EU/3/19/2198 - orphan designation for treatment of glioma
adenoviral vector serotype 5 encoding the human interleukin-12 p70 transgene under the control of activator ligand veledimex
OrphanHuman
Overview
On 21 August 2019, orphan designation EU/3/19/2198 was granted by the European Commission to Ziopharm Oncology Limited, Ireland, for adenoviral vector serotype 5 encoding the human interleukin-12 p70 transgene under the control of activator ligand veledimex (also known as Ad-RTS-hIL-12) for the treatment of glioma.
Please note that this product was withdrawn from the Union Register of orphan medicinal products in March 2022 on request of the Sponsor.
Glioma is a brain tumour that affects glial cells (cells that surround and support nerve cells). It mainly affects adults aged over 45 years but it can occur at any age. Patients with glioma can have severe symptoms. The nature of their symptoms depends on where the tumour develops in the brain.
Symptoms can include headaches, nausea (feeling sick), loss of appetite, vomiting, muscle weakness in one part of the body and changes in personality, mood, mental capacity and concentration. About one-fifth of patients with glioma have seizures (fits) for months or years before the disease is diagnosed.
Glioma is a long-term debilitating and life-threatening disease because of the severe damage to the brain, and it is associated with poor long-term survival.
At the time of designation, glioma affected approximately 2.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 135,000 people1, 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).
1Disclaimer: 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 28), Norway, Iceland and Liechtenstein. This represents a population of 518,400,000 (Eurostat 2019).
At the time of designation, several medicines were authorised for the treatment of glioma in the EU. Treatments for glioma included surgery, radiotherapy (treatment with radiation), and chemotherapy (medicines to treat cancer). Patients also received treatments for the symptoms of glioma, including corticosteroids to reduce pressure within the skull and medicines to prevent seizures.
The sponsor has provided sufficient information to show that the medicine (in combination with another medicine called veledimex) might be of significant benefit for patients with glioma because early studies showed that patients lived longer compared with those who had received the usual treatment for glioma in previous studies. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.
The medicine is made of a virus modified to include a human gene that produces interleukin-12 (IL-12), a protein that activates the immune system (the body’s defences). The medicine is injected into the tumour where the gene is 'switched on’ by another medicine called veledimex, which the patient takes by mouth. By producing IL-12 in the tumour, the medicine is expected to help the immune system to fight the cancer, thereby leading to improvement of symptoms.
The virus used in this medicine (adenovirus) does not cause disease in humans.
The effects of the medicine have been evaluated in experimental models.
At the time of submission of the application for orphan designation, clinical trials with the medicine in patients with glioma were ongoing.
At the time of submission, the medicines was not authorised anywhere in the EU for the treatment of glioma. Orphan designation of the medicine had been granted in the United States for malignant glioma.
In accordance with Regulation (EC) No 141/2000, the COMP adopted a positive opinion on 18 July 2019, recommending the granting of this designation.
- 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.
Key facts
- Active substance
- adenoviral vector serotype 5 encoding the human interleukin-12 p70 transgene under the control of activator ligand veledimex
- Intended use
- Treatment of glioma
- Orphan designation status
- Withdrawn
- EU designation number
- EU/3/19/2198
- Date of designation
- Sponsor
Ziopharm Oncology Limited
Review of designation
The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.
EMA list of opinions on orphan medicinal product designation
EMA publishes information on orphan medicinal product designation adopted by the Committee for Orphan Medicinal Products (COMP) on the IRIS online platform:
Patients' organisations
For contact details of patients’ organisations whose activities are targeted at rare diseases, see:
Orphanet, a database containing information on rare diseases, which includes a directory of patients’ organisations registered in Europe.
European Organisation for Rare Diseases (EURORDIS), a non-governmental alliance of patient organisations and individuals active in the field of rare diseases.
EU register of orphan medicines
The list of medicines that have received an orphan designation in the EU is available on the European Commission's website: