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Orphan designation

On 1 October 2010, orphan designation (EU/3/10/787) was granted by the European Commission to Merck Sharp & Dohme Limited, United Kingdom, for (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt for the treatment of mantle-cell lymphoma.

The sponsorship was transferred to Tesaro U.K. Limited, United Kingdom, in December 2012.

What is mantle-cell lymphoma?

Mantle-cell lymphoma is an aggressive cancer of a type of white blood cell called B-lymphocytes, or B cells. In mantle-cell lymphoma, the B cells multiply too quickly and live for too long, so there are too many of them in the lymph nodes. The first sign of the disease is usually a lump in the neck, under the arm or in the groin area, caused by an enlarged lymph node. Patients may also have fever, weight loss, tiredness and night sweats.

Mantle cell lymphoma is usually diagnosed in people aged over 50 years. It is more common in men than women. Mantle-cell lymphoma is a severe and life-threatening disease that is associated with poor overall survival.

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

At the time of designation, mantle-cell lymphoma affected approximately 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of around 20,000 people*, and is below the threshold 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. At the time of designation, this represented a population of 506,300,000 (Eurostat 2010).

What treatments are available?

At the time of designation, temsirolimus was authorised in the EU for the treatment of mantle-cell lymphoma that had come back after previous treatment or has not responded to other treatments. The main treatments for mantle-cell lymphoma included chemotherapy (medicines to treat cancer), immunotherapy (medicines that stimulate the body’s own immune system to kill the cancer cells) and radiotherapy (treatment with radiation). Haematopoietic (blood) stem cell transplantation was also used. This is a complex procedure where patients receive stem cells to help restore the bone marrow.

The sponsor has provided sufficient information to show that the medicine ‘(3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt’ might be of significant benefit for patients with mantle-cell lymphoma because it works in a different way to existing treatments, and early studies in experimental models indicate that it might be used in combination with existing treatment to improve the outcome of patients with this 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 is expected to work by blocking the enzymes known as poly(ADP-ribose) polymerase (PARP)-1 and -2. These enzymes are used to repair damaged DNA. By blocking PARP-1 and -2, the medicine prevents cancer cells from repairing their DNA, eventually killing them. It is expected that the medicine will be able to be used on its own in some patients with mantle cell lymphoma whose cancer cells do not have other ways of repairing DNA damage. The medicine is also expected to be used in combination with other cytotoxic (cell-killing) medicines that cause DNA damage, where it is expected to make them more effective by preventing DNA repair.

What is the stage of development of this medicine?

The effects of (3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with this medicine in patients with mantle cell lymphoma were planned.

At the time of submission, this medicine was not authorised anywhere in the EU for mantle 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 16 July 2010 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>(3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt</p>
Active substance(3S)-3-{4-[7-(aminocarbonyl)-2H-indazol-2-yl] phenyl} piperidine tosylate monohydrate salt
Medicine Name
Disease/conditionTreatment of mantle-cell lymphoma
Date of decision01/10/2010
Orphan decision numberEU/3/10/787

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

Tesaro U.K. Limited
c/o Sisec Limited
21 Holborn Viaduct
London EC1A 2DY
United Kingdom
Tel. +44 (0)2033 000105
Fax +44 (0)2033 000105

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.