EU/3/05/344: Orphan designation for the treatment of medullary thyroid carcinoma

Thyroid cancer is a disease in which cancer (malignant) cells are found in certain tissues of the thyroid. The thyroid is a gland in the neck that is composed of mainly two different cell types: the follicular and parafollicular cells. The so-called follicular cells help to concentrate iodine and produce thyroid hormones. These hormones are important for the body growth and metabolism. The parafollicular cells produce a hormone called calcitonin that diminishes the calcium level in the blood. Depending on the type of cell in which the cancer cells originate, different types of thyroid cancer exist.

Medullary thyroid carcinoma is originating from the parafollicular cells (also called C cells), and represents only 5-9% of all thyroid cancers. Signs of cancer are difficult to detect in early stages of the disease and is often limited to a single local swelling of the thyroid gland which is not painful but can be felt by touching. Patients are frequently diagnosed when the disease has spread locally giving symptoms such as shortness of breath, difficulties in swallowing or changes in the voice. Some patients may have severe diarrhoea as a first sign of the disease.

Medullary thyroid carcinoma is a life-threatening disease.

At the time of designation, medullary thyroid carcinoma affected less than 0.7 in 10,000 people in the European Union (EU)*. This is equivalent to a total of fewer than 32,000 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 based on data from the European Union (EU 25), Norway, Iceland and Lichtenstein. This represents a population of 459,700,000 (Eurostat 2004).

No medicinal products were authorised for the treatment of medullary thyroid carcinoma in the Community at the time of submission of the application for orphan drug designation. The treatment consists of a complete surgical removal of the thyroid. When patients can no longer be managed by surgery alone, alternative effective treatment approaches are lacking.

Enzymes are proteins produced by the human body that speed up the transformation of certain substances into other substances. Vandetanib blocks (inhibits) a certain class of enzymes called tyrosine kinases. These enzymes play a role in a cascade of molecular reactions to bring a certain signal from outside the cell into the cell thereby controlling the growth of cells. In medullary thyroid carcinoma, the function of some of these enzymes is disturbed causing uncontrolled growth and multiplication of the cancer cells. By inhibiting this enzyme activity, Vandetanib might help in slowing down or stopping the further growth of the cancer cells.

The effects of vandetanib were evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials in patients with medullary thyroid carcinoma were ongoing.

Vandetanib was not authorised anywhere worldwide for medullary thyroid carcinoma, at the time of submission. Orphan designation of vandetanib was granted in the United States for the treatment of patients with follicular thyroid carcinoma, medullary thyroid carcinoma and anaplastic thyroid carcinoma and locally advanced or metastatic papillary thyrod carcinoma.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 7 December 2005 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.