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Orphan designation

On 9 August 2012, orphan designation (EU/3/12/1039) was granted by the European Commission to AOP Orphan Pharmaceuticals AG, Austria, for recombinant anti-CD3-bi-single-chain-Fv-diphtheria toxin fusion protein for the treatment of cutaneous T-cell lymphoma.

What is cutaneous T-cell lymphoma?

Cutaneous T-cell lymphoma (CTCL) is a cancer of the lymphatic system, a network of vessels that transport fluid from tissues through the lymph nodes and into the bloodstream. In CTCL there is uncontrolled growth of the T lymphocytes (T cells), a type of white blood cell found in the lymphatic system. The cancerous T cells appear in the skin, causing lesions (rashes, plaques and tumours) which can be itchy and painful.

CTCL usually happens in people aged between 40 and 60 years. In many cases, the disease is long lasting, however, it can be a serious and life-threatening disease because it can develop into more aggressive forms of cancer and may have a large impact on quality of life, particularly because the skin lesions can cause disfigurement.

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

At the time of designation, CTCL affected less than 1 in 10,000 people in the European Union (EU)*. This is 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 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 506,300,000 (Eurostat 2011).

What treatments are available?

At the time of designation, several products were authorised for the treatment of CTCL within the EU. Treatments for CTCL can be divided into topical (applied to the skin) and systemic (affecting the whole body):

  • topical treatments include topical corticosteroids, the topical anticancer medicine carmustine, ultraviolet light and X-rays;
  • systemic treatments include cytotoxic medicines (medicines that kill cells that are dividing, such as cancer cells) and interferon alfa (a medicine that helps the immune system to fight against the cancer cells).

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with CTCL because it works in a different way to existing treatments and early studies suggest it may improve patients’ condition. 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 contains a toxin (a substance toxic for cells) called diphtheria toxin, which has been ‘fused’ to fragments of a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific structure. The monoclonal antibody fragments in this medicine are expected to attach to a protein called CD3, which is found on the surface of certain T cells. The monoclonal antibody fragments carry for the toxin to the CD3-positive T cells, which are found on most CTCLs. Once taken up by the T cells, the toxin is expected to kill the cancer cells.

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 CTCL were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for CTCL 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 11 July 2012 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>Recombinant anti-CD3-bi-single-chain-Fv-diphtheria toxin fusion protein</p>
Active substanceRecombinant anti-CD3-bi-single-chain-Fv-diphtheria toxin fusion protein
Medicine Name
Disease/conditionTreatment of cutaneous T-cell lymphoma
Date of decision09/08/2012
Orphan decision numberEU/3/12/1039

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:

AOP Orphan Pharmaceuticals AG
Wilhelminenstrasse 91/IIf
A-1160 Vienna
Telephone: +43 1 503 72 44 10
Telefax: +43 1 503 72 44 61

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.