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Orphan designation

On 27 February 2009, orphan designation (EU/3/09/615) was granted by the European Commission to Arndt Rolfs, Germany, for N-terminal hexaglutamine-tagged recombinant human N-acetylgalactosamine-6-sulfate sulfatase for the treatment of mucopolysaccharidosis type IVA (Morquio A syndrome).

The sponsorship was transferred to Dr Gosse B. Bruinsma, The Netherlands, in May 2009 and to Dr Ulrich Granzer, in December 2010.

What is 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-sulfate 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, deformity of the spine, shortened bones, bell-shaped chest, short neck, difficulty moving, difficulty breathing, clouding of the eyes and hearing loss. The disease differs from other mucopolysaccharidosis in that it does not affect the intelligence of the patient. 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.

What is the estimated number of patients affected by the condition?

At the time of designation, mucopolysaccharidosis type (IVA Morquio A syndrome) affected approximately 1.5 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 76,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and 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. This represents a population of 504,800,000 (Eurostat 2009).

What treatments are available?

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

How is this medicine expected to work?

N-terminal hexaglutamine-tagged recombinant human N-acetylgalactosamine-6-sulfate sulfatase is expected to act in the same way as the human enzyme N-acetylgalactosamine-6-sulfate sulfatase, which is missing in patients with mucopolysaccharidosis type IVA. The replacement enzyme is expected to help 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-sulfate sulfatase. The enzyme has been ‘tagged’ on one side with six molecules of glutamine (hexaglutamine) so that it may remain active for longer in the bones.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the effects of N-terminal hexaglutamine-tagged recombinant human N-acetylgalactosamine-6-sulfate sulfatase had been evaluated in experimental models, and no clinical trials had been started.

At the time of submission, the medicine was not authorised anywhere in the world for mucopolysaccharidosis type IVA. Orphan designation of recombinant human N-acetylgalactosamine-6-sulfate sulfatase had been granted in the United States of America for mucopolysaccharidosis type IVA.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 January 2009 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:
  • 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.

Key facts

Product details for <p>N-terminal hexaglutamine-tagged recombinant human N-acetylgalactosamine-6-sulfate sulfatase</p>
Active substanceN-terminal hexaglutamine-tagged recombinant human N-acetylgalactosamine-6-sulfate sulfatase
Medicine Name
Disease/conditionTreatment of mucopolysaccharidosis type IVA (Morquio A syndrome)
Date of decision26/02/2009
Orphan decision numberEU/3/09/615

Review of designation

Sponsor’s contact details

Dr Ulrich Granzer
Mauerkircherstrasse 10
81925 Munich
Tel. +49 8978 0689820
Fax +49 8978 0689815

Patients’ organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe.
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.