EU/3/15/1450

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Orphan designation

On 19 March 2015, orphan designation (EU/3/15/1450) was granted by the European Commission to Advanced Accelerator Applications SA, France, for gallium (68Ga)-edotreotide for the diagnosis of gastro-entero-pancreatic neuroendocrine tumours.

In September 2016, Advanced Accelerator Applications SA changed name to Advanced Accelerator Applications.

Gallium (68Ga)-edotreotide has been authorised in the EU as SomaKit TOC since 8 December 2016.

What are 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.

What is the estimated number of patients eligible for diagnosis?

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 elegible 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).

What methods of diagnosis are available?

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.

How is this medicine expected to work?

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.

What is the stage of development of this medicine?

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.

 

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.

Key facts

Product details for <p>Gallium (<sup>68</sup>Ga)-edotreotide</p>
Active substanceGallium (68Ga)-edotreotide
Medicine NameSomaKit TOC
Disease/conditionDiagnosis of gastro-entero-pancreatic neuroendocrine tumours
Date of decision19/03/2015
OutcomePositive
Orphan decision numberEU/3/15/1450

Review of designation

On 14 October 2016, the Committee for Orphan Medicinal Products (COMP) completed a review of the designation EU/3/15/1450 for SomaKit TOC (edotreotide, for use after radiolabelling as gallium (68Ga)-edotreotide) as an orphan medicinal product for the diagnosis of gastroenteropancreatic neuroendocrine tumours (GEP-NET). 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 diagnosis. As other methods of diagnosis are authorised in the European Union (EU), the COMP also considered whether the medicine is of significant benefit to patients with GEP-NET. 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.

Life-threatening or long-term debilitating nature of the condition

The Committee for Medicinal Products for Human Use (CHMP) recommended the authorisation of SomaKit TOC with the following indication:

‘After radiolabelling with gallium (68Ga) chloride solution, the solution of gallium (68Ga) edotreotide obtained is indicated for Positron Emission Tomography (PET) imaging of somatostatin receptor overexpression in adult patients with confirmed or suspected well-differentiated gastro-enteropancreatic neuroendocrine tumours (GEP-NET) for localizing primary tumours and their metastases’.

This falls within the scope of the product’s designated orphan indication, which is: ‘diagnosis of gastro-entero-pancreatic neuroendocrine tumours’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2015. GEP-NETs remain debilitating in the long term or life threatening, particularly due to the potentially severe symptoms, and the poor outcome in patients whose tumours have spread locally or to other parts of the body.

Prevalence of the condition

The sponsor provided updated information on the prevalence of GEP-NETs based on data from the scientific literature.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of GEP-NETs remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designation, the prevalence was still estimated to be approximately 3.5 people in 10,000. This is equivalent to a total of around 180,000 people in the EU.

Existence of other methods of diagnosis

At the time of the review of the orphan designation, other methods were authorised in the EU for the diagnosis of GEP-NETs. Those available included other medicines labelled with the radioactive elements indium-(111In), iodine-(123I) or technetium-(99mTc).

Significant benefit of SomaKit TOC

The COMP concluded that the claim of a significant benefit of SomaKit TOC in the diagnosis of GEP-NETs is justified on the basis of improved accuracy in detecting GEP-NETs compared with other available products, which thereby improves how GEP-NET could be managed.

Therefore, although other methods for the diagnosis of this condition have been authorised in the EU, the COMP concluded that SomaKit TOC is of significant benefit to patients affected by GEP-NETs.

Conclusions

Based on the data submitted and the scientific discussion within the COMP, the COMP considered that SomaKit TOC still meets the criteria for designation as an orphan medicinal product and that it should remain in the Community Register of Orphan Medicinal Products.

Further information on the current regulatory status of SomaKit TOC can be found in the European public assessment report (EPAR).

Related information

Sponsor’s contact details

Advanced Accelerator Applications
20 Rue Diesel
01630 Saint Genis Pouilly
France
Tel. +33 4 50 99 30 76
Fax +33 4 50 99 30 71
E-mail: regulatory_affairs@adacap.com

Patients' organisations

For contact details of patients’ organisations whose activities are targeted at rare diseases, see:

  • Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe;
  • European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.