EU/3/12/963

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Orphan designation

On 22 May 2012, orphan designation (EU/3/12/963) was granted by the European Commission to TMC Pharma Services Ltd, United Kingdom, for chlormethine for the treatment of cutaneous T-cell lymphoma.

The sponsorship was transferred to Actelion Registration Limited, United Kingdom, in April 2014.

Chlormethine has been authorised in the EU as Ledaga since 3 March 2017. 

What is cutaneous T-cell lymphoma?

Cutaneous T-cell lymphoma (CTCL) is a cancer of the lymphatic system, a network of vessels that transport fluid from tissues through the lymph nodes and into the bloodstream. In CTCL there is uncontrolled growth of the T lymphocytes (T cells), a type of white blood cell found in the lymphatic system. The cancerous T cells appear in the skin, causing lesions (rashes, plaques and tumours) which can be itchy and painful.

CTCL usually happens in people aged between 40 and 60 years. In many cases, the disease is long lasting, with survival for more than 10 to 20 years being common. However, it can be a serious and life-threatening disease because it can develop into more aggressive forms of cancer. The condition may have a large impact on quality of life, particularly because the skin lesions can cause disfigurement.

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

At the time of designation, CTCL affected less than 2.6 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 132,000 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).


*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 27), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 509,000,000 (Eurostat 2012).

What treatments are available?

At the time of designation, several products were authorised for the treatment of CTCL within the EU. Treatments for CTCL can be divided into topical (applied to the skin) and systemic (affecting the whole body):

  • topical treatments include topical corticosteroids, the topical anticancer medicine carmustine, ultraviolet light and X-rays;
  • systemic treatments include cytotoxic medicines (medicines that kill cells that are dividing, such as cancer cells), interferon alfa (a medicine that helps the immune system to fight against the cancer cells) and photopheresis. Photopheresis is a technique in which blood is temporarily removed from the body to be treated with ultraviolet light. A substance is first added to the blood, that, when exposed to ultraviolet light, becomes activated and able to damage the T cells. When these damaged cells are re-introduced in the patient’s blood, they trigger the immune system to attack and kill cancerous T cells in the body.

The sponsor has provided sufficient information to show that chlormethine might be of significant benefit for patients with CTCL because it works in a different way to existing treatments and, when used in the early stages of the disease, it may improve the treatment options for patients with this condition when compared with other topical treatments. 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?

Chlormethine is a well-known anticancer medicine that belongs to the group ‘alkylating agents’. Alkylating agents kill cancer cells by attaching to their DNA while they are reproducing, that stops cell division. As a result, cancer cells cannot divide and this slows down the growth of tumours. For the treatment of CTCL, chlormethine is expected to be applied directly onto the skin in the form of a gel.

What is the stage of development of this medicine?

The effects of chlormethine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with chlormethine in patients with CTCL had finished.

At the time of submission, chlormethine was not authorised anywhere in the EU for CTCL. Orphan designation of chlormethine had been granted in the United States of America for CTCL.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 January 2012 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.

Name Language First published Last updated
EU/3/12/963: Public summary of opinion on orphan designation: Chlormethine for the treatment of cutaneous T-cell lymphoma (English only) 2012-07-06 2015-03-23

Key facts

Product details for <p>Chlormethine</p>
Active substanceChlormethine
Medicine Name
Disease/conditionTreatment of cutaneous T-cell lymphoma
Date of decision22/05/2012
OutcomePositive
Orphan decision numberEU/3/12/963

Review of designation

During its meeting of 17 to 19 January, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/12/963 for Ledaga (chlormethine) as an orphan medicinal product for the treatment of cutaneous T-cell lymphoma. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with cutaneous T-cell lymphoma. The COMP recommended that the orphan designation of the medicine be maintained*. 


The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Ledaga for:

‘the topical treatment of mycosis fungoides-type cutaneous T-cell lymphoma (MF-type CTCL) in adult patients’.

This falls within the scope of the product’s designated orphan indication, which is: ‘treatment of cutaneous T-cell lymphoma’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2012. Cutaneous T-cell lymphoma remains a debilitating and life-threatening condition because it can develop into a cancer that spreads more quickly and becomes infected, and it may have a large effect on the patient’s quality of life, particularly because the skin lesions can cause disfigurement.

Prevalence of the condition

The sponsor provided updated information on the prevalence of cutaneous T-cell lymphoma based on data from the scientific literature.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of cutaneous T-cell lymphoma remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was estimated to be approximately 2.7 people in 10,000. This is equivalent to a total of around 139,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, other treatments were authorised in the EU for the treatment of cutaneous T-cell lymphoma. They included treatment with ultraviolet light and x-rays as well as cytotoxic medicines (medicines that kill cells that are dividing, such as cancer cells) and interferon alfa (a medicine that helps the immune system to fight against the cancer cells), which were both given by injection.

 

Significant benefit of Ledaga

The COMP concluded that the claim of a significant benefit of Ledaga in cutaneous T-cell lymphoma is justified on the basis that this gel product offers the possibility for topical (applied to the skin) treatment for patients with this condition. Topical treatment with chlormethine is a therapeutic option for cutaneous T-cell lymphoma in current European guidelines. The COMP considered that the availability of a topical chlormethine product would therefore be a major contribution to patient care.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Ledaga is of significant benefit to patients affected by cutaneous T-cell lymphoma.

 

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Ledaga still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

 

Related information

Sponsor’s contact details

Actelion Registration Limited
Chiswick Tower 13th floor
389 Chiswick High Road
London W4 4AL
United Kingdom
Tel. + 44 (0)20 8987 3320
Fax + 44 (0)20 8987 3322
E-mail: registration@actelion.com

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases which includes a directory of patients’ organisations registered in Europe.
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.