EU/3/18/2115: Orphan designation for the treatment of spinal muscular atrophy

Spinal muscular atrophy is an inherited disease usually diagnosed in the first year of life 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.

Spinal muscular atrophy is a long-term debilitating and life-threatening disease because it causes breathing problems and muscle wasting that worsens over time.

At the time of designation, spinal muscular atrophy affected approximately 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 21,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 517,400,000 (Eurostat 2018).

At the time of designation, one medicine, Spinraza, was authorised for the treatment of spinal muscular atrophy. Patients also 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 muscle function, and ventilators to help with breathing.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with spinal muscular atrophy. Early laboratory data indicate that the medicine may improve muscle mass and muscle strength in patients who cannot be treated with the authorised medicine.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is a monoclonal antibody (a type of protein) that has been designed to recognise, attach to and block a protein called promyostatin. Promyostatin is the inactive form of myostatin, a protein present in muscle cells that prevents muscle growth and regeneration. By blocking promyostatin, the medicine is expected to increase muscle mass and strength in patients with spinal muscular atrophy.

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with spinal muscular atrophy had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for spinal muscular atrophy. Orphan designation of the medicine had been granted in the United States for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 November 2018 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.