EU/3/08/549: Orphan designation for the treatment of malignant mesothelioma

Malignant mesothelioma is a cancer of the membrane that surrounds the lungs (the pleura) or, less commonly, of the membrane that lines the abdomen (the peritoneum). 'Malignant' means that the cancer is likely to spread easily to other parts of the body. Mesothelioma is a very rare disease, but has become more frequent over the last few decades. It is seen more often in men than women. Although it can occur at any time of life, it usually appears at an age of around 60 years.

The major cause of mesothelioma is thought to be exposure to asbestos. Approximately eight out of ten people with mesothelioma have been exposed to asbestos in the past, typically 30 to 40 years before the cancer develops. Malignant mesothelioma is a life-threatening disease.

The most effective treatment for mesothelioma is the surgical removal of the tumour. However, this is not always possible because the tumour has often already spread to other parts of the body by the time it is diagnosed. The current standard treatment for malignant mesothelioma is pemetrexed, used in combination with cisplatin.

NGR-human tumour necrosis factor might be of potential significant benefit in the treatment of malignant mesothelioma because it has a novel mechanism of action. This assumption will need to be confirmed at the time of a marketing authorisation, to maintain the orphan status of the medicine.

Based on the information provided by the sponsor and previous knowledge of the Committee, malignant mesothelioma was considered to affect approximately 0.5 in 10,000 people in the European Union, which, at the time of designation, corresponded to about 25,000 persons.

* Disclaimer: For the purpose of the designation, the number of patients affected by the condition is estimated and assessed based on data from the European Union (EU 27), Norway, Iceland and Lichtenstein. This represents a population of 502,282,135 (Eurostat 2008). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

NGR-human tumour necrosis factor consists of two parts: NGR and human tumour necrosis factor:

• NGR is a protein that attaches to a receptor called CD13, which is found on the surface of the cells lining the new blood vessels that are formed around tumours;
• human tumour necrosis factor is a protein that can kill these cells.

Because it is attached to NGR, the cell-killing activity of tumour necrosis factor is concentrated at the cells lining the blood vessels formed around tumours. This combined effect results in damage to blood vessels supplying tumours, reducing its supply of oxygen and nutrients and leading to the tumour dying back.

At the time of submission of the application for orphan designation, no clinical trials were ongoing in patients with malignant mesothelioma.

At the time of submission, NGR-human tumour necrosis factor was not authorised anywhere in the world for malignant mesothelioma or designated as orphan medicinal product elsewhere for this condition.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 8 April 2008 a positive opinion recommending the granting of the above-mentioned designation.

• the seriousness of the condition,
• the existence or not of alternative methods of diagnosis, prevention or treatment and
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

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 the product's quality, safety and efficacy is necessary before it can be granted a marketing authorisation.