EU/3/00/004: Orphan designation for the treatment of glioblastoma

Tumours that begin in brain tissue are known as primary brain tumours. Primary brain tumours are classified by the type of tissue from which they originate, the most common being gliomas, which begin in the glial (supportive) tissue. Gliomas are classified according to the particular kind of cell they originate from and the severity of the tumour. Gliomas are graded according to their likely rate of growth, from grade 1 (slowest growing) to grade 4 (fastest growing). Grade 4 gliomas are usually the so called glioblastomas multiforme which are arising from astrocytic cells. Patients affected by glioblastoma can suffer from severe symptoms of the nervous system, depending on where in the brain the tumour develops. Glioblastoma is life-threatening.

At the time of designation glioblastoma affected approximately 0.12 to 0.18 in 10,000 people in the European Union (EU)*. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP). This is below the threshold for orphan designation which is 5 in 10,000. This is equivalent to a total of around 4,500 to 6,800 people.

*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 product was authorized for the treatment of glioblastoma in the Community at the time of submission of the application for orphan drug designation. Treatment for glioblastoma depends on a number of factors and encompasses several methods such as surgery, radiotherapy (using high-dose x-rays or other high-energy rays to kill cancer cells) or chemotherapy (using drugs to kill cancer cells), as well as some symptomatic treatments, including certain steroid hormones (corticosteroids) to control the effects of raised pressure within the skull, and medication to help control seizures.

Fluorouracil interrupts the action of thymidilate synthase, an enzyme (a protein that can trigger chemical reactions in the body) essential for processes involved in reproduction of genetic material (DNA) and cell proliferation (or cell division; cells increase in number by dividing). Tumour cells divide and increase in numbers more rapidly than healthy cells. By blocking thymidilate synthase, fluorouracil can eventually kill tumour cells. In this medicinal product, fluorouracil is contained in so-called microspheres, which will be implanted in the site of the cancer after surgical removal of the tumour. Once implanted there, the active substance is expected to destroy tumour cells remaining after surgery.

The effects of fluorouracil were evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials in patients with glioblastoma were ongoing.
Fluorouracil was authorised in many countries worldwide for the treatment of several cancers, at the time of submission. Orphan designation of fluorouracil was granted in the United States for the treatment of glioblastoma multiforme.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 13 September 2000 a positive opinion recommending the grant of the above-mentioned designation.

• the seriousness of the condition;
• the existence of alternative methods of diagnosis, prevention or treatment;
• and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the 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 the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.