EU/3/15/1553 - orphan designation for treatment of primary mediastinal large B-cell lymphoma

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

Overview

On 9 October 2015, orphan designation (EU/3/15/1553) 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 primary mediastinal large B-cell lymphoma.

The sponsorship was transferred to Kite Pharma EU B.V., Netherlands, in April 2017.

This medicine is now known as axicabtagene ciloleucel.

Autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3 zeta chimeric antigen receptor for treatment of primary mediastinal large B-cell lymphoma has been authorised in the EU as Yescarta since 23 August 2018.

The sponsor’s address was updated in September 2021.

What is primary mediastinal large B-cell lymphoma?

Primary mediastinal large B-cell lymphoma is an aggressive cancer of a type of white blood cell called B lymphocytes, or B cells. In patients with this cancer, the B cells multiply too quickly and live for too long. Patients with primary mediastinal large B-cell lymphoma usually present with a tumour mass in the chest cavity. The mass may cause breathlessness, coughing and swelling in the face and arm.

Primary mediastinal lymphoma is more common in women and typically affects people younger than 40 years. Although some people with primary mediastinal 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 initial treatment.

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

At the time of designation, primary mediastinal large B-cell lymphoma affected approximately 0.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 15,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 treatment for primary mediastinal large B-cell lymphoma was chemotherapy (medicines to treat cancer) usually in combination with other medicines called monoclonal antibodies and sometimes in combination with radiotherapy (treatment with radiation). Autologous haematopoietic (blood) stem-cell transplantation was also used in patients at risk of the disease coming back after treatment. This is a complex procedure where patients receive their own 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 primary mediastinal large B-cell lymphoma because preliminary studies showed that it may improve the outcome of patients whose disease has come back after previous treatment or did not respond to 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 primary mediastinal large B-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. The 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 primary mediastinal large B-cell lymphoma were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for primary mediastinal large B-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/3/15/1553: 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 primary mediastinal l...

AdoptedReference Number: EMA/COMP/597518/2015

Key facts

• Active substance:
  Autologous T cells transduced with retroviral vector encoding an anti-CD19 CD28/CD3-zeta chimeric antigen receptor (axicabtagene ciloleucel)
• Medicine name:
  Yescarta
• Intended use:
  Treatment of primary mediastinal large B-cell lymphoma
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/15/1553
• 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 reviewed the orphan designation of Yescarta at the time of marketing authorisation, and confirmed that the orphan designation should be maintained.

More information is available in the Yescarta : Orphan maintenance assessment report (initial authorisation).