EU/3/18/2032: Orphan designation for the treatment in haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation (HSCT) is a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells (cells that can develop into different types of cell) from a donor to form new bone marrow that produces healthy blood cells. It can be used to treat serious diseases of the blood and immune system such as leukaemia.

HSCT can be a debilitating and life-threatening procedure due to the risk of severe infections and developing graft-versus-host disease (when the transplanted cells regard the patient's body as 'foreign' and attack the patient's organs, leading to organ damage).

At the time of designation, approximately 0.7 in 10,000 people receive HSCT per year in the European Union (EU). This was equivalent to a total of around 36,000 people per year^*, and is below the ceiling for orphan designation. 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 28), Norway, Iceland and Liechtenstein. This represents a population of 517,400,000 (Eurostat 2018).

At the time of designation, several medicines were authorised in the EU for patients undergoing HSCT. These included radiation treatment or intensive treatment with cancer medicines such as busulfan to clear the bone marrow of existing cells in preparation for HSCT, medicines to help restore the immune system, such as filgrastim, immunoglobulin replacement therapy and Zalmoxis, and medicines to reduce the risk of infections, such as antiviral and antifungal medicines. Medicines that suppress the immune system, such as ciclosporin and corticosteroids, were used for the treatment of graft-versus-host disease.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients undergoing HSCT. Studies indicate that carmustine in combination with other medicines can prepare patients for autologous (from the patient's own body) HSCT leading to better outcomes than other available combinations.This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Carmustine is a cancer medicine that works by preventing cells from multiplying. It is intended to be used with other medicines to prepare the patient for HSCT by clearing the bone marrow of cells.

The effects of carmustine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with carmustine in patients undergoing HSCT were planned.

At the time of submission, carmustine was authorised in several countries in the EU for treatment of various cancers.

At the time of submission, carmustine was not authorised anywhere in the EU for use in patients undergoing HSCT. Orphan designation of carmustine had been granted in the United States for conditioning treatment prior to hematopoietic progenitor cell transplantation.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 24 May 2018 recommending the granting of this designation.

• 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.