EU/3/16/1627: Orphan designation for the treatment of post-transplantation lymphoproliferative disorders

A post-transplant lymphoproliferative disorder is a blood cancer (lymphoma) that occurs after transplantation. Following a transplant, patients receive medicines that weaken their immune system (the body's natural defences) to prevent rejection of the transplant. However, a weakened immune system also makes patients vulnerable to infection with viruses such as the Epstein-Barr virus. The Epstein-Barr virus infects white blood cells called B cells and after transplantation it may cause changes to the infected blood cells leading to cancer.

Post-transplant lymphoproliferative disorder is a life-threatening condition and is debilitating due to weight loss, fever and organ dysfunction.

At the time of designation, post-transplant lymphoproliferative disorder affected approximately 1.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 82,000 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 513,700,000 (Eurostat 2016).

At the time of designation, no satisfactory method were authorised in the European Union for the treatment of post-transplant lymphoproliferative disorder. Patients with the condition were treated with medicines authorised for non-Hodgkin's lymphoma.

This medicine is made of cells of the immune system called T cells that have been taken from a donor. The T cells are first mixed with B cells from the same donor that have been infected with the Epstein-Barr virus so that the T cells learn to recognise infected B cells as 'foreign'. The T cells are then grown to increase their numbers. When the medicine is then given to the patient, the T cells are expected to attack and kill the patient's own infected B cells, helping to control cancers associated with the virus.

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 with post-transplant lymphoproliferative disorder were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for post-transplant lymphoproliferative disorder 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 18 February 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.