EU/3/19/2145: 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 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).

At the time of designation, the medicine Spinraza (nusinersen) was authorised for the treatment of spinal muscular atrophy. Spinraza is given by injection into the spine. 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 data indicate that the medicine may improve patients’ survival and muscle strength compared with results seen with the authorised treatment; additionally, since the medicine is to be given by mouth, it may be usable in a broader population. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The SMN protein can be made by two genes, SMN1 and SMN2. Patients with spinal muscular atrophy lack a working SMN1 gene but have the SMN2 gene, which mostly produces a short SMN protein that does not work as well as a full-length protein.

Risdiplam is a small molecule that enables the SMN2 gene to produce a full length protein, which is able to work normally. This is expected to increase survival of motor neurons and reduce symptoms of the disease.

The effects of risdiplam have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with risdiplam in patients with spinal muscular atrophy were ongoing.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 24 January 2019 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.