EU/3/02/091 - orphan designation for treatment of high-grade glioma

TGF-ß2-specific phosphorothioate antisense oligodeoxynucleotide

Overview

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.

In February 2014, Antisense Pharma GmbH changed name to Isarna Therapeutics GmbH.

The sponsorship was transferred to Dr Ulrich Granzer, Germany in September 2016

The sponsorship was transferred to Granzer Regulatory Consulting & Services GmbH, Germany in March 2022.

For a list of the administrative updates to this public summary of opinion please refer to the PDF document below.

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

At the time of designation, high-grade glioma affected approximately 0.7 in 10,000 people in the European Union (EU). This was equivalent to a total of around 27,000 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).

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*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. At the time of designation, this represented a population of 380,600,000 (Eurostat 2002).

What treatments are 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.

How is this medicine expected to work?

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-?2 gene. It is expected to inhibit the formation of TGF-?2, 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 medicine?

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.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 23 January 2002 recommending the granting of this designation.

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

• 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.

EU/3/02/091: Public summary of positive opinion for orphan designation of TGF-β2-specific phosphorothioate antisense oligodeoxynucleotide for the treatment of high-grate glioma

Adopted Reference Number: EMEA/COMP/78/02 Rev. 2

Key facts

• Active substance:
  TGF-ß2-specific phosphorothioate antisense oligodeoxynucleotide
• Intended use:
  Treatment of high-grade glioma
• Orphan designation status:
  Positive
• EU designation number:
  EU/3/02/091
• Date of designation:
  22/03/2002
• Sponsor:

  Granzer Regulatory Consulting & Services GmbH;