EU/3/09/657: Orphan designation for the treatment of mucopolysaccharidosis, type IVA (Morquio A syndrome)

Mucopolysaccharidosis type IVA (also known as 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). Because patients with mucopolysaccharidosis type IVA cannot break these substances down, the GAGs gradually build up in most of the bones and organs in the body and damage them. This causes 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 affected less than 1.5 in 10,000 people in the European Union (EU). This was equivalent to a total of 76,000 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).

*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 504,800,000 (Eurostat 2009).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of mucopolysaccharidosis type IVA. Treatments were aimed at relieving the symptoms of the disease, and included surgery, medicines to fight infection and reduce inflammation and pain, and oxygen for patients with breathing problems.

Recombinant human N-acetylgalactosamine-6-sulfatase is expected to act in the same way as the human enzyme N-acetylgalactosamine-6-sulfatase, which is missing in patients with mucopolysaccharidosis type IVA. The replacement enzyme is expected to help to break down GAGs and stop them accumulating in the body, relieving the symptoms of the disease.

This medicine is a copy of the human enzyme that has been produced by a method known as 'recombinant DNA technology': it is made by a cell that has received a gene (DNA), which makes it able to produce the human enzyme N-acetylgalactosamine-6-sulfatase.

The effects of recombinant human N-acetylgalactosamine-6-sulfatase have been evaluated in experimental models.

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, recombinant human N-acetylgalactosamine-6-sulfatase was not authorised anywhere in the EU for mucopolysaccharidosis type IVA or designated as 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 4 June 2009 recommending the granting of this designation.

Update: Recombinant human N-acetylgalactosamine-6-sulfatase (Vimizim) has been authorised in the EU since 28 April 2014 for the treatment of mucopolysaccharidosis, type IVA (Morquio A Syndrome, MPS IVA) in patients of all ages.

More information on Vimizim can be found in the European public assessment report (EPAR) on the Agency's website.

• 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 Community) 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.