EU/3/04/202 - orphan designation for treatment of MART-1 YES malignant melanoma in HLA-A2 YES patients

HLA-A2 restricted CD8 T-cell line expressing MART-1 T-cell receptor

Overview

On 21 June 2004, orphan designation (EU/3/04/202) was granted by the European Commission to CellCure ApS (currently CellCure A/S), Denmark, for HLA-A2 restricted CD8 T-cell line expressing MART-1 T-cell receptor for the treatment of MART-1 positive malignant melanoma in HLA-A2 positive patients.

What is MART-1 positive malignant melanoma in HLA-A2 positive patients?

Malignant melanoma is a cancer of the pigmented melanocytes, cells mostly found in the skin (e.g. in moles), but also present in many other organs, e.g. the eye and mucous membranes. Melanoma usually occurs in adults and adolescents. MART-1 (Melanoma Antigen Recognized by T cells) is a protein expressed on the surface of normal melanocytes and is almost always present in melanoma cells. MART-1 can be recognised by cells responsible for the immune response like T-cells.
HLA stands for human leukocyte antigen and cell surface receptors that are recognised by cells of the immune system. Recognition of HLA by the immune system gives the cell its identity as a member of the organism. On the contrary, any cell with an HLA recognised as foreign would trigger an immune response against it. HLA-A2 is one of the different types of leukocyte antigens that have been described in humans.
Malignant melanoma is life threatening, in particular due to poor survival in advanced stages of the disease.

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

At the time of designation MART-1 positive malignant melanoma affected 3.6 in 10,000 people in the European Union (EU) *. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 139,000 people.

*Disclaimer: The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 385,000,000 (Eurostat 2002) and may differ from the true number of patients affected by the condition.

What treatments are available?

Surgery is the first treatment applied to melanoma. There are also pharmacologic treatments that have been authorised in the Community for the treatment of melanoma. The choice of treatment depends on the extent of the melanoma lesion. Treatments include several medicinal products aimed at killing cancer cells (vincristine, dacarbazine, carmustine) or at stimulating an immune reaction against them (interferon-alpha). HLA-A2 restricted CD8 T-cell line expressing MART-1 T-cell receptor might be of potential significant benefit for the treatment of MART-1 positive malignant melanoma in HLA-A2 positive patients. This medicinal product could represent an additional treatment for use in combination with other treatments, and eventually improve the long-term outcome of the patients. The assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

How is this medicine expected to work?

This medicinal product is essentially a group of specialised cells of the immune system (body's defence mechanism against infection and disease) designed to bear on their surface the subtype A2 of the HLA-A and the receptor for the melanoma protein MART-1. On the cell surface, these cells also carry a molecule called CD8 which is involved in the activation of the immune system. This way, these cells are expected to attack only melanoma cells expressing MART-1 in HLA-A2 patients. After binding to MART-1, these immune cells are expected to destroy melanoma cells.

What is the stage of development of this medicine?

The effects of HLA-A2 restricted CD8 T-cell line expressing MART-1 T-cell receptor were evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials in HLA-A2 positive patients with were ongoing.
HLA-A2 restricted CD8 T-cell line expressing MART-1 T-cell receptor was not marketed anywhere worldwide for MART-1 positive malignant melanoma in HLA-A2 positive patients or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 14 May 2004 a positive opinion recommending the grant of the above-mentioned 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 Community) 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/3/04/202: Public summary of positive opinion for orphan designation of HLA-A2 restricted CD8 T-cell line expressing MART-1 T-cell receptor for the treatment of MART-1 positive malignant melanoma in HLA-A2 positive pa...

Adopted Reference Number: EMEA/COMP/297/04

Key facts

• Active substance:
  HLA-A2 restricted CD8 T-cell line expressing MART-1 T-cell receptor
• Intended use:
  Treatment of MART-1 YES malignant melanoma in HLA-A2 YES patients
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/04/202
• Date of designation:
  21/06/2004
• Sponsor:

  CellCure A/S; c/o Oestjysk Innovation; Gustav Wieds Vej 10; DK-8000 Arhus C; Denmark; Telephone: [phone]; E-mail: [e-mail]