EU/3/01/022: Orphan designation for the treatment of mucopolysaccharidosis type I

Human cells contain various structures with specific functions known as organelles. Lysosomes are an example of such organelles. Lysosomes contain enzymes (biological catalysts that speed up chemical reactions in the body) essential for breaking down substances like proteins and sugars. Mucopolysaccharidosis type I belongs to a group of mucopolysaccharide storage disorders, characterised by deficiencies of certain lysosomal enzymes. Mucopolysaccharidosis type I is caused by the deficiency of the lysosomal enzyme α-L-iduronidase. Patients with mucopolysaccharidosis type I are classified into three clinical syndromes- Hurler, Hurler-Scheie and Scheie. Severe progressive skeletal disease and joint stiffness are two of the main features of mucopolysaccharidosis type I. Mucopolysaccharidosis type I is serious, chronically debilitating and, in most cases, life-threatening.

At the time of designation, mucopolysaccharidosis, type I affected approximately 0.025 in 10,000 people in the European Union (EU). This was equivalent to a total of around 950 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. At the time of designation, this represented a population of 378,800,000 (Eurostat 2001).

No medicinal products were authorised for the treatment of mucopolysaccharidosis type I in the Community at the time of submission of the application for orphan-drug designation. The treatment options for the majority of mucopolysaccharidosis-type-I patients were limited to symptomatic care and occasionally bone-marrow transplantation.

The active ingredient of laronidase is the enzyme α-L-iduronidase. α-L-iduronidase is the deficient enzyme in patients with mucopolysaccharidosis type I. By replacing the deficient enzyme with a functioning one, the sponsor hopes to restore the normal lysosomal function and ultimately improve the overall outcome of the patients.

The effects of laronidase were evaluated in experimental models.

At the time of submission of the application for orphan designation, one clinical trial in patients with mucopolysaccharidosis type I had been completed.

Laronidase was not marketed anywhere worldwide for treatment of mucopolysaccharidosis type I, at the time of submission.

Orphan designation of laronidase was granted in the United States for the condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 19 December 2000 recommending the granting of this designation.

Update: Laronidase (Aldurazyme) was authorised in the European Union on 10 June 2003 for long-term enzyme replacement therapy in patients with a confirmed diagnosis of mucopolysaccharidosis I (MPS I; α-L-iduronidase deficiency) to treat the nonneurological manifestations of the disease.

More information on Aldurazyme can be found in the European public assessment report (EPAR).

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.