EU/3/00/011

On 29 December 2001, orphan designation (EU/3/00/011) was granted by the European Commission to Pierre Fabre Médicament, France, for busulfan (intravenous use) for the conditioning treatment prior to haematopoietic progenitor cell transplantation.

What is haematopoietic progenitor cell transplantation?

The term “progenitor cell” is used to indicate those cells that are still immature, and do not express all the characteristics of the future mature cells that will be derived from them. Haematopoietic progenitor cells are able to produce the cells of the blood (white blood cells, red blood cells), including the cells of the immune system and of the bone marrow. In some diseases it is necessary to give powerful drugs, which also destroy the haematopoietic progenitor cells in the bone marrow; these bone marrow cells then need to be replaced. In other diseases, the bone marrow or the immune system are absent, or working abnormally. In all these cases, it is sometimes appropriate to use a treatment called “haematopoietic progenitor cell transplantation”. This includes replacing the abnormal cells of the immune system and the bone marrow of the patient by introducing new progenitor cells, generally from another person. Before the transplantation can take place, any existing bone marrow cells have to be eliminated from the patient. This is called “preparation” treatment or “conditioning” treatment. Diseases requiring such transplantation are life-threatening.

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

At the time of designation haematopoietic progenitor cell transplantation affected 0.7 in 10,000 people in the European Union (EU)*. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 26,000 people.

*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. This represents a population of 377,000,000 (Eurostat 2001).

What treatments are available?

Several chemotherapeutic medicinal products (drugs that kill cancer cells) and irradiation methods (using high energy rays) were authorised for the conditioning treatment prior to haematopoietic progenitor cell transplantation.

Satisfactory argumentation has been submitted by the sponsor to justify the assumption that busulfan might be of potential significant benefit for the conditioning treatment prior to haematopoietic progenitor cell transplantation. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

Busulfan is a so-called alkylating chemotherapeutic agent. It acts by damaging DNA (the genetic material found in every cell) in cells that are rapidly dividing such as cancer cells. This leads to the destruction of the cancer cells.

What is the stage of development of this medicine?

The effects of busulfan were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with haematopoietic progenitor cell transplantation were ongoing.

Busulfan was authorised in several countries worldwide for the indicated condition and similar conditions, at the time of submission. Orphan designation of busulfan was granted in the United States for preparative therapy in the treatment of malignancies with bone marrow transplantation.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 27 October 2000 a positive opinion recommending the grant of the above-mentioned designation.

Update: Busulfan (Busilvex) has been authorised in the EU since 9 July 2003. Busilvex followed by cyclophosphamide (BuCy2) is indicated as conditioning treatment prior to conventional haematopoietic progenitor cell transplantation (HPCT) in adult patients when the combination is considered the best available option. Busilvex followed by cyclophosphamide (BuCy4) or melphalan (BuMel) is indicated as conditioning treatment prior to conventional haematopoietic progenitor cell transplantation in paediatric patients.

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;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.