EU/3/10/777: Orphan designation for the treatment of molybdenum-cofactor deficiency type A

Molybdenum cofactor deficiency is a genetic disease caused by the lack of a substance called 'molybdenum cofactor'. This is a molecule that is needed for the production of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Without these enzymes, the toxic chemical sulfite builds up in the brain

In the 'type A' form of the disease, the absence of molybdenum cofactor is due to patients lacking a substance called 'cyclic pyranopterin monophosphate'. The body needs this substance to make molybdenum cofactor.

The symptoms of molybdenum-cofactor deficiency appear from birth and include seizures (fits), intracranial haemorrhage (bleeding in the brain), increased reflex responses and feeding problems.

Molybdenum-cofactor deficiency type A is a very severe and life-threatening condition, which is associated with poor overall survival, with death usually occurring within the first few months of life.

At the time of designation, molybdenum cofactor deficiency type A affected less than 0.01 people in 10,000 per year in the European Union (EU)*. This is equivalent to a total of fewer than 500 people per year, which was considered to be below the threshold for orphan designation. This is based on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed on the basis of data from the European Union (EU 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of molybdenum-cofactor deficiency type A. Treatments aimed at relieving the symptoms of the disease, such as using medicines to control seizures, and at providing general support to help care for the patients.

To make this medicine, cyclic pyranopterin monophosphate is extracted from bacteria and then purified. It is expected to work by providing molybdenum-cofactor-deficiency-type-A patients with the substance that they are lacking. The body is expected to use this medicine to produce molybdenum cofactor, allowing it to start producing molybdenum-dependent enzymes and reducing the levels of sulfite in the brain.

At the time of submission of the application for orphan designation, the evaluation of the effects of cyclic pyranopterin monophosphate in experimental models was ongoing.

At the time of submission of the application for orphan designation, three patients had been treated with cyclic pyranopterin monophosphate.

At the time of submission, cyclic pyranopterin monophosphate was not authorised anywhere in the EU for the treatment of molybdenum-cofactor deficiency type A. Orphan designation of cyclic pyranopterin monophosphate had been granted in United States for the treatment of this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 2 June 2010 recommending the granting of this designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• either the rarity of the condition (affecting not more than 5 in 10,000 people in the EU) or insufficient returns on investment.

Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.