EU/3/15/1590

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Orphan designation

This medicine is now known as avelumab.

On 14 December 2015, orphan designation (EU/3/15/1590) was granted by the European Commission to Merck KGaA, Germany, for recombinant human monoclonal IgG1 antibody against programmed death ligand-1 for the treatment of Merkel cell carcinoma.

The sponsorship was transferred to Merck Serono Europe Limited, United Kingdom, in August 2016.

Recombinant human monoclonal IgG1 antibody against programmed death ligand-1 has been authorised in the EU as Bavencio since 18 September 2017.

What is Merkel cell carcinoma?

Merkel cell carcinoma (also known as cutaneous neuro-endocrine carcinoma) is a type of skin cancer that starts in ‘neuro-endocrine’ cells called Merkel cells. Neuro-endocrine cells release hormones into the blood when stimulated by the nervous system. Merkel cell carcinoma usually appears as a painless red-blue lump on the head and neck, but it can also be found on the arms and legs, and sometimes on the trunk.

Merkel cell carcinoma is a debilitating and life-threatening condition because it grows rapidly and spreads quickly to other parts of the body. Once this cancer has spread, it is associated with very poor long-term survival.

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

At the time of designation, Merkel cell carcinoma affected less than 0.4 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 21,000 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. This represents a population of 512,900,000 (Eurostat 2015).

What treatments are available?

At the time of designation, no satisfactory methods were authorised in the EU to treat Merkel cell carcinoma. Patients were treated with chemotherapy (medicines to treat cancer), surgery and radiotherapy (treatment with radiation). However, in most patients whose disease had spread, the disease usually came back after treatment.

How is this medicine expected to work?

This medicine is a ‘monoclonal antibody’, a type of protein designed to recognise and attach to a protein called ‘programme death ligand-1’ (PD-L1). This protein is expressed in many cancer cells and it is thought to help to suppress the body’s defences (immune cells) thereby protecting cancer cells from being attacked by the immune cells.

By attaching to the PD-L1 protein, the medicine is expected to remove this suppressive effect, allowing the immune cells to recognise and kill the cancer cells. In addition, by attaching to the cancer cells it is thought that the antibody helps to kill them directly. This is expected to slow down the growth of the cancer.

What is the stage of development of this medicine?

The effects of the medicine have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with Merkel cell carcinoma were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for Merkel cell carcinoma or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 November 2015 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>Recombinant human monoclonal IgG1 antibody against programmed death ligand-1 (avelumab)</p>
Active substanceRecombinant human monoclonal IgG1 antibody against programmed death ligand-1 (avelumab)
Medicine NameBavencio
Disease/conditionTreatment of Merkel cell carcinoma
Date of decision14/12/2015
OutcomePositive
Orphan decision numberEU/3/15/1590

Review of designation

On 25 July 2017, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/15/1590 for Bavencio (avelumab1) as an orphan medicinal product for the treatment of Merkel cell carcinoma. 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. The COMP recommended that the orphan designation of the medicine be maintained2.


1Previously known as recombinant human monoclonal IgG1 antibody against programmed death ligand-1.

2 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 Bavencio for: ‘treatment of adult patients with metastatic Merkel cell carcinoma’.

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

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2015. Merkel cell carcinoma remains a condition that is life threatening as it grows rapidly and spreads quickly to other parts of the body and once the cancer has spread, it is associated with very poor long-term survival.

Prevalence of the condition

The sponsor provided updated information on the prevalence of Merkel cell carcinoma 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 Merkel cell carcinoma 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 still estimated to be approximately 0.4 people in 10,000. This is equivalent to a total of fewer than 21,000 people in the EU.

Existence of other methods of treatment of Merkel cell carcinoma

The COMP noted that, at the time of the review of the orphan designation, no treatments were authorised in the EU for Merkel cell carcinoma.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that Bavencio 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

Merck Serono Europe Limited
56 Marsh Wall
London E14 9TP
United Kingdom
Tel. +44 (0)20 7987 1000
Fax +44 (0)20 7536 3388
E-mail: service@merckgroup.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.