EU/3/15/1450: Orphan designation for the diagnosis 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 the tumour is located within the gut 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 long-term 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, the number of patients expected to use the medicine for diagnosis of GEP-NETs was estimated to be 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 eligible for diagnosis of 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, GEP-NETs were diagnosed using various methods. These included histopathology (examining a tissue under the microscope) and biochemical testing (measuring substances produced by neuroendocrine tumours), as well as imaging methods such as magnetic resonance imaging (MRI) and computer tomography (CT) to visualise the location of the tumour. Somatostatin receptor scintigraphy was a commonly used imaging technique, employing a radioactive tracer to obtain an image. At the time of designation, ¹¹¹In-DTPA-pentetreotide (Octreoscan) was authorised in the EU for use in scintigraphy.

The sponsor has provided sufficient information to show that the medicinal product might be of significant benefit for patients with GEP-NETs because early studies in experimental models indicate that it may improve the accuracy of detecting tumours compared with somatostatin receptor scintigraphy. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is to be used for an imaging method called positron emission tomography (PET). It consists of a radioactive element, gallium (⁶⁸Ga), attached to a substance containing a somatostatin analogue, a substance similar to a natural hormone called somatostatin. Most GEP-NETs have high amounts of somatostatin receptors on their surface. The product is expected to attach to these somatostatin receptors and to accumulate in the GEP-NETs cells. These cells are then expected to emit radiation that can be detected by the PET imaging method. This allow to determine the location of the tumour and if it has spread to other parts of the body.

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

At the time of submission of the application for orphan designation, no clinical trials with the product in patients with GEP-NETs had been started.

At the time of submission, the product was not authorised anywhere in the EU for the diagnosis of GEP-NETs or designated as an orphan medicinal product elsewhere for diagnosing this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 12 February 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.