EU/3/14/1398: Orphan designation for the treatment of malignant mesothelioma

Malignant mesothelioma is a cancer that affects the mesothelial cells (found on the inner linings of the organs), mainly in the pleura (lining the lungs) and in the peritoneum (lining the abdominal cavity). It is usually caused by exposure to asbestos. Mesothelioma of the pleura causes difficulty breathing and chest pain, and mesothelioma of the peritoneum causes ascites (a build-up of fluid in the abdomen) and abdominal pain.

Malignant mesothelioma is life-threatening because it may lead to bowel obstruction, heart or breathing problems and lung infections. Survival is poor, with patients only living, on average, for a year after diagnosis.

At the time of designation, malignant mesothelioma affected less than 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 26,000 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 28), Norway, Iceland and Liechtenstein. This represents a population of 511,100,000 (Eurostat 2014).

At the time of designation, the main treatment for malignant mesothelioma was surgery followed by chemotherapy (medicines to treat cancer) or radiotherapy (treatment with radiation). If the disease was too advanced for surgery, chemotherapy alone was used. Only one medicine, pemetrexed, was specifically authorised in the EU for the treatment of malignant pleural mesothelioma.

The sponsor has provided sufficient information to show that genetically modified serotype 5/3 adenovirus coding for granulocyte macrophage colony-stimulating factor might be of significant benefit for patients with the condition. Studies in experimental models have shown improved effects of the medicine when used together with currently available treatments, while early studies in patients showed benefits in patients whose disease had come back. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine contains a virus that has been modified so that it can only replicate (multiply) in cancer cells. When the medicine is injected into a patient with malignant mesothelioma cancer, the virus is expected to selectively attach to the cancer cells, multiply within the cells and then eventually kill them. In addition, the virus contains a gene so that it can produce a protein called 'granulocyte-macrophage colony-stimulating factor' (GM-CSF). GM-CSF is a protein that stimulates the immune system (the body's natural defences) to attack the cancerous cells.

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

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

At the time of submission, the medicine was not authorised anywhere in the EU for malignant mesothelioma 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 13 November 2014 recommending the granting of this designation.

• 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.