EU/3/16/1760 - orphan designation for 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 such as leukaemia. Before receiving the transplant, the patient's own bone marrow is cleared of cells. The patient then receives 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) receive 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. 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 (European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

At the time of designation, several treatments were available 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.

The sponsor has provided sufficient information to show that radio-iodinated (¹³¹I) anti-CD45 murine monoclonal antibody might be of significant benefit for patients receiving haematopoietic stem cell transplantation. Preliminary studies in patients with leukaemia that had come back or not responded to treatment, and who were not suitable for intensive treatments to clear the bone marrow, suggested that adding this medicine to conventional treatments before a transplant might improve how long such patients live. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is made of a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a receptor called CD45 found only on the surface of white blood cells and on the stem cells in the bone marrow that make them. The antibody is attached to a molecule containing a form of iodine, ¹³¹I, that emits low-level radiation. When the medicine is given, the antibody attaches to these cells in the bone marrow, so the radiation can kill them without affecting other tissues elsewhere in the body. This clears the bone marrow so that donor stem cells can be given as a transplant.

The effects of this 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 requiring treatment in haematopoietic stem cell transplantation were ongoing.

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

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 September 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.