This medicine is now known as lutetium (177Lu) oxodotreotide.
On 31 January 2008, orphan designation (EU/3/07/523) was granted by the European Commission to BioSynthema Global Operations B.V, the Netherlands, for 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 for the treatment of gastro-entero-pancreatic neuroendocrine tumours.
The sponsorship was transferred to Advanced Accelerator Applications, France, in September 2011.
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 has been authorised in the EU as Lutathera since 26 September 2017.
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.
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.
Advanced Accelerator Applications
8 Rue Henri Sainte Claire Deville
92500 Rueil-Malmaison
France
E-mail: Regulatory_Affairs@adacap.com
On 25 July 2017, the Committee for Orphan Medicinal Products (COMP) completed a review of the designation EU/3/07/523 for Lutathera (lutetium (177Lu) oxodotreotide) as an orphan medicinal product for the treatment of gastro-entero-pancreatic neuroendocrine tumours. The COMP assessed whether, at the time of marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the condition, and the existence of other methods of treatment. As other methods of treatment are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with gastro-entero-pancreatic neuroendocrine tumours. The COMP recommended that the orphan designation of the medicine be maintained1.
1The maintenance of the orphan designation at time of marketing authorisation would, except in specific situations, give an orphan medicinal product 10 years of market exclusivity in the EU. This means that in the 10 years after its authorisation similar products with the same therapeutic indication cannot be placed on the market.
| Date | Update |
|---|---|
| May 2023 | The sponsor’s address was updated. |
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
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.
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: