EU/3/19/2211: 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). Additionally, in some patients the stem cells do not establish themselves and succeed in forming new bone marrow.

At the time of designation, approximately 0.80 in 10,000 people in the European Union (EU) had received haematopoietic stem cell transplantation. This was equivalent to a total of around 40,000 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 (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 518,400,000 (Eurostat 2019).

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, medicines to help restore the immune system, such as filgrastim and 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 the medicine might be of significant benefit for patients undergoing haematopoietic stem cell transplantation because early results in patients suggested that when added to standard medicines to clear the bone marrow the medicine increased the likelihood that the HSCT procedure would be successful.

This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

In order for new stem cells to successfully establish themselves, the patient’s existing bone marrow needs to be cleared using radiation treatment or medicines to destroy the existing bone marrow. Besilesomab is a monoclonal antibody (a type of protein) that targets CD66 proteins found on the surface of bone marrow cells, linked to a component that can carry a radioactive element. When the medicine is loaded with a radioactive substance called yttrium ⁹⁰Y and given to the patient it attaches to the bone marrow cells, which are then selectively killed by the radiation from the yttrium. This is expected to improve clearance of the old bone marrow and increase the chances for successful HSCT.

The effects of besilesomab have been evaluated in experimental models.

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

At the time of submission, besilesomab 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, the COMP adopted a positive opinion on 12 September 2019, 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.