EU/3/19/2138: Orphan designation for the treatment of post-transplant lymphoproliferative disorder

Post-transplant lymphoproliferative disorder is a group of disorders that cause rapid growth of a type of white blood cell called B cells 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 is a common virus which can infect B cells. After transplantation, the virus 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 0.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 41,000 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, various cancer medicines were authorised in the EU for the treatment of lymphomas in patients with post-transplant lymphoproliferative disorder.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with post-transplant lymphoproliferative disorder. Early studies showed that patients whose condition did not respond to standard treatments responded completely to this medicine and had improved survival. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine contains certain cells of the immune system called cytotoxic T cells, which kill infected or abnormal cells. To make this medicine, cytotoxic T cells obtained from healthy donors are exposed to protein fragments from the Epstein-Barr virus, so that they can recognise B cells infected with the virus and attack them. When the medicine is 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, a clinical trial with the medicine in patients with post-transplant lymphoproliferative disorder had finished.
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 24 January 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.