EU/3/05/293

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Orphan designation

On 16 June 2005, orphan designation (EU/3/05/293) was granted by the European Commission to GlaxoSmithKline Research & Development Limited, United Kingdom, for nelarabine for the treatment of acute lymphoblastic leukaemia. The sponsorship was transferred to Glaxo Group Limited, United Kingdom, in August 2006.

What is acute lymphoblastic leukaemia?

Acute lymphoblastic leukaemia is a disease in which cancer cells are found in the blood and the bone marrow. The bone marrow is the spongy tissue inside the large bones in the body. Normally, the bone marrow makes cells called “blasts” that mature into several different types of blood cells that have specific functions in the body. These include red cells, white cells and platelets. Red blood cells carry oxygen and other materials to all tissues of the body. White blood cells fight infection. Platelets make the blood clot. When leukaemia develops, the bone marrow produces large numbers of abnormal blood cells. There are several types of leukaemias. Acute lymphoblastic leukaemia is a cancer of certain white blood cells called lymphocytes. In this disease the lymphocytes multiply too quickly and live too long, so there are too many of them circulating in the blood. These leukaemic lymphocytes look normal, but they are not fully developed and do not work properly. Over a period of time these abnormal cells replace the normal white cells, red cells and platelets in the bone marrow. It is the most common type of leukaemia in young children. This disease also affects adults, especially those aged 65 and older. Many people with acute leukaemia can be cured. However, despite the available treatments, acute lymphoblastic leukaemia remains a serious and life threatening condition in a subgroup of patients.

What are the methods of treatment available?

Treatment for leukaemia is complex and depends on a number of factors including the type of leukaemia, the extent of the disease and whether the leukaemia has been treated before. It also depends on the patient's age, symptoms, and general health. The primary treatment of acute lymphoblastic leukaemia is chemotherapy (using drugs to kill cancer cells) followed or combined with radiotherapy (using high-energy x-rays or other types of high-energy rays to kill cancer cells). Bone marrow transplantation is also available.
Satisfactory argumentation has been submitted by the sponsor to justify the assumption that nelarabine might be of potential significant benefit for the treatment of acute lymphoblastic leukaemia mainly because it might improve the long-term outcome of the patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain orphan status.

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

Based on the information provided by the sponsor and previous knowledge of the Committee, acute lymphoblastic leukaemia was considered to affect approximately 1.1 in 10,000 persons in the European Union, which, at the time of designation, corresponded to about 51,000 persons.

*Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

Enzymes are proteins produced by the human body that speed up the conversion of certain substances into other substances. Once in the blood, an enzyme naturally present in the body, converts nelarabine in a substance called arabinofuranosylguanine (ara-G). Ara-G is incorporated in the human genetic material (DNA) of the cancer cell and might lead to induce the so-called programmed cell death (apoptosis), which is an important process for the natural death of cells. Thus, it is believed that nelarabine could trigger cancer cell death in patients with acute lymphoblastic leukaemia.

What is the stage of development of this medicinal product?

The effects of nelarabine were evaluated in experimental models.

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

Nelarabine was not marketed anywhere worldwide for acute lymphoblastic leukaemia, at the time of submission. Orphan designation of acute lymphoblastic leukaemia was granted in the United States for treatment of acute lymphoblastic leukaemia and lymphoblastic lymphoma.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 12 May 2005 a positive opinion recommending the grant of the above-mentioned designation.

Update: Nelarabine (Atriance) is authorised in the European Union as of 22 August 2007 for the treatment of patients with T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens. Due to the small patient populations in these disease settings, the information to support these indications is based on limited data.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:
  • the seriousness of the condition, 
  • the existence or not of alternative methods of diagnosis, prevention or treatment and 
  • either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for 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 will be necessary before this product can be granted a marketing authorisation.

Key facts

Product details for <p>Nelarabine</p>
Active substanceNelarabine
Medicine NameAtriance
Disease/conditionTreatment of acute lymphoblastic leukaemia
Date of decision16/06/2005
OutcomePositive
Orphan decision numberEU/3/05/293

Review of designation

Related information

Sponsor’s contact details:

Glaxo Group Limited
Glaxo Wellcome House
Berkely Avenue
Greenford
Middlesex UB6 0NN
United Kingdom
Telephone: +44 20 84 22 34 34
Telefax: +44 20 84 23 44 01

Patients’ associations contact points:

Leukaemia Care
2 Shrubbery Avenue
Worcester
WR1 1QH
United Kingdom
Telephone: +44 19 05 33 00 03
Telefax: +44 19 05 33 00 90
E-mail: info@leukaemiacare.org.uk

Associazione Italiana contro le Leucemie-linfomi e mieloma ONLUS
Via Ravenna, 34
00161 Roma
Italy
Telephone : +39 06 44 03 763
Telefax : +39 06 44 04 226
E-mail: ail@ail.it

Ligue Nationale Contre le Cancer
13 Av. de la Grande Armee
75116 Paris
France
Telephone: +33 1 45 00 00 17
Tefefax: +33 1 45 00 63 06
E-mail: ligue@ligue-cancer.net