EU/3/13/1144

On 19 June 2013, orphan designation (EU/3/13/1144) was granted by the European Commission to Synageva BioPharma Ltd, United Kingdom, for recombinant human alpha-N-acetylglucosaminidase for the treatment of mucopolysaccharidosis type IIIB (Sanfilippo B syndrome).

The sponsorship was transferred to Alexion Europe SAS, France, in October 2015.

What is mucopolysaccharidosis type IIIB (Sanfilippo B syndrome)?

Mucopolysaccharidosis type IIIB (also known as Sanfilippo B syndrome) is an inherited disease that is caused by the lack of an enzyme called alpha-N-acetylglucosaminidase. This enzyme is needed to break down a substance in the body called heparan sulphate. Because patients with mucopolysaccharidosis type IIIB cannot break this substance down, it gradually builds up in cells in the body, particularly in the brain, and damages them. This causes a wide range of symptoms, including behavioural problems, learning disabilities and sleep disturbances.

Symptoms of mucopolysaccharidosis type IIIB typically start in children between three and six years of age. It is a seriously debilitating and life-threatening disease that progress to serious mental disability. The disease usually leads to death during youth.

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

At the time of designation, mucopolysaccharidosis type IIIB affected approximately 0.02 in 10,000 people in the European Union (EU). This was equivalent to a total of around 1,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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. At the time of designation, this represented a population of 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU for treating mucopolysaccharidosis type IIIB.

How is this medicine expected to work?

The medicine consists of a copy of the enzyme, alpha-N-acetylglucosaminidase, which is missing in patients with mucopolysaccharidosis type IIIB. When it is given to the patient (either into a vein or into the space that surrounds the spinal cord), it is expected to replace the missing enzyme thereby slowing down the build-up of heparan sulphate. This is expected to reduce the symptoms of the disease.

The medicine is produced by a method known as ‘recombinant DNA technology’: it is purified from the egg white of hens into which a gene (DNA) has been introduced, which makes them able to produce the enzyme.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of recombinant human alpha-N-acetylglucosaminidase in experimental models was ongoing.

At the time of submission of the application for orphan designation, no clinical trials with recombinant human alpha-N-acetylglucosaminidase in patients with mucopolysaccharidosis type IIIB had been started.

At the time of submission, recombinant human alpha-N-acetylglucosaminidase was not authorised anywhere in the EU for mucopolysaccharidosis type IIIB 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 15 May 2013 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 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.