EU/3/18/2047: Orphan designation for the treatment of phosphomannomutase 2-congenital disorder of glycosylation

Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CGD) belongs to a group of inherited disorders that are caused by the lack of an enzyme involved in the glycosylation process. Glycosylation involves attachment of sugars to certain proteins or fats (lipids) to enable them to carry out various essential functions in the body.

In PMM2-CDG, an enzyme called phosphomannomutase 2 does not work correctly, meaning that a sugar needed for glycosylation, called mannose-1-phosphate, cannot be formed. This prevents glycosylation of various proteins essential for development and normal body function, leading to symptoms including delayed development, intellectual disability, bone and joint deformities, fits, problems with vision and coordination, and liver, heart and circulatory problems.

PMM2-CDG is a long-term debilitating and life-threatening disease because of damage to various organs and tissues.

At the time of designation, PMM2-CDG affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,000 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).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of PMM2-CDG. Patients were given supportive care including occupational, physical and speech therapy, and feeding via a tube where necessary.

The medicine is made of the sugar mannose-1-phosphate, which patients cannot make for themselves because they do not have a working phosphomannomutase 2 enzyme. The sugar is encapsulated in fatty particles called ‘liposomes’ which protect it from being broken down and allow it to be delivered into liver cells where most glycosylation takes place. The medicine is expected to work by replacing the missing sugar and allowing the glycosylation process to proceed normally. This is expected to relieve the symptoms of PMM2-CDG.

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with PMM2-CDG had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for PMM2-CDG or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 21 June 2018 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.