EU/3/16/1674: Orphan designation for the treatment in haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation involves a patient receiving stem cells (cells that can develop into different types of cell) to help the bone marrow produce healthy blood cells. It can be used to treat serious diseases of the blood and immune system. A stem cell transplant in which the patient receives cells from a healthy donor is called an allogeneic transplant. Before receiving the transplant, the patient's own bone marrow is cleared of cells. The patient then receives the donor stem cells, which multiply and develop into healthy blood cells.

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*, 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 (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 medicines to help restore the immune system, such as immunoglobulin replacement therapy, and 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 early studies showed that its use resulted in fewer admissions to hospital, less time spent in hospital, fewer infections and improved survival when used on top of standard of care. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

For many patients who require haematopoietic stem cell transplantation, it is often difficult to find a fully matched donor. When the donor is partly matched to the patient (e.g. a close relative), the risk of the patient developing graft-versus-host disease is increased.

This medicine is made of T lymphocytes or T cells, a type of white blood cell, extracted from a donor who is partly matched to the patient. These T cells are genetically modified to include a 'suicide gene'. The patient first receives the transplant which has had the donor's T cells removed. Afterwards the modified T cells are given. The suicide gene in the T cells is switched off. These cells are expected to help the patient to fight off viral infections while their immune system is being restored with the transplanted stem cells.

However, the transplanted T cells can cause graft-versus-host disease. If the patient develops graft-versus-host disease, a medicine called rimiducid is given to switch on the suicide gene in the T cells. This causes the T cells to die, thus preventing further development of the disease.

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. This medicine in combination with rimiducid has been designated as an orphan medicinal product in the United States for 'replacement T-cell therapy for the treatment of immunodeficiency and graft versus host disease after allogeneic hematopoietic stem cell transplant'.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 19 May 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.