EU/3/12/976: Orphan designation for the treatment of 5q spinal muscular atrophy

5q spinal muscular atrophy is an inherited disease that affects the motor neurons (nerves from the brain and spinal cord that control muscle movements). Patients with the disease lack a protein called 'survival motor neuron' (SMN), which is essential for the normal functioning and survival of motor neurons. Without this protein, the motor neurons deteriorate and eventually die. This causes the muscles to fall into disuse, leading to muscle wasting (atrophy) and weakness. Muscle weakness is usually more severe in the proximal musculature (the muscles closest to the trunk). The disease is linked to a defect on chromosome 5q and is usually diagnosed in the first year of life.

5q spinal muscular atrophy is a long-term debilitating and life-threatening disease because it causes breathing problems and paralysis that worsens over time.

At the time of designation, 5q spinal muscular atrophy affected less than 0.4 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 20,000 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. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, no satisfactory methods were authorised in the EU for the treatment of 5q spinal muscular atrophy. Patients received supportive treatment to help them and their families cope with the symptoms of the disease. This included chest physiotherapy and physical aids to support muscular function, and ventilators to help with breathing.

The SMN protein is made by two genes, the SMN1 and SMN2 genes. Most patients with 5q spinal muscular atrophy lack the SMN1 gene but have the SMN2 gene, which mostly produces a 'short' SMN protein which cannot work properly.

This medicine is an 'anti-sense oligonucleotide' medicine. It is expected to make the SMN2 gene produce adequate levels of the SMN protein of normal length, thereby increasing the survival of motor neurons. It is expected to do so by blocking the cutting ('splicing') of the molecule produced from the SMN2 gene that serves as the 'template' for the SMN protein. This is expected to lead to an increased production of the normal-length SMN protein.

This medicine is expected to be given by injection into the fluid surrounding the spinal cord and brain.

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicinal product in experimental models was ongoing.

At the time of submission, no clinical trials with the medicinal product in patients with 5q spinal muscular atrophy had been started.

At the time of submission, the medicinal product was not authorised anywhere in the EU for the treatment of 5q spinal muscular atrophy. Orphan designation of the medicinal product had been granted in the United States of America for the treatment of 5q spinal muscular atrophy.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 February 2012 recommending the granting of this designation.

• 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.