EU/3/13/1121

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Orphan designation

On 26 April 2013, orphan designation (EU/3/13/1121) was granted by the European Commission to Eisai Europe Limited, United Kingdom, for lenvatinib for the treatment of papillary thyroid cancer.

What is papillary thyroid cancer?

Papillary thyroid cancer is a type of cancer affecting the thyroid, a 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 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 less than 1 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 51,000 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 27), Norway, Iceland and Liechtenstein. This represents a population of 509,000,000 (Eurostat 2013).

What treatments are available?

At the time of orphan 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 re-occurrence 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 lenvatinib might be of significant benefit for patients with papillary thyroid cancer because early 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?

Lenvatinib is a ‘tyrosine-kinase inhibitor’. This means that it blocks the activity of enzymes known as tyrosine kinases. These enzymes can be found in certain receptors (such as VEGF, FGFR and RET receptors) on the surface of cancer cells, where they activate several processes including cell division and the growth of new blood vessels. By blocking the activity of VEGF receptors, the medicine reduces the blood supply to the cancer cells, slowing down the cancer’s growth. Lenvatinib also blocks the activity of FGFR and RET receptors, which appear to play a role in the growth of thyroid cancer cells.

The medicine is expected to be taken by mouth.

What is the stage of development of this medicine?

The effects of lenvatinib have been evaluated in experimental models.

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

At the time of submission, lenvatinib was not authorised anywhere in the EU for papillary thyroid cancer. Orphan designation of lenvatinib had been granted in the United States for the treatment of follicullar, medullary, anaplastic, and metastatic or locally advanced papillary thyroid cancer. Orphan designation had also been granted in Japan for the treatment of thyroid cancer.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 13 March 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">Lenvatinib</p>
Active substanceLenvatinib
Medicine Name
Disease/conditionTreatment of papillary thyroid cancer
Date of decision26/04/2013
OutcomePositive
Orphan decision numberEU/3/13/1121

Review of designation

During its meeting of 14 to 16 April 2015, the Committee for Orphan Medicinal Products (COMP) reviewed the designations EU/3/13/1119 and EU/3/13/1121 for Lenvima (lenvatinib)as an orphan medicinal product for the treatment of follicular and papillary thyroid cancers. 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 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 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 the authorisation of Lenvima for:

‘treatment of adult 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 indications, 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 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 updated information on the prevalence of follicular and papillary thyroid cancers based on data from the 2012 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 designation, the prevalence of follicular thyroid cancer was estimated to be approximately 0.6 people in 10,000, and the prevalence for papillary thyroid cancer was approximately 2.4 people in 10,000. This is equivalent to a total of around 31,000 people in the EU with follicular thyroid cancer, and around 123,000 people in the EU with papillary thyroid cancer.

Existence of other methods of treatment

At the time of the review of the orphan designation, the main treatment for follicular and papillary thyroid cancers in the EU was surgery to remove the thyroid, followed by therapy using radioactive iodine (131I) to destroy any remaining thyroid cells. In 2014, the medicine Nexavar (sorafenib) was authorised in the EU for the treatment of those patients whose differentiated (papillary/follicular/Hürthle cell) thyroid cancer had progressed or spread locally or to other parts of the body and did not respond to treatment with radioactive iodine.

Significant benefit of Lenvima

The COMP concluded that the claim of a significant benefit of Lenvima in follicular and papillary thyroid cancers is justified because Lenvima has been shown to improve progression-free survival (how long the patients lived without their disease getting worse) of patients whose cancer had progressed and had not responded to treatment with radioactive iodine. This is based on a main study in 392 patients, which showed that patients taking Lenvima lived an average of 18.3 months without their disease getting worse. This compares favorably with a progression-free survival of 10.8 months seen in patients treated with Nexavar in another study with a similar design to that with Lenvima.

Therefore, although other methods for the treatment of this condition have been authorised in the EU, the COMP concluded that Lenvima 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 Lenvima 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 Lenvima can be found in the European public assessment report (EPAR)

Sponsor’s contact details

Eisai Europe Ltd
European Knowledge Centre
Mosquito Way
Hatfield
Hertfordshire
AL10 9SN
United Kingdom
Tel. +44 (0)20 8600 1400
Fax +44 (0)8456 761504
E-mail: lmedinfo@eisai.net

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.