EU/3/01/022

On 14 February 2001, orphan designation (EU/3/01/022) was granted by the European Commission to Genzyme BV, the Netherlands, for laronidase for the treatment of mucopolysaccharidosis, type I. The sponsor changed its name to Genzyme Europe BV in 2002.

What is mucopolysaccharidosis, type I?

The 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.

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

At the time of designation mucopolysaccharidosis, type I affected approximately 0.025 in 10,000 people in the European Union (EU) *. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 950 people.

* Disclaimer: The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 377,000,000 (Eurostat 2001) and may differ from the true number of patients affected by the condition.

What treatments are available?

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 a majority of mucopolysaccharidosis type I patients were limited to symptomatic care and occasionally bone-marrow transplantation.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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 was 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.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 19 December 2000 a positive opinion recommending the grant of the above-mentioned designation.

Update: Laronidase (Aldurazyme) has been authorised in the EU since 10 June 2003 for long-term enzyme replacement therapy in patients with a confirmed diagnosis of mucopolysaccharidosis I (MPS I; a [alpha]-L-iduronidase deficiency) to treat the non-neurological manifestations of the disease.

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;
• 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.