EU/3/15/1603 - orphan designation for treatment of pancreatic cancer
Live attenuated Listeria monocytogenes delta actA/delta inlB strain expressing human mesothelin
OrphanHuman
Overview
On 11 January 2016, orphan designation (EU/3/15/1603) was granted by the European Commission to Medpace Germany GmbH, Germany, for live attenuated Listeria monocytogenes delta actA/delta inlB strain expressing human mesothelin (also known as CRS-207) for the treatment of pancreatic cancer.
The sponsorship was transferred to Aduro Biotech Holdings, Europe B.V., The Netherlands, in April 2016.
Please note that this product was withdrawn from the Union Register of orphan medicinal products in December 2019 on request of the Sponsor.
Pancreatic cancer is cancer of the pancreas, a small organ that lies behind the stomach. The pancreas has two functions: to produce a fluid that helps with the digestion of food, and to produce hormones such as insulin. Due to the absence of symptoms in the early stages of pancreatic cancer, the majority of patients are diagnosed when the cancer has spread nearby or to other parts of the body.
Pancreatic cancer is a very severe and life-threatening disease that is associated with shortened life expectancy.
At the time of designation, pancreatic cancer affected less than 2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 103,000 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 512,900,000 (Eurostat 2015).
At the time of designation, several medicines were authorised in the EU for treating pancreatic cancer. The choice of treatment depended on several factors, including how far the disease had advanced. Treatments included surgery, radiotherapy (treatment with radiation) and chemotherapy (medicines to treat cancer).
The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with pancreatic cancer because early results suggest that it may improve survival of patients whose disease had not responded to previous therapy, when given as part of a combination treatment. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The 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 mesothelin. Mesothelin is found at high levels on many types of cancer cells, including pancreatic cancer cells.
When the medicine is injected into the body, the patient's immune system learns to treat mesothelin as 'foreign' and is expected to destroy pancreatic cancer cells carrying mesothelin on their surface.
The medicine is given as part of a combination treatment including another medicine (called 'two allogeneic irradiated pancreatic tumour cell lines' or GVAX) which is also expected to stimulate the immune system to recognise pancreatic cancer cells as foreign and so causes the body to attack the cancer.
The effects of this 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 pancreatic cancer were ongoing.
At the time of submission, the medicine was not authorised anywhere in the EU for pancreatic cancer. Orphan designation of the medicine had been granted in the United States for this condition.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 10 December 2015 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.
Key facts
- Active substance
- Live attenuated Listeria monocytogenes delta actA/delta inlB strain expressing human mesothelin
- Intended use
- Treatment of pancreatic cancer
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/15/1603
- Date of designation
- Sponsor
Aduro Biotech Holdings, Europe B.V.
Pivot Park RX 1101
Molenweg 79
5349 AC Oss
The Netherlands
Tel. +31 8 80 12 14 00
Fax +31 2 07 11 81 40
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: