EU/3/11/924

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Orphan designation

On 27 October 2011, orphan designation (EU/3/11/924) was granted by the European Commission to Celgene Europe Limited, United Kingdom, for lenalidomide for the treatment of mantle cell lymphoma.

Update: lenalidomide for treatment of mantle cell lymphoma has been authorised in the EU as Revlimid since 8 July 2016.

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 approximately 0.3 in 10,000 people in the European Union (EU)*. This is 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 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. This represents a population of 506,300,000 (Eurostat 2011).

What treatments are available?

The main treatments for mantle cell lymphoma available at the time of designation do not cure the disease and include 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). At the time of designation, temsirolimus was 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 lenalidomide might be of significant benefit for patients with mantle cell lymphoma because it works in a different way to existing treatments and might be used in combination with existing methods to improve the treatment of patients. 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?

Lenalidomide is an immunomodulating agent. This means that it affects the activity of the immune system (the body’s natural defences). Lenalidomide is expected to work in a number of different ways in mantle cell lymphoma: it blocks the production of cytokines (messenger molecules of the immune system) which help the tumour cells survive, prevents the growth of blood vessels within tumours and also stimulates some of the specialised cells of the immune system to attack the cancerous cells. It also increases production of a protein that blocks an enzyme involved in the control of cell division, to help slow down the growth and spread of the cancer.

What is the stage of development of this medicine?

The effects of lenalidomide have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with lenalidomide in patients with mantle cell lymphoma were ongoing.

At the time of submission, lenalidomide was authorised under the name ‘Revlimid’ for the treatment of multiple myeloma in the EU and in several countries outside the EU. Outside the EU, lenalidomide was also authorised for the treatment of myelodysplastic syndromes.

At the time of submission, orphan designation of lenalidomide had been granted in the United States for mantle cell lymphoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 September 2011 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.

Key facts

Product details for <p>Lenalidomide</p>
Active substanceLenalidomide
Medicine NameRevlimid
Disease/conditionTreatment of mantle cell lymphoma
Date of decision27/10/2011
OutcomePositive
Orphan decision numberEU/3/11/924

Review of designation

During its meeting of 14-16 June 2016, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/11/924 for Revlimid (lenalidomide) as an orphan medicinal product for the treatment of mantle cell lymphoma. The COMP assessed whether, at the time of addition of a new indication to the 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 mantle cell lymphoma. The COMP recommended that the orphan designation of the medicine be maintained.

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

The Committee for Medicinal Products for Human Use (CHMP) recommended extending the approved therapeutic indication for Revlimid to include the following indication:

‘Revlimid is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma’.

This falls within the scope of the product’s designated orphan indication, which is: ‘mantle cell lymphoma’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2011. Mantle cell lymphoma remains a condition that is debilitating in the long term, particularly due to enlarged lymph node, fever and weight loss, and is life-threatening with a median survival of 3 to 5 years.

Prevalence of the condition

The sponsor performed a search of the scientific literature and concluded that no publications are available which suggest a change in prevalence of mantle cell lymphoma.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of mantle 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 0.6 people in 10,000. This is equivalent to a total of around 31,000 people in the EU.

Existence of other methods of treatment

At the time of the review of the orphan designation, other treatments were used in the EU for the treatment of mantle cell lymphoma. The main treatments 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). At the time of review, the medicines ibrutinib and temsirolimus were specifically authorised in the EU for the treatment of relapsed or refractory mantle cell lymphoma (disease that has come back after previous treatment or has not responded to other treatments). The medicine pixantrone was authorised for non-Hodgkins lymphomas (a group of diseases that includes mantle cell lymphoma) that have failed several other treatments.

Significant benefit of Revlimid

The COMP concluded that the claim of a significant benefit of Revlimid in mantle cell lymphoma over temsirolimus and pixantrone is justified on the basis of comparisons of studies of Revlimid with studies using those medicines, which suggest that response to treatment and survival may be better with Revlimid. In addition, whereas those medicines are given into a vein, Revlimid is given by mouth which is easier and more convenient for patients.

The COMP initially had some concerns that a significant benefit in mantle cell lymphoma had not been demonstrated versus ibrutinib, which is also given by mouth. However, further analyses of the studies showed that Revlimid was effective in a group of patients with disease that had not responded to other treatments and to whom ibrutinib could not be given because they were also receiving treatment that increased their risk of bleeding.

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

Conclusions

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

Sponsor’s contact details:

Celgene Europe Limited
1 Longwalk Road
Stockley Park
Uxbridge UB11 1DB
United Kingdom
Telephone: +44 208 831 8300
Telefax: +44 208 831 8301
E-mail: medinfo.uk.ire@celgene.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.