EU/3/11/920: Orphan designation for the diagnosis of gastro-entero-pancreatic neuroendocrine tumours

Gastro-entero-pancreatic neuroendocrine tumours (GEP-NETs) are tumours of the 'neuroendocrine system' in the gut. This is where the nervous and hormonal systems interact to control the digestive organs. GEP-NETs share a number of common characteristics, for example they share specific chemical substances called “neuroendocrine markers”. There are two main types of GEP-NETs: carcinoid tumours, and “pancreatic-type” endocrine tumours (these often occur in the pancreas, but may also be found in other sites). GEP-NETs are debilitating as they often secrete 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 eligible for diagnosis of gastro-entero-pancreatic neuroendocrine tumours was estimated to be less than 3.7 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 187,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 506,300,000 (Eurostat 2011).

At the time of designation, GEP-NETs were diagnosed using various methods. They included histopathology (examining a tissue specimen under the microscope) and biochemical testing (using chemical markers to measure substances produced by neuroendocrine tumours). Sometimes imaging methods such as magnetic resonance imaging (MRI) and computer tomography (CT) were used 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, the only agent authorised for use in scintigraphy was 111In-DTPA-pentetreotide (Octreoscan).

The sponsor has provided sufficient information to show that Gallium (⁶⁸Ga)-pasireotide tetraxetan might be of significant benefit for patients with GEP-NETs because early studies indicate that when used as an agent for scintigraphy it may improve the accuracy of diagnosis compared with existing methods. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

The product is an agent to be used for an imaging method called Positron Emission Tomography (PET). The product consists of a radioactive element, gallium (⁶⁸Ga), attached to pasireotide tetraxetan, a man-made substance which is similar to a natural hormone called somatostatin. Many somatostatin receptors are found on the surface of GEP-NETs cells. Once injected into a vein, gallium (68Ga)-pasireotide tetraxetan is expected to attach to these receptors on the GEP-NETs cells, and to omit radiation that can be detected by the PET imaging method, thereby allowing the tumour to be diagnosed.

The effects of gallium (⁶⁸Ga)-pasireotide tetraxetan were evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with gallium (⁶⁸Ga)-pasireotide tetraxetan in patients with GEP NETs had been started.

At the time of submission, gallium (⁶⁸Ga)-pasireotide tetraxetan 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 8 September 2011 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.