EU/3/04/260: Orphan designation for the treatment of alpha-mannosidosis

α-mannosidosis is an inherited disease leading to an accumulation of oligosaccharides (small molecules composed of sugars) in the body. α-mannosidosis is due to a lack of α-mannosidase, an enzyme (a protein that speed up the conversion of certain substances into other substances) needed for the breaking down of oligosaccharides. The most severe form (type 1) occurs before 1 year of age. Clinical features include deafness and profound mental retardation. The juvenile/adult form (type 2) is less severe. Milder mental retardation occurs later, but hearing loss is a prominent feature. α-mannosidosis is chronically debilitating and life-threatening.

At the time of designation, α-mannosidosis affected approximately 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of around 470 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 466,600,000 (Eurostat 2005).

At the time of submission of the application for the orphan drug designation there was no treatment authorised in the European Union. Treatment of α-mannosidosis included supportive care and bonemarrowtransplantation.

It is assumed that, once admininistrated to the patient, recombinant human α-mannosidase will act as the original α-mannosidase and break down the oligosaccharides, thus preventing the negative effects due to their accumulation in the body.

The evaluation of the effects of recombinant human α-mannosidase in experimental models is ongoing.

At the time of submission of the application for orphan designation, no clinical trials in patients with α-mannosidosis were initiated.

Recombinant human α-mannosidase was not marketed anywhere worldwide for α-mannosidosis or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 December 2004 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.