EU/3/04/195: Orphan designation for the treatment of anaplastic thyroid cancer

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 mainly composed of two different cell types: follicular and parafollicular cells. The follicular cells help to concentrate iodine and produce thyroid hormones. These hormones are important for body growth and metabolism. The parafollicular cells produce a hormone called calcitonin, which 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. Anaplastic thyroid cancer is most likely to originate from the follicular cells, and represents only 1 to 3% of all thyroid cancers. Signs of cancer are difficult to detect in early stages of the disease, and 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. In 25 to 50% of the patients, the disease has spread to distant parts of the body, such as the lungs, at the moment of diagnosis. Anaplastic thyroid cancer is a life-threatening disease.

At the time of designation, anaplastic thyroid cancer affected approximately 0.01 in 10,000 people in the European Union (EU). This was equivalent to a total of around 500 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 25), Norway, Iceland and Liechtenstein. At the time of designation, this represented a population of 464,200,000 (Eurostat 2004).

There are no treatments available for anaplastic thyroid cancer. Surgery, if possible, is mainly done to control the local symptoms. Only in case of early diagnosis, extensive surgery followed by some local radiotherapy (using high-dose X-rays or other high-energy rays to kill cancer cells) or chemotherapy (using drugs to kill cancer cells) is considered the most appropriate treatment.

Combretastatin A4 phosphate is a substance that was originally isolated from the bark of the South African willow tree, Combretum caffrum. It is thought that combretastatin A4 phosphate acts on the cells of the vessels that bring blood to the tumour, blocking the normal flow of the blood. Cancer cells grow rapidly and thus require a large amount of blood. By blocking blood vessels combretastatin A4 phosphate might stop tumour growth and might even help to kill the tumour cells.

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

Combretastatin A4 phosphate was not marketed anywhere worldwide for anaplastic thyroid cancer at the time of submission.

Orphan designation of Combretastatin A4 phosphate had been granted in the United States for the treatment of anaplastic thyroid cancer, medullary thyroid cancer, and stage-IV papillary and stage-IV follicular thyroid cancer.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 8 March 2004 recommending the granting of this designation.

• the seriousness of the condition,
• the existence or not 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.