EU/3/13/1200

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Orphan designation

On 13 November 2013, orphan designation (EU/3/13/1200) was granted by the European Commission to Bayer HealthCare AG, Germany, for sorafenib tosylate for the treatment of papillary thyroid cancer.

In May 2014, the sponsor changed name to Bayer Pharma AG.

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

What is papillary thyroid cancer?

Papillary thyroid cancer is a type of cancer affecting the thyroid, a small gland at the base of the neck that produces thyroid hormones. The thyroid is composed of two main cell types: follicular cells, which produce hormones that help regulate growth and metabolism (the process of breaking down substances in the body), and parafollicular cells, which produce a hormone called calcitonin that helps to regulate calcium levels in the blood. Papillary thyroid cancer originates in the follicular cells and it can spread to other parts of the body, usually via the lymphatic system.

Signs of papillary thyroid cancer are difficult to detect in the early stages of the disease and are usually limited to local swelling of the thyroid gland. Patients are often diagnosed when the disease has spread locally giving symptoms such as shortness of breath, difficulties in swallowing or changes in the voice.

Papillary thyroid cancer is a long-term debilitating disease which is life-threatening if it does not respond to treatment and if the cancer spreads to other parts of the body.

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

At the time of designation, papillary thyroid cancer affected between 1 and 3 in 10,000 people in the European Union (EU). This was equivalent to a total of between 51,000 and 154,000 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 on the basis of data from the European Union (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 512,200,000 (Eurostat 2013).

What treatments are available?

At the time of designation, the main treatment for papillary thyroid cancer in the EU was surgery to remove the thyroid. Therapy using radioactive iodine (131I) to destroy thyroid cells was also used.

Hormonal therapy was used as an additional treatment for preventing recurrence of the disease. In addition, the anticancer medicine doxorubicin was authorised for the treatment of papillary thyroid cancer in some EU Member States.
The sponsor has provided sufficient information to show that sorafenib tosylate might be of significant benefit for patients with papillary thyroid cancer because clinical studies indicate that it might improve the outcome of patients whose cancer does not respond to therapy with radioactive iodine. 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?

Sorafenib tosylate is a cancer medicine already authorised as Nexavar for the treatment of liver and kidney cancer. The medicine is a ‘protein kinase inhibitor’. This means that it blocks some specific enzymes known as protein kinases. These enzymes can be found in some receptors on the surface of cancer cells, where they are involved in the growth and spread of cancer cells, and in the blood vessels that supply the tumours, where they are involved in the development of new blood vessels. By blocking these enzymes, the medicine is expected to reduce the growth of cancer cells in patients with papillary thyroid cancer and cut off the blood supply that keeps cancer cells growing.

What is the stage of development of this medicine?

The effects of sorafenib tosylate have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with sorafenib tosylate in patients with papillary thyroid cancer were ongoing.

At the time of submission, sorafenib tosylate was authorised in the EU for the treatment of hepatocellular carcinoma (a type of liver cancer) and advanced renal-cell carcinoma (a type of kidney cancer).

At the time of submission, sorafenib tosylate was not authorised anywhere in the EU for papillary thyroid cancer. Orphan designation of sorafenib tosylate had been granted in the United States, Australia and Switzerland for some types of thyroid cancer, including papillary thyroid cancer.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 9 October 2013 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 align="left">Sorafenib tosylate</p>
Active substanceSorafenib tosylate
Medicine NameNexavar
Disease/conditionTreatment of papillary thyroid cancer
Date of decision13/11/2013
OutcomePositive
Orphan decision numberEU/3/13/1200

Review of designation

During its meeting of 13 to 14 May 2014, the Committee for Orphan Medicinal Products (COMP) reviewed the designations EU/3/13/1199 and EU/3/13/1200 for Nexavar (sorafenib) as an orphan medicinal product for the treatment of follicular and papillary thyroid cancers. The COMP assessed whether, at the time of addition of a new indication to the marketing authorisation, the medicinal product still met the criteria for orphan designation. The Committee looked at the seriousness and prevalence of the conditions, 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 follicular and papillary thyroid cancer. The COMP recommended that the orphan designations of the medicine be maintained1.


1 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 extending the approved therapeutic indication for Nexavar to include the following indication:
‘treatment of patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma, refractory to radioactive iodine’.

This falls within the scope of the product’s designated orphan conditions, which are: follicular and papillary thyroid cancers.

The COMP concluded that there had been no change in the seriousness of the conditions since the orphan designation in November 2013. Follicular and papillary thyroid cancers remain conditions that are debilitating in the long term and life threatening, particularly when the cancer does not respond to treatment and spreads to other parts of the body.

Prevalence of the condition

The sponsor provided information on the prevalence of follicular and papillary thyroid cancers based on data from the 2008 Globocan database.

On the basis of the information provided by the sponsor and the knowledge of the COMP, the COMP concluded that the prevalence of follicular and papillary thyroid cancers remains below the ceiling for orphan designation, which is 5 people in 10,000. At the time of the review of the orphan designations, the prevalence of follicular thyroid cancer was still estimated to be between 0.2 and 0.9 people in 10,000, and the prevalence for papillary thyroid cancer was still between 1 and 3 people in 10,000. This is equivalent to a total of between 10,000 and 46,000 people in the EU for follicular thyroid cancer, and between 51,000 and 153,000 people in the EU for papillary thyroid cancer.

Existence of other methods of treatment

At the time of the review of the orphan designation, the main treatment for follicular thyroid and papillary cancers in the EU was surgery to remove the thyroid. Therapy using radioactive iodine (131I) to destroy thyroid cells was also used. Hormonal therapy was used as an additional treatment for preventing recurrence of the disease. In addition, the anticancer medicine doxorubicin was authorised for the treatment of follicular and papillary thyroid cancers in one EU Member State.

Significant benefit of Nexavar

The COMP concluded that the claim of a significant benefit of Nexavar in follicular and papillary thyroid cancers is justified because of its demonstrated benefit in patients whose cancer has progressed or spread locally or to other parts of the body and does not respond to radioactive iodine. These patients have no appropriate treatment options.

The COMP conclusions are based on data from a main study involving patients with differentiated (papillary/follicular/Hürthle cell) thyroid cancer that had progressed or spread locally or to other parts of the body and did not respond to radioactive iodine. The study showed that Nexavar increased the time that patients lived without their disease getting worse by an average of about 5 months more than placebo (a dummy treatment).

Therefore, although other methods for the treatment of these conditions have been authorised in the EU, the COMP concluded that Nexavar is of significant benefit to patients affected by follicular and papillary thyroid cancer.

Conclusions

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

Sponsor’s contact details

Bayer Pharma AG
Müllerstrasse 178
13353 Berlin
Germany
Tel. +49 30 468 1111
Fax +49 30 468 15305
E-mail: bayer-pharma-gra-eu@bayer.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.