EU/3/15/1527

On 28 July 2015, orphan designation (EU/3/15/1527) was granted by the European Commission to PBS Regulatory Consulting Group Limited, United Kingdom, for hydrocinnamate-[Orn-Pro-dCha-Trp-Arg]acetate for the treatment of amyotrophic lateral sclerosis.

What is 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.

What is the estimated number of patients affected by the condition?

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 isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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*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).

What treatments are available?

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

How is this medicine expected to work?

This medicine blocks a receptor called ‘complement 5a receptor’ (C5aR), which is normally activated by C5a, one of a group of proteins (‘the complement system’) that is involved in inflammation. When C5a attaches to C5aR found in brain cells, it attracts and activates certain inflammatory cells, leading to inflammation in the brain. It is thought that in people with ALS brain cells contain high amounts of C5aR. By blocking C5aR, the medicine is expected to reduce inflammation of the brain, thus improving the symptoms of the disease.

What is the stage of development of this medicine?

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 ALS had been started.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 June 2015 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.