EU/3/13/1132: 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 (the lining of the lungs) and in the peritoneum (the lining of 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. Because the symptoms are not specific, the cancer is often detected at a late stage.

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

At the time of designation, malignant mesothelioma affected approximately 0.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 25,000 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 509,000,000 (Eurostat 2013).

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 the medicine might be of significant benefit for patients with malignant mesothelioma because early studies suggested it might reduce the number of cancer stem cells, which are thought to be a source of cancer cells and are also thought to encourage the spread of the disease and resistance to treatment. In addition, studies suggest that the medicine may be particularly beneficial to patients whose mesothelioma incorporates certain genetic mutations. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine blocks the action of certain enzymes, including the enzyme 'focal adhesion kinase' (FAK), which are involved in regulating cell function.

In mesothelioma, these enzymes are overactive and promote the growth and spread of the cancer cells and the development of new blood vessels that supply the tumours. By blocking these enzymes, the medicine is expected to reduce the growth and spread of the cancer.

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 malignant mesothelioma were planned.

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 17 April 2013 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.