EU/3/15/1552 - orphan designation for treatment of mantle cell lymphoma

autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3-zeta chimeric antigen receptor (axicabtagene ciloleucel)

Overview

This medicine is now known as axicabtagene ciloleucel.

On 9 October 2015, orphan designation (EU/3/15/1552) was granted by the European Commission to Kite Pharma UK Ltd, United Kingdom, for autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3-zeta chimeric antigen receptor for the treatment of mantle cell lymphoma.

The sponsorship was transferred to Kite Pharma EU B.V., Netherlands, in April 2017. The sponsor’s address was updated in September 2021.

Please note that this product was withdrawn from the Union Register of orphan medicinal products in December 2021 on request of the Sponsor.

What is mantle cell lymphoma?

Mantle cell lymphoma is an aggressive cancer of a type of white blood cell called B lymphocytes, or B cells. In mantle cell lymphoma, the B cells multiply too 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, caused by an enlarged lymph node. Patients may also have fever, weight loss, tiredness and night sweats.

Mantle cell lymphoma is usually diagnosed in people aged over 50 years. It is more common in men than women. Mantle cell lymphoma is a long-term debilitating and life-threatening disease that is associated with poor overall survival.

What is the estimated number of patients affected by the condition?

At the time of designation, mantle cell lymphoma affected less than 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 31,000 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).

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*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).

What treatments are available?

At the time of designation, the main treatments for mantle cell lymphoma included chemotherapy (medicines to treat cancer), immunotherapy (medicines that stimulate the body's own immune system to kill the cancer cells) and radiotherapy (treatment with radiation). Temsirolimus, bortezomib and ibrutinib were specifically authorised in the EU for the treatment of mantle cell lymphoma that has come back after previous treatment or has not responded to other treatments. Haematopoietic (blood) stem-cell transplantation was also used. This is a complex procedure where patients receive stem cells 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 mantle cell lymphoma because early studies show that it might improve the outcome of patients whose disease has come back after previous treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

The abnormal B cells in patients with mantle cell lymphoma produce a protein on their surface called CD19.

This medicine is made up of immune cells (called T cells) which are taken from the patient and modified in the laboratory with a virus that carries a gene into the T cells so that they can recognise and attach to CD19. These modified T cells are then given back to the patient, where they are expected to attach to CD19 on the cancer cells and kill them. These T cells are also expected to activate other T cells from the patient to act against the cancer cells.

The type of virus used in this medicine ('retrovirus') is modified in order not to cause disease in humans.

What is the stage of development of this medicine?

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 mantle cell lymphoma were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for mantle cell lymphoma 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 3 September 2015 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

EU/3/15/1552: Public summary of opinion on orphan designation: Autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3-zeta chimeric antigen receptor for the treatment of mantle cell lymphoma

Adopted Reference Number: EMA/COMP/596693/2015

Key facts

• Active substance:
  autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3-zeta chimeric antigen receptor (axicabtagene ciloleucel)
• Intended use:
  Treatment of mantle cell lymphoma
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/15/1552
• Date of designation:
  09/10/2015
• Sponsor:

  Kite Pharma EU B.V.; Tufsteen 1; 2132 NT Hoofddorp; Noord-Holland; The Netherlands; Tel. [phone]; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.