EU/3/16/1814: 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 heart or breathing problems, lung infections and bowel obstruction. Patients have very poor survival, only living for a year, on average, after diagnosis.

At the time of designation, malignant mesothelioma affected less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 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 513,700,000 (Eurostat 2016).

At the time of designation, the main treatments for malignant mesothelioma were surgery and chemotherapy (medicines to treat cancer) with or without radiotherapy (treatment with radiation). If the disease was too advanced for surgery, chemotherapy alone was used. One medicine, pemetrexed, was authorised throughout the EU for the treatment of malignant pleural mesothelioma. A second medicine, raltitrexed, was authorised for the treatment of malignant pleural mesothelioma in some European countries.

The sponsor has provided sufficient information to show that the medicine might be of significant benefit for patients with malignant mesothelioma because laboratory studies indicate it may reduce growth of tumours resistant to existing treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

Doxorubicin hydrochloride is a cancer medicine that has been used for many years. It is thought to work by interfering with the DNA within cells, preventing them from making more copies of DNA and making proteins. This means that cancer cells cannot divide and they eventually die.

In this medicine, doxorubicin hydrochloride is encapsulated within tiny fat-based particles (nanoparticles) which are attached to a peptide (a short chain of amino acids). This peptide targets a protein (nucleolin) found in high amounts in cancer cells, allowing the medicine to be delivered directly to the cancer.

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

At the time of submission of the application for orphan designation, no clinical trials with the medicine in patients with malignant mesothelioma had been started.

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 8 December 2016 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.