EU/3/07/523: Orphan designation for the treatment of gastro-entero-pancreatic neuroendocrine tumours

Gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) are a group of tumours that share a number of common characteristics, for example content of specific chemical substances called “neuroendocrine markers”. There are two main types of GEP-NET: carcinoid tumours, and “pancreatic-type” endocrine tumours (these often occur in the pancreas, but also in other sites). GEP-NET are chronically debilitating as they often produce and secrete hormonal substances that may cause severe symptoms, and are life-threatening if they spread to other organs in the body.

At the time of designation, GEP-NET affected approximately 1.6 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 80,000 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 based on data from the European Union (EU 27), Norway, Iceland and Lichtenstein. This represents a population of 498,000,000 (Eurostat 2006). This estimate is based on available information and calculations presented by the sponsor at the time of the application.

At the time of the application for orphan designation, several products were authorised in the Community for the treatment of one or more of GEP-NET. In most cases, these products are active against the symptoms caused by the secretion of hormones, but are not active against the growth of the tumours. Commonly, surgery and treatment with so called somatostatin analogues were used. Somatostatin analogues are similar to a naturally occurring hormone in the body called somatostatin that prevents the release of many hormones.

Lutetium(177Lu)-N-[(4,7,10-Tricarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic(2-7)disulfide may be of potential significant benefit, as it is expected to kill tumour cells, and thus reduce tumour size and eventually improve the long term outcome of the patients. These assumptions will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status.

Lutetium(177Lu)-N-[(4,7,10-Tricarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic(2-7)disulfide contains a somatostatin analogue together with a radioactive form of a chemical called Lutetium (177Lu). The product is expected to bind to the tumour cells thanks to the somatostatin analogue and to kill them with the radiation from the lutetium component.

The effects of lutetium (177Lu)-N-[(4,7,10-Tricarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic(2-7)disulfide were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical studies in patients with GEP-NET were ongoing.

Lutetium(177Lu)-N-[(4,7,10-Tricarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)acetyl]-D-phenylalanyl-L-cysteinyl-L-tyrosyl-D-tryptophanyl-L-lysyl-L-threoninyl-L-cysteinyl-L-threonine-cyclic(2-7)disulfide was not authorised anywhere worldwide for GEP-NET or designated as orphan medicinal product elsewhere for this condition, at the time of submission.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 December 2007 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.