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Orphan designation

On 9 August 2012, orphan designation (EU/3/12/1038) 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 peripheral T-cell lymphoma (nodal, other extranodal and leukaemic / disseminated).

What is peripheral T-cell lymphoma?

Peripheral T-cell lymphoma 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 peripheral T-cell lymphoma there is uncontrolled growth of T lymphocytes (T cells), a type of white blood cell found in the lymphatic system, which appear in the blood circulating in peripheral parts of the body. Different types of peripheral T-cell lymphoma have been identified and categorised as nodal, other extranodal and leukaemic / disseminated.

The symptoms of the disease vary according to the type of lymphoma, but the first sign is usually a lump in the neck, under the arm or in the groin area, which is caused by an enlarged lymph node. The lymphoma may also affect other organs in the body such as the bone marrow, liver and the skin.

Peripheral T-cell lymphoma is a serious and life-threatening condition because in most cases the disease comes back within one year after initial treatment and is associated with poor overall survival.

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

At the time of designation, peripheral T-cell lymphoma 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, there were no specific treatments for peripheral T-cell lymphoma, but the disease was treated in the same way as the broader class of lymphomas known as non-Hodgkin’s lymphomas, for which several medicines were authorised in the EU. The main treatment was chemotherapy (medicines to treat cancer), sometimes in combination with radiotherapy (treatment with radiation).

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with peripheral T-cell lymphoma because it works in a different way to existing treatments and early studies in experimental models suggest it may have anti-tumour activity that is specifically targeted to T cells. 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 the toxin to the CD3-positive T cells, which are found on most peripheral T-cell lymphomas. 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 peripheral T-cell lymphoma were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for peripheral T-cell lymphoma 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 peripheral T-cell lymphoma (nodal, other extranodal and leukaemic / disseminated)
Date of decision09/08/2012
Orphan decision numberEU/3/12/1038

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.