EU/3/12/1037

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Orphan designation

Please note that this product (marketed as Empliciti) was withdrawn from the Community Register of designated Orphan Medicinal Products by the European Commission in April 2016, at the time of the granting of a marketing authorisation.

On 9 August 2012, orphan designation (EU/3/12/1037) was granted by the European Commission to Bristol-Myers Squibb Pharma EEIG, United Kingdom, for elotuzumab for the treatment of multiple myeloma.

What is multiple myeloma?

Multiple myeloma is a cancer of a type of white blood cells called plasma cells. Plasma cells are found in the bone marrow, the spongy tissue inside the large bones in the body. In multiple myeloma, the division of plasma cells becomes out of control, resulting in abnormal, immature plasma cells multiplying and filling up the bone marrow. This interferes with production of normal white blood cells, red blood cells and platelets (components that help the blood to clot), leading to complications such as anaemia (low red blood cell counts), bone pain and fractures, raised blood calcium levels and kidney disease.

Multiple myeloma is a debilitating and life-threatening disease because it disrupts the normal functioning of the bone marrow, leads to bone destruction and causes kidney failure.

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

At the time of designation, multiple myeloma affected approximately 1.6 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 81,000 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?

At the time of submission of the application for orphan designation, several medicines were already authorised for multiple myeloma in the EU. The main treatment for multiple myeloma was chemotherapy (medicines to treat cancer) usually combined with steroids to reduce the activity of the immune system, the body’s natural defences. Where chemotherapy did not work, some patients received an allogeneic stem-cell transplant (a complex procedure where the patient receives stem cells from a matched donor to help restore the bone marrow). Radiotherapy (using radiation to kill cancer cells) was used to treat pain and weakened bones. Interferon alfa, a protein normally produced by the body during viral infections, was sometimes used in combination with chemotherapy.

The sponsor has provided sufficient information to show that elotuzumab might be of significant benefit for patients with multiple myeloma because it targets a specific protein found in high levels on the surface of the cancer cells, and preliminary studies indicated that when used in combination with other medicines it may improve the outcome of patients with this condition. 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?

Elotuzumab is a monoclonal antibody, a type of protein that has been designed to recognise and attach to a specific structure in the body. Elotuzumab is expected to attach to a protein called human CD-2 subset 1 (CS1) that is found at high levels on the surface of myeloma cells.

When elotuzumab attaches to CS1 on the surface of myeloma cells, it is expected to activate certain cells of the immune system, called natural killer cells. These cells will then attach to the antibody and kill the cancer cells. This is expected to slow down the growth or cause the shrinkage of multiple myeloma tumours.

What is the stage of development of this medicine?

The effects of elotuzumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with multiple myeloma were ongoing.

At the time of submission, elotuzumab was not authorised anywhere in the world for multiple myeloma. Orphan designation of elotuzumab had been granted in the United States of America for multiple myeloma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 July 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/3/12/1037: Public summary of opinion on orphan designation: Elotuzumab for the treatment of multiple myeloma (English only) 2012-09-26 2016-05-23

Key facts

Product details for <p>Elotuzumab</p>
Active substanceElotuzumab
Medicine Name
Disease/conditionTreatment of multiple myeloma
Date of decision09/08/2012
OutcomeWithdrawn
Orphan decision numberEU/3/12/1037

Review of designation

On 8 April 2016, the Committee for Orphan Medicinal Products (COMP) completed its review of the designation EU/3/12/1037 of Empliciti (elotuzumab) as an orphan medicinal product for the treatment of multiple myeloma. 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 multiple myeloma. The COMP concluded that one of the criteria for orphan designation was no longer met and therefore recommended that the orphan designation of the product should not be maintained1.


1The removal of the orphan designation at time of marketing authorisation means that the product cannot benefit from 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 can be placed on the market.

Life-threatening or chronically debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of Empliciti with the following indication:

‘Empliciti is indicated in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in adult patients who have received at least one prior therapy.’

This indication falls within the scope of the product’s designated orphan indication, which is ‘treatment of multiple myeloma’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2012. Multiple myeloma remains a condition that is debilitating in the long term and life threatening, particularly because it disrupts the normal functioning of the bone marrow, leads to bone destruction and causes kidney failure.

Prevalence of the condition

The sponsor provided updated information on the prevalence of multiple myeloma based on data from GLOBOCAN 2012, an international web portal for cancer research.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of multiple myeloma 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 less than 4 people in 10,000. This is equivalent to a total of fewer than 205,000 people in the EU.

Existence of other methods of treatments

At the time of the review of the orphan designation, bortezomib, carfilzomib, doxorubicin and lenalidomide were authorised in the EU for the treatment of patients with multiple myeloma who had received at least one previous treatment (‘second-line therapy’). Carfilzomib, an orphan medicine, was the most recent to have received marketing authorisation.

Significant benefit of Empliciti

The COMP concluded that the claim of a significant benefit of Empliciti in multiple myeloma is no longer justified. In indirect comparisons between Empliciti and carfilzomib, 2-year survival was similar with both treatments (at around 73%) and overall survival did not appear to be greater with Empliciti. In addition, analyses of outcomes in different subgroups of patients did not conclusively show a better efficacy or safety with Empliciti.

Therefore, the COMP concluded that Empliciti did not meet the criteria for significant benefit assumed at the time of the original orphan designation.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP concluded that Empliciti no longer meets one of the criteria for designation as an orphan medicinal product. Therefore, the COMP recommended that the product should be removed from the Community Register of Orphan Medicinal Products.

Sponsor’s contact details:

Bristol-Myers Squibb Pharma EEIG
Uxbridge Business Park
Sanderson Road
Uxbridge UB8 1DH
United Kingdom
Telephone: +44 18 95 52 37 40
Telefax: +44 18 95 52 36 77
E-mail: medical.information@bms.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.