EU/3/14/1409: 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.

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 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of around 10,000 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 pegylated recombinant arginine deiminase might be of significant benefit for patients with malignant mesothelioma because early clinical studies showed that it might improve the outcome of patients with this condition when used with standard treatment for malignant mesothelioma. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The medicine is made of an enzyme, arginine deiminase, which breaks down an aminoacid called arginine, a substance that is needed by cancer cells to grow. Cancer cells are unable to produce their own arginine and therefore they take it directly from the blood. When administered to patients with malignant mesothelioma, arginine deiminase breaks down the arginine present in the blood, and the cancer cells are thus deprived of their supply. As a consequence they cannot grow and eventually die.

The medicine is produced by a method known as 'recombinant DNA technology': the enzyme is made by bacteria into which a gene (DNA) has been introduced that makes them able to produce it. The enzyme has also been modified by a process called 'pegylation', meaning that it has been attached to a chemical called polyethylene glycol, which is expected to prolong the time needed to remove the medicine from the body.

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 ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for malignant mesothelioma. Orphan designation of the medicine had been granted in the United States for mesothelioma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 December 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.