EU/3/16/1774: Orphan designation for the treatment in haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation 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) 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.

Haematopoietic stem cell transplantation 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 recognise the patient's body as 'foreign' and attack the patient's organs leading to organ damage).

At the time of designation, approximately 1 in 10,000 people in the European Union (EU) have haematopoietic stem cell transplants per year. This was equivalent to a total of around 51,000 people per year^1>, 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).

¹Disclaimer: 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 (European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

At the time of designation, several medicines were authorised in the EU for patients undergoing haematopoietic stem cell transplants. These included radiation treatment or intensive treatment with cancer medicines such as busulfan to clear the bone marrow of existing cells, medicines to help restore the immune system, such as immunoglobulin replacement therapy, 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 this medicine might be of significant benefit for patients undergoing haematopoietic stem cell transplantation because experimental studies showed that the medicine may reduce graft-versus-host disease and improve success of the transplant and survival. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine consists of white blood cells, including stem cells, extracted from a donor for use as a transplant. These cells are to be given to the patient to form new bone marrow that produces healthy blood cells. Before they are given to the patient, the cells are mixed with medicines (16, 16-dimethyl prostaglandin E2 and dexamethasone) so that the cells produce more of a protein called CXCR4. This improves the ability of the cells to find their way to the bone marrow and start to grow once transplanted. The cells are also less likely to recognise the patient's body as foreign, and fewer cells able to cause graft-versus-host disease are produced.

The effects of the medicine have been evaluated in experimental models.

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

At the time of submission, the medicine was not authorised anywhere in the EU for use in haematopoietic stem cell transplantation or designated as an orphan medicinal product elsewhere.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 6 October 2016 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.