EU/3/15/1571 - orphan designation for treatment of acute lymphoblastic leukaemia

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 11 November 2015, orphan designation (EU/3/15/1571) 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 acute lymphoblastic leukaemia.

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Please note that this product was withdrawn from the Union Register of orphan medicinal products in December 2021 on request of the Sponsor.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

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

At the time of designation, ALL affected approximately 1.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 87,000 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?

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 showed that patients whose disease had come back after previous treatment or did not respond to previous treatment responded to treatment with this medicine. 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 lymphocytes in patients with ALL 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 this medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, a clinical trial with the medicine including patients with ALL was ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for ALL 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 8 October 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/3/15/1571: 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 acute lymphoblastic l...

AdoptedReference Number: EMA/COMP/697370/2015

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 acute lymphoblastic leukaemia
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/15/1571
• Date of designation:
  11/11/2015
• 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.