EU/3/06/420: Orphan designation for the treatment of mantle cell lymphoma

Mantle cell lymphoma belongs to the group of diseases called “non-Hodgkin lymphomas”. Lymphoma is a type of cancer that originates from the lymphatic system. The lymphatic system is part of the immune system: the body's natural defence against infection and disease. It is a complex system made up of organs such as the bone marrow (the spongy tissue inside the large bones in the body), the thymus and the spleen, and a network of lymph nodes throughout the body that are connected by lymphatic vessels. Normally, the lymphatic cells grow in a controlled manner. However, in lymphoma a lymphatic cell continues to grow and divides in an uncontrolled manner, developing into a tumour. Lymphoma cells generally grow in lymph nodes. There are several different types of lymphoma depending on the type of lymphatic cancer cells. In mantle cell lymphoma, the cancer cells are related to the blood cells called B-lymphocytes. Mantle cell lymphoma is a life-threatening condition.

At the time of designation mantle cell lymphoma affected approximately 0.4 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 18,000 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 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 459,700,000 (Eurostat 2004).

Treatment of mantle cell lymphoma includes chemotherapy (using drugs to kill cancer cells), radiotherapy (using high-dose x-rays or other high-energy rays to kill cancer cells) and immunotherapy (using drugs that stimulate the body's own immune system to kill the cancer cells). There are currently several medicinal products authorised in the Community for treatment of non-Hodgkin lymphomas. The choice of treatment depends in particular on the stage of the disease as well as on the responses to therapies previously prescribed.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that temsirolimus might be of potential significant benefit for the treatment of mantle cell lymphoma, mainly because it may work for patients where other treatments have failed. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Temsirolimus is designed to inhibit (block) the enzyme (a protein that triggers chemical reactions in the body) called serine/threonine kinase. This enzyme plays a role in a cascade of molecular reactions involved in the control of growth and division of cells. In cancer cells, the function of this enzyme is disturbed causing uncontrolled growth and too much division of the cancer cells, making them develop into tumours. According to the sponsor, temsirolimus might, by inhibition of the activity of serine/threonine kinase, help in slowing down or stopping the further growth of cancer cells.Describe as simply as possible the clinically relevant principal mechanism of action and try to link this to the condition applied for.

The effects of temsirolimus were evaluated in experimental models.

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

Temsirolimus was not authorised anywhere worldwide for the treatment of mantle cell lymphoma, at the time of submission. Orphan designation of temsirolimus was granted in the European Union for the treatment of renal cell carcinoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 4 October 2006 recommending the granting of this designation.

Update: temsirolimus (Torisel) has been authorised in the EU since 21 August 2009 for the treatment of adult patients with relapsed and/or refractory mantle cell lymphoma [MCL].

• 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 European Union) 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.