EU/3/16/1797 - orphan designation for treatment of graft-versus-host disease

arsenic trioxide

Overview

On 12 December 2016, orphan designation (EU/3/16/1797) was granted by the European Commission to Medsenic, France, for arsenic trioxide for the treatment of graft-versus-host disease.

The sponsor's address was updated in July 2018.

What is graft-versus-host disease?

Graft-versus-host disease is a complication that can affect patients who have had allogeneic haematopoietic (blood) stem-cell transplantation to treat diseases of the blood such as leukaemia (a cancer of the white blood cells). The procedure involves a patient receiving stem cells from a matched donor to help restore the bone marrow, which produces new blood cells.

Graft-versus-host disease occurs when transplanted cells recognise the patient's body as 'foreign' and attack the patient's organs, such as the stomach, gut, skin and liver, leading to organ damage. The disease may happen shortly after transplantation or later on, in which case a wider range of organs can be involved.

Graft-versus-host disease is a serious and life-threatening disease with a high mortality rate.

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

At the time of designation, graft-versus-host disease affected approximately 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 26,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, several medicines were authorised in the European Union (EU) for the treatment of graft-versus-host disease, such as ciclosporin and corticosteroids. Treatment aimed to reduce the activity of transplanted cells involved in graft-versus-host disease, thereby reducing their ability to attack the patient's organs.

The sponsor has provided sufficient information to show that arsenic trioxide might be of significant benefit for patients with graft-versus-host disease because laboratory studies suggest that it might improve the outcome of patients with this condition when used together with ciclosporin. 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?

Arsenic trioxide is a chemical that has been used in medicines for many years and is currently authorised in the EU for the treatment of leukaemia. In graft-versus-host disease, arsenic trioxide is thought to work by increasing the production of reactive oxygen species (ROS, toxic molecules containing oxygen) to a level where ROS is toxic to the transplanted T cells and causes their death. Since transplanted T cells are involved in graft-versus-host disease, this is expected to improve the symptoms of the condition.

What is the stage of development of this medicine?

The sponsor has provided laboratory data from the published literature to support the application for orphan designation.

At the time of submission of the application for orphan designation, no clinical trials with arsenic trioxide in patients with graft-versus-host disease had been started.

At the time of submission, arsenic trioxide was not authorised anywhere in the EU for graft-versus-host disease 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 4 November 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.

EU/3/16/1797: Public summary of opinion on orphan designation: Arsenic trioxide for the treatment of graft-versus-host disease

Adopted Reference Number: EMA/744548/2016

Key facts

• Active substance:
  arsenic trioxide
• Intended use:
  Treatment of graft-versus-host disease
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/16/1797
• Date of designation:
  12/12/2016
• Sponsor:

  Medsenic; 204 avenue de Colmar; 67100 Strasbourg; France; 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.