EU/3/18/2098: Orphan designation for the treatment of 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.

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).

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.

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.

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.

• 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.