EU/3/15/1546: Orphan designation for the treatment of acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) is a cancer of the white blood cells called lymphocytes. In ALL, the lymphocytes multiply too quickly and live for too long so there are too many of them circulating in the blood. These abnormal lymphocytes are not fully developed and do not work properly. Over a period of time, they replace the normal white blood cells, red blood cells and platelets in the bloodstream and the bone marrow (the spongy tissue inside the large bones in the body, where blood cells are produced).

ALL is a debilitating and life-threatening disease because the abnormal immature cells take the place of the normal blood cells, reducing the patient's ability to fight infections and causing organ damage.

At the time of designation, ALL affected approximately 1 in 10,000 people in the European Union (EU). This was equivalent to a total of around 51,000 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 512,900,000 (Eurostat 2015).

Treatment for ALL is complex and depends on a number of factors including the extent of the disease, whether it has been treated before and the patient's age, symptoms and general state of health. At the time of designation, the main treatment for ALL was chemotherapy (medicines to treat cancer) followed by or combined with radiotherapy (treatment with radiation). Haematopoietic (blood) stem-cell transplantation (HSCT) was also used. This is a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with ALL because early studies indicate that using the medicine for HSCT may lead to an early recovery of bone marrow function. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is a type of advanced therapy medicine called a 'tissue engineered product'. This is a type of medicine containing cells or tissues that have been manipulated so that they can be used to repair, regenerate or replace tissue.

The medicine is made up of blood cells, including stem cells, from umbilical cord blood that have been treated with a chemical called '16,16-dimethyl prostaglandin E2' (dmPGE2). Stem cells are cells that can develop into different types of cell. The umbilical cord stem cells are used to replace the cells in the patient's bone marrow. Treatment with dmPGE2 is expected to improve the properties of these cells, making them better able to survive, multiply, and settle in the patient's bone marrow.

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 ALL were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for ALL. Orphan designation of the medicine had been granted in the United States for the broad indication 'enhancement of stem cell engraftment through ex vivo treatment of human allogeneic hematopoietic stem cells (treatment of neutropenia, thrombocytopenia, lymphopenia, and anaemia)'.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 16 July 2015 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.