EU/3/15/1459: 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 not more than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 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 512,900,000 (Eurostat 2015).

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 enoxacin might be of significant benefit for patients with the condition because early studies in experimental models showed that the medicine may delay the onset of symptoms and improve muscle function. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Enoxacin is an antibiotic used to treat a variety of bacterial infections. Apart from its antibacterial activity, studies have shown that enoxacin can increase the activity of an enzyme called 'dicer', which cuts the RNA (the genetic material that guides the production of proteins) in small fragments called siRNA and miRNA, which are involved in the production of proteins. In patients with ALS, miRNA is produced at a reduced rate, and this is thought to contribute to the deterioration of the nerve cells and the development of the disease. By increasing the activity of dicer, enoxacin is expected to increase the levels of miRNA, therefore slowing down the progression of the disease.

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 ASL had been started.

At the time of submission, the medicine was not authorised anywhere in the EU for ALS or designated as an orphan medicinal product elsewhere for this condition. Enoxacin was authorised in some EU member states for the treatment of bacterial infections.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 February 2015 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.