EU/3/00/011: Orphan designation for the conditioning treatment prior to 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.

At the time of designation, haematopoietic-progenitor-cell transplantation affected 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 27,000 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. At the time of designation, this represented a population of 378,800,000 (Eurostat 2001).

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.

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.

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 had been granted in the United States for preparative therapy in the treatment of malignancies with bone-marrow transplantation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 27 October 2000 recommending the granting of this designation.

Update: busulfan (Busilvex) has been authorised in the EU since 9 July 2003 for 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.

• 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.