EU/3/01/025: Orphan designation for the treatment of mucopolysaccharidosis VI (Maroteaux-Lamy syndrome)

Human cells contain various structures with specific functions known as organelles; lysosomes are such organelles. Lysosomes are small vesicles within cells containing enzymes that are able to destroy or transform different substances of the cell, such as proteins, fat, nucleic acids (components of the genetic material) and sugars. Any change of the lysosomal enzymes causes abnormal accumulation of the substance (also known as substrate) normally transformed by it. Cells are unable to destroy or eliminate accumulated substrates, and high levels of them can be toxic leading to damage and malfunction of the organ where accumulation occurs. Mucopolysaccharidosis, type VI (Maroteaux-Lamy syndrome) is a disorder caused by the lack of N-acetylgalactosamine-4-sulfatase in the lysosomes. Main clinical features of the disease include skeletal deformities and heart and lung problems as a consequence of the accumulation of substances normally broken down. Mucopolysaccharidosis, type VI (Maroteaux-Lamy syndrome) is chronically debilitating and life-threatening.

At the time of designation, mucopolysaccharidosis, type VI (Maroteaux-Lamy syndrome) affected between 0.0088 and 0.024 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 330 to 900 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: 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.

No medicinal products were authorised for the treatment of mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) in the Community at the time of submission of the application for orphan drug designation.

N-acetylgalactosamine-4-sulfatase is the deficient enzyme in patients with mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome). By replacing the deficient enzyme with a functioning one, it is expected to restore the normal lysosomal function and ultimately improve the overall health of the patients.

The effects of N-acetylgalactosamine-4-sulfatase were evaluated in experimental models. At the time of submission of the application for orphan designation, no clinical trials in patients with mucopolysaccharidosis, type VI (Maroteaux-Lamy syndrome) were initiated.
N-acetylgalactosamine-4-sulfatase was not marketed anywhere worldwide for treatment of mucopolysaccharidosis, type VI (Maroteaux-Lamy syndrome), at the time of submission. Orphan designation of N-acetylgalactosamine-4-sulfatase 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: N-acetylgalactosamine-4-sulfatase (Naglazyme) has been authorised in the EU since 24 January 2006 for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis VI (MPS VI; N-acetylgalactosamine 4-sulfatase deficiency; Maroteaux-Lamy syndrome).

More information on Naglazyme can be found in the European public assessment report (EPAR) on the Agency's website

• 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.