EU/3/16/1781

On 18 November 2016, orphan designation (EU/3/16/1781) was granted by the European Commission to APCure SAS, France, for live-attenuated non-replicative Pseudomonas aeruginosa strain expressing large T antigen of Merkel cell polyomavirus for the treatment of Merkel cell carcinoma.

What is Merkel cell carcinoma?

Merkel cell carcinoma (also known as cutaneous neuro-endocrine carcinoma) is a 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 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 people¹, 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).

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¹Disclaimer: 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 513,700,000 (Eurostat 2016).

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 surgery and radiotherapy (treatment with radiation). Chemotherapy (medicines to treat cancer) was used for cancer that had spread.

How is this medicine expected to work?

The medicine works by stimulating the patient’s immune system, the body’s natural defences, so that it targets and destroys cancer cells. It is made of Pseudomonas aeruginosa bacteria, which have been attenuated (weakened) so that they do not cause disease and cannot multiply in the body. The bacteria have also been modified to produce the protein Large T (LT) which is found in a majority of Merkel cell carcinomas.

When the medicine is injected into the body, the patient’s immune system is activated by the Pseudomonas aeruginosa and learns to treat LT as ‘foreign’. This encourages the immune system to attack the cancer cells in Merkel cell carcinoma because they have the LT protein, so reducing the growth of the cancer.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

No clinical trials had been started in patients with Merkel cell carcinoma.

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 6 October 2016 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.