EU/3/19/2238: Orphan designation for the treatment of mucopolysaccharidosis type IVA (Morquio A Syndrome)

Mucopolysaccharidosis type IVA (Morquio A Syndrome) is an inherited disease that is caused by the lack of an enzyme called N-acetylgalactosamine-6-sulfatase. This enzyme is needed to break down substances in the body called glycosaminoglycans (GAGs). Patients with mucopolysaccharidosis type IVA cannot break these substances down, and thereby the GAGs gradually build up in most of the bones and organs in the body, causing a wide range of symptoms, including dwarfism, deformities in the spine, shortened bones, a bell-shaped chest, a short neck, difficulty moving, difficulty breathing, clouding of the eyes and hearing loss. The disease differs from other types of mucopolysaccharidosis in that it does not affect the patient's intelligence. It is usually diagnosed in infants between two and three years of age.

Mucopolysaccharidosis type IVA is a debilitating disease that is long lasting and may be life threatening because of the damage to the spine and the heart, and problems with breathing.

At the time of designation, mucopolysaccharidosis type IVA (Morquio A Syndrome) affected less than 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 5,200 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 28), Norway, Iceland and Liechtenstein. This represents a population of 518,400,000 (Eurostat 2019).

At the time of designation, Vimizim (elosulfase alfa), an enzyme replacement therapy, was authorised in the EU for treating for mucopolysaccharidosis type IVA.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with this condition. This is because available evidence indicates that a single administration may help restore levels of N-acetylgalactosamine-6-sulfatase over the long term, reducing the need for regular treatment.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of a virus containing the gene for N-acetylgalactosamine-6-sulfatase enzyme, which is lacking in patients with mucopolysaccharidosis type IVA. When given to the patient, the virus is expected to carry the gene into the patient’s cells, enabling these cells to start producing the enzyme. The enzyme is then expected to help breakdown GAGs, thereby helping to relieve symptoms of the disease.

The type of virus used in this medicine ('adeno-associated virus') does not cause disease in humans.

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

At the time of submission of the application for orphan designation, no clinical trials in patients with mucopolysaccharidosis type IVA had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of mucopolysaccharidosis type IVA. Orphan designation for the condition had been granted in the United States.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 5 December 2019, 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.