EU/3/20/2307: Orphan designation for the treatment of T-cell prolymphocytic leukaemia

T-cell prolymphocytic leukaemia is a cancer of a type of white blood cells, called T cells, which play an important role in the immune system (the body's natural defences).

When leukaemia develops, the bone marrow produces large numbers of abnormal blood cells. In patients with T-cell prolymphocytic leukaemia there is uncontrolled growth of abnormal, immature T cells called prolymphocytes. The prolymphocytes do not work properly, and over a period of time these abnormal cells replace the normal blood cells in the bone marrow and blood. They spread to other organs such as the lymph nodes, liver and spleen, causing enlargement and impairing their function. They also spread to the skin causing rashes, plaques and tumours which can be itchy and painful.

The disease is life-threatening, with poor long-term survival, and chronically debilitating due to its effects on the bone marrow, blood and organs.

At the time of designation, T-cell prolymphocytic leukaemia affected approximately 0.1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 5,000 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 application for orphan designation, no satisfactory treatments had been authorised for the treatment of the condition. Patients were normally given chemotherapy (cancer medicines) in line with the treatment of other leukaemias. Some patients might receive haematopoietic stem cell transplants (a procedure where the patient's bone marrow is cleared of cells and replaced by stem cells to form new bone marrow that produces healthy cells).

This medicine is a compound developed by linking together molecules of two other cancer medicines, bendamustine and vorinostat. Bendamustine belongs to a group of cancer medicines called 'alkylating agents'. It attaches to the DNA of cells while they are reproducing, stopping cell division. As a result, the cancer cells cannot divide and the growth of tumours slows down. The vorinostat part of the molecule controls the switching on and off of genes, and is expected to make it easier for the alkylating agent to access and attach to DNA.

The effects of tinostamustine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with tinostamustine in patients with T-cell prolymphocytic leukaemia had been started.

At the time of submission, tinostamustine was not authorised anywhere in the EU for the treatment of T-cell prolymphocytic leukaemia. Orphan designation of tinostamustine had been granted in the United States for the condition.

In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 18 June 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.