EU/3/04/195

On 14 April 2004, orphan designation (EU/3/04/195) was granted by the European Commission to David Chaplin, United Kingdom, for 2-Methoxy-5-[(1Z)-2-(3,4,5-trimethoxyphenyl) ethenyl]-phenol (combretastatin A4 phosphate) for the treatment of anaplastic thyroid cancer.

What is 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 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. Anaplastic thyroid cancer is most likely originating from the follicular cells, and represents only 1-3% 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.

What are the methods of treatment available?

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.

What is the estimated number of patients affected by the condition?

According to the information provided by the sponsor, anaplastic thyroid cancer was considered to affect approximately 500 persons in the European Union.

*Disclaimer: The number of patients affected by the condition is estimated and assessed for the purpose of the designation, for a European Community population of 385,000,000 (Eurostat 2002) and may differ from the true number of patients affected by the condition. This estimate is based on available information and calculations presented by the sponsor at the time of the application.

How is this medicinal product expected to act?

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 the tumour growth and might even help to kill the tumour cells.

What is the stage of development of this medicinal product?

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 was granted in the United States for the treatment of anaplastic thyroid cancer, medullary thyroid cancer, stage IV papillary and stage IV follicular thyroid cancer.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 8 March 2004 a positive opinion recommending the grant of the above-mentioned designation.

Opinions on orphan medicinal products designations are based on the following cumulative criteria:

• the seriousness of the condition,
• the existence or not of alternative methods of diagnosis, prevention or treatment and 
• either the rarity of the condition (considered to affect not more than five in ten thousand persons in the Community) or the insufficient return of development investments.

Designated orphan medicinal products are still investigational products which were considered for designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy will be necessary before this product can be granted a marketing authorisation.