EU/3/14/1399: Orphan designation for the treatment of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive disease of the nervous system, where nerve cells in the brain and spinal cord that control voluntary movement gradually deteriorate, causing loss of muscle function and paralysis. The exact causes are unknown but are believed to include genetic and environmental factors. The symptoms of ALS vary depending on which muscles weaken first, and include loss of balance, loss of control of hand and arm movement, and difficulty speaking, swallowing and breathing. ALS usually starts in mid-life and men are more likely to develop the disease than women.

ALS is a long-term debilitating and life-threatening disease because of the gradual loss of function and its paralysing effect on muscles used for breathing which usually leads to death due to respiratory failure.

At the time of designation, ALS affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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 511,100,000 (Eurostat 2014).

At the time of designation, riluzole was authorised in the EU to treat ALS. Patients also received supportive treatment to temporarily relieve the symptoms of the disease, such as physiotherapy and speech therapy.

The sponsor has provided sufficient information to show that edaravone might be of significant benefit for patients with the condition based on data from early studies that showed potential favourable effects of using edaravone in combination with riluzole treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Damage to nerve cells in ALS appears to have several causes but there is evidence that it may involve damage to nerves caused by toxic molecules containing oxygen. In some patients this is associated with a defect in the gene responsible for producing the enzyme called superoxide dismutase (SOD), which causes the enzyme to clump together inside nerve cells. This leads to inflammation and kills the affected nerve cells. Edaravone is expected to act as an antioxidant, a molecule that can prevent damage to nerve cells caused by oxygen-containing molecules, and also blocks the clumping together of SOD in the nerves and so reduces inflammation.

Edaravone has been authorised in Japan to reduce nerve damage caused by acute ischaemic stroke (stroke caused by failure of the blood supply to part of the brain).

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

At the time of submission, no clinical trials with edaravone in patients with ALS were ongoing.

At the time of submission, edaravone was not authorised anywhere in the EU for ALS. Orphan designation had been granted in Japan for ALS.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 November 2014 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.