EU/3/09/657

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Orphan designation

On 24 July 2009, orphan designation (EU/3/09/657) was granted by the European Commission to BioMarin Europe Limited, United Kingdom, for recombinant human N-acetylgalactosamine-6-sulfatase for the treatment of mucopolysaccharidosis, type IVA (Morquio A syndrome).

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-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.

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

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).

What treatments are available?

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.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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.

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>Recombinant human N-acetylgalactosamine-6-sulfatase</p>
Active substanceRecombinant human N-acetylgalactosamine-6-sulfatase
Medicine NameVimizim
Disease/conditionTreatment of mucopolysaccharidosis, type IVA (Morquio A syndrome)
Date of decision24/07/2009
OutcomePositive
Orphan decision numberEU/3/09/657

Review of designation

During its meeting of 11 to 12 March 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/09/657 for Vimizim (elosulfase alfa, previously known as recombinant human N-acetylgalactosamine-6-sulfatase) as an orphan medicinal product for the treatment of mucopolysaccharidosis, type IVA (Morquio A syndrome). The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other satisfactory methods of treatment. The COMP recommended that the orphan designation of the medicine be maintained1.


1The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with a comparable therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Vimizim for the ‘treatment of mucopolysaccharidosis, type IVA (Morquio A Syndrome) in patients of all ages’.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of mucopolysaccharidosis, type IVA (Morquio A syndrome)’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2009. Mucopolysaccharidosis, type IVA remains a condition that is debilitating in the long term and life threatening, particularly because of damage to the spine and the heart, and problems with breathing.

Prevalence of the condition

The sponsor performed a search of the scientific literature and concluded that no publications are available which suggest a change in prevalence of mucopolysaccharidosis, type IVA.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of mucopolysaccharidosis, type IVA remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be approximately 0.03 people in 10,000. This is equivalent to a total of around 1,500 people in the EU.

Existence of other satisfactory methods of treatment

The COMP noted that, at the time of the review of the orphan designation, no satisfactory treatments were authorised in the EU for patients affected by mucopolysaccharidosis, type IVA.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Vimizim still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Related information

Sponsor’s contact details

BioMarin Europe Limited
164 Shaftesbury Avenue
London WC12 8HL
United Kingdom
Tel. +44 (0)20 7420 0800
Fax +44 (0)20 7420 0829
E-mail: biomarin-europe@bmrn.com

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.