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Orphan designation

On 17 July 2013, orphan designation (EU/3/13/1153) was granted by the European Commission to Janssen-Cilag International N.V., Belgium, for daratumumab for the treatment of plasma-cell myeloma.

Update: daratumumab has been authorised in the EU as Darzalex since 20 May 2016.

More information on Darzalex can be found in the European public assessment report (EPAR) on the Agency’s website.

What is plasma-cell myeloma?

Plasma-cell myeloma is a cancer of a type of white blood cells called plasma cells. Plasma cells originate from the bone marrow, the spongy tissue inside the large bones in the body. In plasma-cell 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.

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

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

At the time of designation, plasma cell myeloma affected approximately 1.75 in 10,000 people in the European Union (EU). This was equivalent to a total of around 90,000 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).

*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. At the time of designation, this represented a population of 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, several medicines were already authorised for plasma cell myeloma in the EU. The main treatment for plasma-cell 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 was sometimes used in combination with chemotherapy.

The sponsor has provided sufficient information to show that daratumumab might be of significant benefit for patients with plasma-cell myeloma because early studies have shown that it may improve the outcome of patients whose disease does not respond to or has come back after other 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?

Daratumumab is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a specific structure (an antigen) on the myeloma cells called ‘CD38’. Once attached, it is expected to activate the immune system to attack and kill the myeloma cells.

What is the stage of development of this medicine?

The effects of daratumumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with daratumumab in patients with plasma-cell myeloma were ongoing.

At the time of submission, daratumumab was not authorised anywhere in the EU for plasma-cell myeloma. Orphan designation of daratumumab had been granted in the United States for treatment of the condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 June 2013 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/3/13/1153: Public summary of opinion on orphan designation: Daratumumab for the treatment of plasma-cell myeloma (English only) 2013-08-16 2015-03-25

Key facts

Product details for <p>Daratumumab</p>
Active substanceDaratumumab
Medicine Name
Disease/conditionTreatment of plasma-cell myeloma
Date of decision17/07/2013
Orphan decision numberEU/3/13/1153

Review of designation

During its meeting of 19 to 21 April 2016, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/13/1153 for Darzalex (daratumumab)as an orphan medicinal product for the treatment of plasma cell myeloma (also known as 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 plasma cell myeloma. The COMP recommended that the orphan designation of the medicine be maintained1.

1The 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 a comparable 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 Darzalex be given conditional marketing authorisation for:

‘treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy’.

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

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2013. Plasma cell myeloma remains a debilitating and life-threatening condition because it disrupts the normal functioning of the bone marrow, leads to bone lesions and causes kidney failure.

Prevalence of the condition

The sponsor provided updated information on the prevalence of plasma cell myeloma based on data from the GLOBOCAN and NORDCAN 2012 databases, as well as data from the haematological malignancy research network.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of plasma cell 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 treatment

At the time of the review of the orphan designation, several medicines were authorised in the EU for treating plasma cell myeloma as first- and second-line therapies (in patients who had receive no or one previous treatment). The immunomodulatory agent pomalidomide and the medicine Farydak (panobinostat) were the only medicines authorised as third-line therapy, with similar indications to Darzalex.

Significant benefit of Darzalex

The COMP concluded that the claim of a significant benefit of Darzalex in plasma cell myeloma is justified based on study data in patients whose disease came back after, or did not respond to, at least two previous treatments including a proteasome inhibitor and an immunomodulatory agent. Results showed that around 31% of patients responded to treatment with Darzalex and the estimated overall survival was 20 months. In addition, indirect comparisons with Farydak, also authorised as third-line therapy, showed that Darzalex is more effective and has a better safety profile than Farydak.

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


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

Sponsor’s contact details

Janssen-Cilag International N.V.
Turnhoutseweg, 30
2340 Beerse
Tel. +32 1460 3189
Fax +32 1460 5533

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.