On 29 April 2014, orphan designation (EU/3/14/1266) was granted by the European Commission to Novartis Europharm Limited, United Kingdom, for autologous T cells transduced with lentiviral vector containing a chimeric antigen receptor directed against CD19 for the treatment of B-lymphoblastic leukaemia/lymphoma.
The sponsorship was transferred to Novartis Europharm Limited, Ireland, in May 2018.
This medicine is now known as tisagenlecleucel.
Autologous T cells transduced with lentiviral vector containing a chimeric antigen receptor directed against CD19 for treatment of B-lymphoblastic leukaemia/lymphoma has been authorised in the EU as Kymriah since 23 August 2018.
B-lymphoblastic leukaemia/lymphoma is a cancer of the white blood cells called B lymphocytes or B cells, which multiply too quickly and live for too long so there are too many of them circulating in the blood. These abnormal B cells 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 bone marrow (the spongy tissue inside the large bones in the body, where blood cells are produced).
B-lymphoblastic leukaemia/lymphoma is a long-term debilitating and life-threatening disease because the abnormal immature cells take the place of the normal white blood cells, reducing the patient's ability to fight infections and causing organ damage.
At the time of designation, B-lymphoblastic leukaemia/lymphoma affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 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. At the time of designation, this represented a population of 512,900,000 (Eurostat 2014).
Treatment for B-lymphoblastic leukaemia/lymphoma 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, treatment for B-lymphoblastic leukaemia/lymphoma included chemotherapy (medicines to treat cancer) that may be followed by or combined with radiotherapy (treatment with radiation). Haematopoietic (blood) stem-cell transplantation 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 the medicine might be of significant benefit for patients with B-lymphoblastic leukaemia/lymphoma because early studies in patients indicate that it might benefit patients whose disease does not respond to standard treatments, or has come back after treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The abnormal B cells in patients with B-lymphoblastic leukaemia/lymphoma produce a protein on their surface called CD19. To make this medicine, T cells (a different type of white blood cell that is part of the body's natural defences) are taken from the patient and modified in the laboratory by a virus that carries a gene into the cells which allows them to target CD19. The modified T cells are grown to increase their numbers before being given back to the patient. Once the modified T cells are returned to the patient, they are expected to attach to CD19 of the cancer cells and kill them.
The type of virus used in this medicine ('lentivirus') is modified in order not to cause disease in humans.
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 B-lymphoblastic leukaemia/lymphoma were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for B-lymphoblastic leukaemia/lymphoma. Orphan designation of the medicine had been granted in the United States for the treatment of acute lymphoblastic leukaemia.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 March 2014 recommending the granting of this designation.
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.
Novartis Europharm Limited
The Committee for Orphan Medicinal Products reviewed the orphan designation of Kymriah at the time of marketing authorisation, and confirmed that the orphan designation should be maintained.
More information is available in the Kymriah : Orphan maintenance assessment report (initial authorisation).
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: