EU/3/15/1594

On 14 December 2015, orphan designation (EU/3/15/1594) was granted by the European Commission to Medpace Germany GmbH, Germany, for live attenuated Listeria monocytogenes delta actA/delta inlB strain expressing human mesothelin for treatment of malignant mesothelioma.

The sponsorship was transferred to Aduro Biotech Holdings, Europe B.V., The Netherlands, in April 2016.

What is 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.

What is the estimated number of patients affected by the condition?

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 isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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* 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 512,900,000 (Eurostat 2015).

What treatments are available?

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 clinical studies showed that it might improve the outcome of patients with this condition when added to 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.

How is this medicine expected to work?

This medicine works by stimulating the patient’s immune system, the body’s natural defences, so that it targets and destroys the cancer cells. It is made of Listeria monocytogenes bacteria, which have been attenuated (weakened) so that they do not cause disease in humans. The bacteria have also been modified to produce large amounts of the mesothelin protein. Mesothelin is found at high levels on many types of cancer cells, including mesothelioma cells.

When the medicine is given, the patient’s immune system is expected to learn to treat mesothelin as ‘foreign’. This is expected to stimulate an immune response against the mesothelioma cells carrying mesothelin on their surface, resulting in the immune system attacking and destroying the cancer cells.

What is the stage of development of this medicine?

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 12 November 2015 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.