EU/3/13/1148 - orphan designation for treatment of amyotrophic lateral sclerosis

autologous bone-marrow-derived mesenchymal stromal cells secreting neurotrophic factors

Overview

On 17 July 2013, orphan designation (EU/3/13/1148) was granted by the European Commission to Brainstorm Cell Therapeutics UK Ltd, United Kingdom, for autologous bone-marrow-derived mesenchymal stromal cells secreting neurotrophic factors for the treatment of amyotrophic lateral sclerosis.

The sponsorship was transferred to Brainstorm Cell Therapeutics Limited, Ireland in November 2019.

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. This causes 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 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 35,000 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).

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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 27), Norway, Iceland and Liechtenstein. This represents a population of 509,000,000 (Eurostat 2013).

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 autologous bone-marrow-derived mesenchymal stromal cells secreting neurotrophic factors might be of significant benefit for patients with ALS because early studies show that it might slow the progression of certain symptoms, as observed during the six months following treatment. 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?

The exact cause of the damage to nerves cells in ALS is unknown, but a possible cause could be the impairment of neurotrophic factors. Neurotrophic factors are proteins released by cells in the body that support the survival and development of nerve cells.

The medicine is developed from mesenchymal stromal cells (stem cells) isolated from the patient's own bone marrow. Stem cells can develop into different types of cell. When outside the body, the stem cells are manipulated so that they develop into cells that secrete neurotrophic factors. When transplanted back into the patient, they are expected to secrete neurotrophic factors which will reduce nerve damage and thereby improve 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, 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 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 13 June 2013 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.

EU/3/13/1148: Public summary of opinion on orphan designation: Autologous bone-marrow-derived mesenchymal stromal cells secreting neurotrophic factors for the treatment of amyotrophic lateral sclerosis

Adopted Reference Number: EMA/COMP/417227/2013

Key facts

• Active substance:
  autologous bone-marrow-derived mesenchymal stromal cells secreting neurotrophic factors
• Intended use:
  Treatment of amyotrophic lateral sclerosis
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/13/1148
• Date of designation:
  17/07/2013
• Sponsor:

  Brainstorm Cell Therapeutics Limited; Unit 3d North Point House ; North Point Business Park; New Mallow Road; Cork ; Co. Cork; Ireland; Tel: [phone]; E-mail: [e-mail]

Review of designation

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