 patients with Δ4-3-oxosteroid-5β-reductase deficiency). It compared the outcomes of 28 patients who received cholic acid with others who were given different bile acids or did not receive bile acid treatment. In the literature, cholic acid treatment was shown to reduce the amount of abnormal bile acids in patients, to restore the normal functions of the liver and to help delay or prevent the need for a liver transplant.
- What were the main considerations that led to the refusal?
The CHMP noted that cholic acid had been used in medical practice to treat inborn errors in primary bile acid synthesis, as documented in the scientific literature, although the Committee acknowledged that the number of documented cases was low due to the rarity of the condition. It considered that, based on the information from the scientific literature, Orphacol’s benefits are greater than its risks and recommended that it be given marketing authorisation under ‘exceptional circumstances’.
On 25 May 2012 The European Commission adopted a decision to refuse the granting of a marketing authorisation for Orphacol. The Commission considered that the conditions for granting a marketing authorisation had not been met. The detailed reasons for the decision can be found in the Community register of medicinal products.
|International non-proprietary name (INN) or common name|
|Therapeutic area||Digestive System DiseasesMetabolism, Inborn Errors|
|Date of initial refusal|
|Date of confirmation||12/06/2012|
|Name||Language||First published||Last updated|
|Orphacol : EPAR - Public assessment report||(English only)||28/08/2012|