EU/3/02/091

On 22 March 2002, orphan designation (EU/3/02/091) was granted by the European Commission to Antisense Pharma GmbH, Germany, for transforming growth factor (TGF)-β2-specific phosphorothioate antisense oligodeoxynucleotide for the treatment of high-grade glioma.

What is high-grade glioma?

Tumours that begin in the brain are known as primary brain tumours. Primary brain tumours are classified by the type of tissue from which they originate. The most common brain tumours are gliomas, which begin in the glial (supportive) tissue. There are several types of gliomas and these are grouped by grade, which refer to some cell characteristics that can be identified with a microscope. 

Cells from higher grade tumours are more abnormal looking and generally grow faster than cells from lower grade tumours. High-grade gliomas are more malignant than low grade tumours and are lifethreatening.

What are the methods of treatment available?

Treatment for high-grade gliomas depends on a number of factors and may include surgery, radiotherapy or chemotherapy as well as symptomatic treatments, such as corticosteroids to control the effects of raised intracranial pressure, and anticonvulsants to help control seizures, as required. Methods of treatment of the condition had been authorised at the time of submission of the application for orphan designation. Satisfactory argumentation has been submitted by the sponsor to justify the assumption that TGF- ß2 antisense oligonucleotide might be of potential significant benefit for the treatment of high-grade gliomas, particularly in terms of its novel mechanism of action.

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

According to the information provided by the sponsor, high-grade glioma was considered to affect about 26,000 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 377,000,000 (Eurostat 2001) 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?

The proposed TGF-ß2 antisense oligonucleotide is a synthetic 18-mer phosphorothioate oligodeoxynucleotide that was designed as complementary sequence to an appropriate area of the mRNA of the TGF-β2 gene. It is expected to inhibit the formation of TGF-β2, which is involved in the progression of high-grade gliomas. The product is administered directly into the brain tumour.

What is the stage of development of this medicinal product?

The effects of TGF-ß2 antisense oligonucleotide have been evaluated in experimental models. At the time of submission of the application, a clinical trial in patients with high-grade glioma was ongoing.

TGF-ß2 antisense oligonucleotide had not been marketed anywhere worldwide for high-grade glioma or designated as an orphan medicinal product elsewhere for this condition, at the time of submission.

According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 23 January 2002 a positive opinion recommending the grant of the above mentioned designation.

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

(i) the seriousness of the condition, (ii) the existence or not of alternative methods of diagnosis, prevention or treatment and (iii) either the rarity of the condition (considered to be affecting 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 have been 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.