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Orphan designation

Please note that this product was withdrawn from the Community Register of designated Orphan Medicinal Products in December 2017 on request of the sponsor.

On 14 December 2015, orphan designation (EU/3/15/1583) was granted by the European Commission to Novartis Europharm Limited, United Kingdom, for 2-amino-2-[2-[2-chloro-4-[[3-(phenylmethoxy)phenyl]thio]phenyl]ethyl]-1,3-propanediol hydrochloride for the prevention of graft-versus-host disease.

What is graft-versus-host disease?

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

In GvHD, the transplanted white blood cells recognise the patient as ‘foreign’ and attack the patient’s organs, such as the stomach, gut, skin and liver, leading to organ damage. GvHD may happen shortly after transplantation or later on, in which case a wider range of organs can be involved.

GvHD is a serious and life-threatening disease with a high mortality rate.

What is the estimated number of patients at risk of developing the condition?

At the time of designation, the number of patients at risk of GvHD was estimated to be less than 1 people in 10,000 in the European Union (EU). This was equivalent to a total of fewer than 51,000 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).

* Disclaimer: For the purpose of the designation, the number of patients at risk of developing 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 methods of prevention are available?

At the time of designation, several medicines were authorised in the EU for the prevention of GvHD, such as cyclosporine and antilymphocyte immunoglobulins (ATG). Treatment aimed to reduce the activity of immune cells involved in GvHD, thereby reducing their ability to attack the patient’s organs.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients at risk of GvHD because initial studies suggest that it may improve the outcome of these patients. 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?

In GvHD, donor white blood cells migrate to host’s immune tissue (such as the thymus and lymph nodes), where they are activated and then released to attack cells throughout the body. Their release is triggered by a substance called sphingosine-1-phosphate, which attaches to so-called S1P1 receptors on the cells. This medicine acts by preventing activation of S1P1 receptors and so keeping most of the donor’s white blood cells in the immune tissue where they cannot attack the cells of the body. This is expected to prevent GvHD.

What is the stage of development of this medicine?

The effects of this 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 at risk of GvHD were ongoing.

At the time of submission, this medicine was not authorised anywhere in the EU for prevention of GvHD 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 12 November 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.

Key facts

Product details for <p>2-amino-2-[2-[2-chloro-4-[[3-(phenylmethoxy)phenyl]thio]phenyl]ethyl]-1,3-propanediol hydrochloride</p>
Active substance2-amino-2-[2-[2-chloro-4-[[3-(phenylmethoxy)phenyl]thio]phenyl]ethyl]-1,3-propanediol hydrochloride
Medicine Name
Disease/conditionPrevention of graft-versus-host disease
Date of decision14/12/2015
Orphan decision numberEU/3/15/1583

Review of designation

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

Sponsor’s contact details

Novartis Europharm Limited
Frimley Business Park
Camberley GU16 7SR
United Kingdom
Tel. +41 6132 41111

Patients’ organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.