EU/3/12/1004

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Orphan designation

On 4 July 2012, orphan designation (EU/3/12/1004) was granted by the European Commission to Eli Lilly Nederland B.V., the Netherlands, for ramucirumab for the treatment of gastric cancer.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

What is gastric cancer?

Gastric cancer is a cancer that starts in the stomach, generally in the glandular cells lining the inside of the stomach. Gastric cancer is often detected late as the early signs of the disease are the same as those of less serious stomach conditions (heartburn, gas, excessive belching). At a later stage, gastric cancer causes unexplained weight loss, loss of appetite and general decline in health. Bleeding can occur, leading to anaemia (low red blood cell counts). Men are about twice as likely to develop the disease as women.

Gastric cancer is a serious and life-threatening illness that is associated with shortened life expectancy.

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

At the time of designation, gastric cancer affected not more than 3 in 10,000 people in the European Union (EU). This was equivalent to a total of not more than 153,000 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).


*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. At the time of designation, this represented a population of 509,000,000 (Eurostat 2012).

What treatments are available?

At the time of designation, some patients with gastric cancer were treated with surgery to remove part or the whole of the stomach. Chemotherapy (medicines to treat cancer) was generally used after surgery or on its own if surgery was not possible or the disease had spread to other parts of the body. Several chemotherapy medicines were authorised in the EU for use in gastric cancer, such as cisplatin, docetaxel, doxorubicin, capecitabine, epirubicin, 5-fluorouracil, mitomycin and trastuzumab. They were often used in combination.

The sponsor has provided sufficient information to show that ramucirumab might be of significant benefit for patients with gastric cancer because early studies suggest it may partly improve the symptoms of patients with gastric cancer who had not responded to other treatments. 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?

Ramucirumab is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a receptor called ‘vascular endothelial growth factor receptor’ (VEGFR), found on the surface of cancer cells. It thereby blocks the action of vascular endothelial growth factor (VEGF), which is present at high levels in gastric tumours and is responsible for the development of new blood vessels that supply the tumours. This slows down the growth of cancer cells by reducing their blood supply.

What is the stage of development of this medicine?

The effects of ramucirumab have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with ramucirumab in patients with gastric cancer were ongoing.

At the time of submission, ramucirumab was not authorised anywhere in the EU for gastric cancer. Orphan designation of ramucirumab had been granted in the United States of America for gastric cancer.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 11 May 2012 recommending the granting of this designation.

Update: ramucirumab (Cyramza) has been authorised in the EU since 19 December 2014. Cyramza monotherapy is indicated for the treatment of adult patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma with disease progression after prior platinum or fluoropyrimidine chemotherapy, for whom treatment in combination with paclitaxel is not appropriate.

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.

Name Language First published Last updated
EU/3/12/1004: Public summary of opinion on orphan designation: Ramucirumab for the treatment of gastric cancer (English only) 24/07/2012 12/03/2015

Key facts

Product details for <p>Ramucirumab</p>
Active substanceRamucirumab
Medicine NameCyramza
Disease/conditiontreatment of gastric cancer
Date of decision04/07/2012
OutcomePositive
Orphan decision numberEU/3/12/1004

Review of designation

During its meeting of 11-13 November 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designation EU/3/12/1004 for Cyramza (ramucirumab)as an orphan medicinal product for the treatment of gastric cancer. 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 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 gastric cancer. The COMP recommended that the orphan designation of the medicine be maintained*.


*The 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 a comparable 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 that Cyramza should be used as follows:

  • in combination with paclitaxel for the treatment of adult patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma with disease progression after prior platinum and fluoropyrimidine chemotherapy;
  • as monotherapy for the treatment of adult patients with advanced gastric cancer or gastro-oesophageal junction adenocarcinoma with disease progression after prior platinum or fluoropyrimidine chemotherapy, for whom treatment in combination with paclitaxel is not appropriate.

This falls within the scope of the product’s designated orphan indication, which is: ‘gastric cancer’.

The COMP concluded that there had been no change in the seriousness of the condition since the orphan designation in 2012. Gastric cancer remains a long-term debilitating and life-threatening condition with a short life expectancy.

Prevalence of the condition

The sponsor provided updated information on the prevalence of gastric cancer 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 gastric cancer 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 estimated to be not more than 4 people in 10,000. This is equivalent to a total of not more than 204,000 people in the EU.

Existence of other methods of treatment

The COMP noted that, at the time of the review of the orphan designation, the main treatments for gastric cancer were surgery and/or chemotherapy (medicines to treat cancer), such as platinum and fluoropyrimidine–based therapy.

Significant benefit of Cyramza

The COMP concluded that the claim of a significant benefit of Cyramza in gastric cancer is justified because Cyramza, in combination with paclitaxel, improves the survival of patients whose cancer has come back despite a previous treatment with platinum and/or a fluoropyrimidine. This is based in a study which showed that patients treated with Cyramza and paclitaxel lived longer on average than patients treated with paclitaxel and placebo (a dummy treatment): 9.6 months versus 7.4 months respectively.

In addition, for patients for whom Cyramza in combination with paclitaxel is not appropriate, the COMP concluded that the claim of significant benefit of Cyramza on its own is justified because these patients tolerate this treatment better than other cancer treatments.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Cyramza is of significant benefit for patients affected by gastric cancer.

Conclusions

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

Related information

Sponsor’s contact details

Eli Lilly Nederland B.V.
Grootslag 1-5
3991 Houten
The Netherlands
Tel. +31 3060 25800
Fax +31 3060 25888
E-mail: eu_orphan@lilly.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.