EU/3/20/2260: 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 cells 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 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 1 in 10,000 people received HSCT every year in the European Union (EU). This was equivalent to a total of around 52,000 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).

*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, Iceland, Liechtenstein, Norway and the United Kingdom. This represents a population of 519,200,000 (Eurostat 2020).

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, 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. Early studies show that it can improve the condition of patients with viral haemorrhagic cystitis (an infection of the bladder), which is a complication of HSCT.

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

Patients undergo HSCT to replace their bone marrow cells, which include the white blood cells (called T cells) that fight infection. Before the new bone marrow cells are fully functional, the patients are therefore at risk of infections, such as viral haemorrhagic cystitis.

This medicine is made up of white blood cells from a donor which have been activated to target viruses that can cause viral haemorrhagic cystitis and other serious viral infections in patients who have undergone HSCT. When these white blood cells are injected into the patients, they are expected to provide protection against these viruses while the patient’s immune system is being restored.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients who had viral haemorrhagic cystitis after undergoing 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, the COMP adopted a positive opinion on 20 February 2020, 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.