EU/3/15/1588: Orphan designation for the treatment of gastro-entero-pancreatic neuroendocrine tumours

Gastro-entero-pancreatic neuroendocrine tumours (GEP-NETs) are tumours that arise from neuroendocrine cells in the gut. These cells release hormones that control various functions of the digestive system. The symptoms of GEP-NETs depend on where in the gut the tumour is growing and on whether it produces excess hormones. Often by the time of diagnosis the tumours have spread to other organs such as the liver.

GEP-NETs are debilitating as they often produce excess hormones that may cause severe symptoms. They are life-threatening if they spread to other organs in the body.

At the time of designation, GEP-NETs affected approximately 3.5 in 10,000 people in the European Union (EU). This was equivalent to a total of around 180,000 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 the application for orphan designation, several products were authorised in the EU for treating GEP-NETs, including octreotide and lanreotide for the management of symptoms, everolimus, and sunitinib.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with GEP-NETs because data from patients treated with the medicine showed reduction of tumour size and in the spread of the tumour to other parts of the body. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine stops gastrin from interacting with its receptor by blocking the receptor. Gastrin is a hormone that controls the release of acid into the stomach and organises and maintains the normal structure of the stomach lining. Excessive gastrin is thought to stimulate the growth of GEP-NETs. The medicine is expected to stop this growth by blocking the effect of gastrin.

The effects of (R)-1-[1-(4-acetoxy-3,3-dimethyl-2-oxo-butyl)-2-oxo-5-(pyridin-2-yl)-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl]-3-(3-methylamino-phenyl)-urea 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 GEP-NETs were ongoing.

At the time of submission, the medicine was not authorised anywhere in the EU for GEP-NETs 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 12 November 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.