EU/3/16/1652

On 28 April 2016, orphan designation (EU/3/16/1652) was granted by the European Commission to Herantis Pharma Plc, Finland, for recombinant human cerebral dopamine neurotrophic factor 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 certain 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 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 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 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, riluzole was authorised in the EU for the treatment of patients with 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 improve muscle function, when compared with similar early studies of the currently authorised medicine. 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 is made of a protein called cerebral dopamine neurotrophic factor (CDNF). CDNF is thought to play a role in the working of the endoplasmic reticulum, a structure inside cells involved among others in the correct folding of proteins. If this mechanism does not work properly, cells become ‘stressed’ and die. In patients with ALS, this is thought to contribute to the death of the nerve cells that control movement, and thus to the various signs and symptoms of the disease. CDNF is expected to have a protective function in nerve cells, reducing the stress and thus improving the symptoms of the disease.

What is the stage of development of this medicine?

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

At the time of submission, no clinical trials with the medicine in patients with ALS had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for ALS or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 23 March 2016 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.