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Orphan designation

On 22 May 2006, orphan designation (EU/3/06/374) was granted by the European Commission to Johnson & Johnson Medical Ltd, United Kingdom, for methoxsalen for the treatment of graft-versus-host disease.

The sponsorship was transferred to Therakos (UK) Limited, United Kingdom, in September 2013.

What is graft-versus-host disease?

Graft-versus-host disease (GvHD) is a complication of bone-marrow transplant. The bone marrow is the spongy tissue inside the large bones in the body that makes blood cells and platelets (components that help the blood to clot). Bone-marrow transplants are used for diseases such as leukaemia or multiple myeloma (cancer of the white blood cells).

In GvHD, the cells in the transplanted bone marrow react against the patients’ organs, such as the stomach, gut, skin and liver, leading to organ damage. GvHD may happen in the short term, or later after transplantation, in which case a wider range of organs can be involved. GvHD is a serious, life-threatening disease.

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

At the time of designation, GvHD affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 47,000 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 affected by the condition is estimated and assessed on the basis of data from the European Union (EU 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 468,900,000 (Eurostat 2006).

What treatments are available?

The methods of treatment authorised for GvHD in the Community, at the time of submission of the application for orphan designation, included anti-T-cell immunoglobulins (proteins called antibodies that block the effect of T cells of the immune system) and ciclosporin (an immunosuppressant). In addition, systemic corticosteroids (synthetic steroid hormones administered so that they can affect the body as a whole) are usually administered at high doses. Other therapies include various immunosuppressants (drugs that inhibit the immune response). Satisfactory argumentation has been submitted by the sponsor to justify the assumption that the medicinal product might be of potential significant benefit for the treatment of GvHD, particularly in terms of improved efficacy and limiting drug toxicity (steroid-sparing effect).

How is this medicine expected to work?

Methoxsalen is pharmacologically active only when exposed to ultraviolet light and it has been proposed for use in conjunction with a method called extracorporeal photopheresis (ECP) for treatment of GvHD. Briefly, the ECP procedure involves chemical treatment of graft cells (cells that will be inserted to the body) with a drug that is activated by light (e.g. methoxsalen), exposing this mix to ultraviolet light and returned to the patient. Methoxsalen is thought to bind to the genetic material (DNA helix) of graft-reactive cells and block their division and growth. The exact mechanisms by which ECP and methoxsalen can lead to improvement in GvHD have not been fully clarified. ECP may be involved in enhancing the apoptotic process (a form of programmed cell death) which might destroy graft-reactive T cells. Another possibility is that the photoactivated methoxsalen might trigger the induction of specific T cells able to suppress the immune response against the host tissues.

What is the stage of development of this medicine?

The effects of methoxsalen were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with GvHD were ongoing.

Methoxsalen was not authorised anywhere worldwide for GvHD at the time of submission. Orphan designation of methoxsalen was granted in the United States for GvHD.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 April 2006 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;
  • and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.

Key facts

Product details for <p>Methoxsalen</p>
Active substanceMethoxsalen
Medicine Name
Disease/conditionTreatment of graft-versus-host disease
Date of decision22/05/2006
Orphan decision numberEU/3/06/374

Review of designation

Sponsor’s contact details

Therakos (UK) Limited
3 Lotus Park
The Causeway
Surrey TW18 3AG
United Kingdom
Tel. +44 (0)1784 636700

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.