EU/3/18/2098 - orphan designation for treatment of papillary thyroid cancer

Larotrectinib

Overview

Please note that this product (marketed as Vitrakvi) was withdrawn from the Community Register of designated orphan medicinal products in July 2019 upon request of the marketing authorisation holder at the time of the granting of a marketing authorisation.

On 19 November 2018, orphan designation (EU/3/18/2098) was granted by the European Commission to Bayer AG, Germany, for larotrectinib for the treatment of papillary thyroid cancer.

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 has 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 calcitonin, a hormone that helps to regulate calcium levels in the blood.

Papillary thyroid cancer starts in the follicular cells and it can spread to other parts of the body. 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 approximately 3.3 in 10,000 people in the European Union (EU). This was equivalent to a total of around 171,000 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).

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^*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 517,400,000 (Eurostat 2018).

 

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 medicines Nexavar (sorafenib), Lenvima (lenvatinib), Thyrogen (thyrotropin alfa) and doxorubicin were authorised for the treatment of papillary thyroid cancer.

The sponsor has provided sufficient information to show that larotrectinib might be of significant benefit for patients with papillary thyroid cancer. Early data indicate that patients in whom other treatments had failed responded to treatment with this medicine.

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?

Some patients with papillary thyroid cancer have genetic mutations (changes) called NTRK gene fusions which result in the production of altered TRK proteins that can cause cancer.

Larotrectinib blocks the activity of the altered TRK proteins, thus preventing or slowing down the growth of papillary thyroid cancer.

What is the stage of development of this medicine?

The effects of larotrectinib have been evaluated in experimental models.

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

At the time of submission, larotrectinib was not authorised anywhere in the EU for papillary thyroid cancer. Orphan designation of the medicine had been granted in the United States for soft tissue sarcoma, solid tumors with NTRK-fusion proteins and infantile fibrosarcoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 18 October 2018 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/3/18/2098: Public summary of opinion on orphan designation: Larotrectinib for the treatment of papillary thyroid cancer

Reference Number: EMA/776179/2018

Key facts

• Active substance:
  Larotrectinib
• Intended use:
  Treatment of papillary thyroid cancer
• Orphan designation status:
  Withdrawn
• EU designation number:
  EU/3/18/2098
• Date of designation:
  19/11/2018
• Sponsor:

  Bayer AG; 51368 Leverkusen; Germany; Tel. [phone]; E-mail: [e-mail]

Review of designation

The Committee for Orphan Medicinal Products reviewed the orphan designation of Vitrakvi at the time of marketing authorisation.

The sponsor formally requested the withdrawal of the orphan designation prior to the Committee’s final opinion. More information is available in the Vitrakvi : Orphan designation withdrawal assessment report (initial authorisation).