EU/3/20/2327 - orphan designation for treatment of diffuse large B-cell lymphoma
autologous T cells transduced with lentiviral vector containing a tandem chimeric antigen receptor directed against CD20 and CD19
OrphanHuman
Overview
On 21 August 2020, orphan designation EU/3/20/2327 was granted by the European Commission to Miltenyi Biomedicine GmbH, Germany, for autologous T cells transduced with lentiviral vector containing a tandem chimeric antigen receptor directed against CD20 and CD19 (also known as MB-CART2019.1) for the treatment of diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma is a type of blood cancer and the most common form of a group of blood cancers known as non-Hodgkin lymphomas.
Diffuse large B-cell lymphoma affects a type of white blood cells called B lymphocytes, or B cells. In patients with this cancer, the B cells multiply quickly and live for too long, so there are too many of them in the lymph nodes. The first sign of the disease is usually a lump in the neck, under the arm or in the groin area, which is caused by an enlarged lymph node. Patients with diffuse large B-cell lymphoma may also have fever, tiredness, night sweats or weight loss that have no obvious cause.
Although some people with diffuse large B-cell lymphoma can be cured, it remains a serious and life-threatening disease, particularly when the disease is diagnosed late or has come back after treatment.
At the time of designation, diffuse large B cell lymphoma affected approximately 4.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 234,000 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 designation, several medicines were authorised for the treatment of diffuse large B-cell lymphoma in the EU. The main treatment was chemotherapy (medicines to treat cancer) usually in combination with medicines called monoclonal antibodies and sometimes with radiotherapy (treatment with radiation). The gene therapy medicines axicabtagene ciloleucel and tisagenlecleucel, also called CAR-T cells, were used when other cancer medicines had not worked.
Autologous haematopoietic (blood) stem-cell transplantation was also used in patients at risk of the disease coming back after treatment. This procedure involves replacing the patient's bone marrow with the patient's own stem cells to form new bone marrow that produces healthy blood cells.
The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with diffuse large B cell lymphoma because laboratory results suggest that the way the medicine works by targeting 2 proteins could provide better results than CAR-T cell medicines that have one target. In addition, early results in patients whose cancer did not respond to previous treatments or had come back indicate that they may benefit from treatment with the medicine. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The cancer cells in patients with diffuse large B cell lymphoma produce proteins on their surface called CD19 and CD20.
The medicine is made from the patient’s own T cells. T cells are cells of the immune system (the body's natural defences) that can kill cancer cells. The T cells have been modified in the laboratory by a virus that carries a gene into the cells, enabling them to produce a receptor that targets CD19 and CD20. When given back to the patient, with this receptor on their surface the modified cells, called CAR-T cells, are expected to attach to CD19 and CD 20 on the cancer cells and kill them, thus reducing the growth and spread of the tumour.
The virus used in this medicine ('lentivirus') is modified so that it does not 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 diffuse large B cell lymphoma were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for the treatment of diffuse large B cell lymphoma or designated as an orphan medicinal product elsewhere for this condition.
In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 16 July 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.
Key facts
- Active substance
- autologous T cells transduced with lentiviral vector containing a tandem chimeric antigen receptor directed against CD20 and CD19
- Intended use
- Treatment of diffuse large B-cell lymphoma
- Orphan designation status
- Positive
- EU designation number
- EU/3/20/2327
- Date of designation
- Sponsor
Miltenyi Biotec GmbH
Friedrich-Ebert-Str. 68
Moitzfeld
51429 Bergisch Gladbach
Germany
Tel. +49 22048306820
E-mail: biomedicine@miltenyi.com
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
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.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: