EU/3/20/2284: 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 depend 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 midlife and men are more likely to develop the disease than women.

ALS is a 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 from 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 52,000 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).

^*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

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

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with ALS. Studies showed that the medicine could improve strength of arms and lung function in patients being treated with riluzole. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is made up of two substances: sodium phenylbutyrate and tauroursodeoxycholic acid. How the medicine works is not fully clear, but it is expected to reduce nerve cell stress and prevent nerve cells from dying. This is expected to improve symptoms of the disease.

The effects of sodium phenylbutyrate and tauroursodeoxycholic acid have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with ALS were ongoing.

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

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 23 April 2020, 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.