EU/3/13/1119 - orphan designation for treatment of follicular thyroid cancer

Lenvatinib

Overview

Please note that this product (marketed as Lenvima) was withdrawn from the Community Register of designated orphan medicinal products in August 2018 upon request of the marketing authorisation holder.

On 26 April 2013, orphan designation (EU/3/13/1119) was granted by the European Commission to Eisai Europe Limited, United Kingdom, for lenvatinib for the treatment of follicular thyroid cancer.

Lenvatinib (Lenvima) has been authorised in the EU since 28 May 2015 for the treatment of adult patients with progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI).

The sponsorship was transferred to Eisai GmbH, Germany, in June 2018.

What is follicular thyroid cancer?

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. Follicular thyroid cancer originates in the follicular cells and it can spread to other parts of the body, usually via the blood stream.

Signs of follicular 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.

Follicular 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, follicular thyroid cancer affected less than 0.2 in 10,000 people in the European Union (EU). This was equivalent to a total of fewer than 10,000 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 designation, the main treatment for follicular 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 follicular 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 follicular 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 follicular thyroid cancer were ongoing.

At the time of submission, lenvatinib was not authorised anywhere in the EU for follicular thyroid cancer. Orphan designation of lenvatinib had been granted in the United States for the treatment of follicular, 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.

EU/3/13/1119: Public summary of opinion on orphan designation: Lenvatinib for the treatment of follicular thyroid cancer

AdoptedReference Number: EMA/COMP/193931/2013

Key facts

• Active substance:
  Lenvatinib
• Medicine name:
  Lenvima
• Intended use:
  Treatment of follicular thyroid cancer
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/13/1119
• Date of designation:
  26/04/2013
• Sponsor:

  Eisai GmbH; Lyoner Straße 36; 60528 Frankfurt am Main; Germany; Tel. [phone]; E-mail: [e-mail]

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.