EU/3/16/1754

On 14 October 2016, orphan designation (EU/3/16/1754) was granted by the European Commission to Ipsen Pharma, France, for lutetium-177(3+), S²,S⁷-cyclo[N-{4,7,10-tricarboxymethyl-1,4,7,10-tetraaza-cyclododecan-1-yl-acetyl}-4-chloro-L-phenylalanyl-D-cysteinyl-4-[(4S)-2,6-dioxo-1,3-diazinane-4-carboxamido]-L-phenylalanyl-4-(carbamoylamino)-D-phenylalanyl-L-lysyl-L-threonyl-L-cysteinyl-D-tyrosinamide] (also known as ¹⁷⁷Lu-OPS201) for the treatment of gastro-entero-pancreatic neuroendocrine tumours.

What are gastro-entero-pancreatic neuroendocrine tumours?

Gastro-entero-pancreatic neuroendocrine tumours (GEP-NETs) are tumours that usually arise from neuroendocrine cells in the gut or pancreas. These cells release hormones that control various functions of the digestive system. The symptoms of GEP-NETs depend on where 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 may cause severe symptoms and are life-threatening if they spread to other organs in the body.

What is the estimated number of patients affected by the condition?

At the time of designation, GEP-NETs affected approximately 3.8 in 10,000 people in the European Union (EU). This was equivalent to a total of around 195,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased on the information provided by the sponsor and the knowledge of the Committee for Orphan Medicinal Products (COMP).

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* 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 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of the application for orphan designation, several products were authorised in the EU for treating GEP-NETs, including everolimus, lanreotide, octreotide and sunitinib. Surgery was also used to remove or reduce the size of tumours.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with GEP-NETs because early data in patients with advanced, inoperable disease showed that their condition stabilised or improved. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

This medicine is made of a somatostatin analogue combined with a radioactive substance. A somatostatin analogue attaches to the same receptors as the natural hormone somatostatin. Somatostatin receptors are found in high amounts on GEP-NET cells. By attaching to these receptors, the medicine is expected to bring the radioactivity to the tumour cells and kill them.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

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, this 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 8 September 2016 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three criteria:

• 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.