EU/3/06/406: Orphan designation for the treatment of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis is a progressive disease of the nervous system that is caused by the gradual deterioration of specific nerve cells in the brain and spinal cord that control voluntary movement. The loss of these so-called motor neurons causes the muscles under their control to weaken and waste away, eventually leading to paralysis. Symptoms of amyotrophic lateral sclerosis vary from patient to patient, depending on which muscles weaken first. Symptoms may include tripping and falling, loss of motor control in hands and arms, difficulty in speaking, swallowing and/or breathing, persistent fatigue, and twitching and cramping. The reason why neurons deteriorate in amyotrophic lateral sclerosis is thought to be that defective (misfolded) protein molecules accumulate in these cells. Amyotrophic lateral sclerosis is chronically debilitating and life-threatening.

At the time of designation, amyotrophic lateral sclerosis affected approximately 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 28,000 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 468,900,000 (Eurostat 2006).

A medicinal product called riluzole was authorised for the condition in the Community at the time of submission of the application for orphan drug designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that arimoclomol might be of potential significant benefit for the treatment of amyotrophic lateral sclerosis. The benefit will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Misfolding of some proteins in motor-neurons is thought to be part of the development of amyotrophic lateral sclerosis. Arimoclomol is a small molecule that stimulates the production of so-called chaperones, which are proteins that help these proteins folding correctly. This is hoped to decrease the loss of motor-neurons, and thus improve the symptoms.

The effects of arimoclomol were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with amyotrophic lateral sclerosis were ongoing.

Arimoclomol was not authorised anywhere worldwide for the treatment of amyotrophic lateral sclerosis, at the time of submission. Orphan designation of arimoclomol was granted in the United States for the treatment of this condition.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 6 September 2006 a positive opinion recommending the grant of the above-mentioned 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 Community) 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.