EU/3/09/709: Orphan designation for the treatment of glioma

Glioma is a type of brain tumour that affects the 'glial' cells (the cells that surround and support the nerve cells). Patients with glioma can have severe symptoms, but the types of symptoms experienced depend on where the tumour develops in the brain. Symptoms can include headaches, nausea (feeling sick), loss of appetite, vomiting, and changes in personality, mood, mental capacity and concentration. About a fifth of patients with glioma have seizures (fits) for months or years before the disease is diagnosed.

Glioma is a debilitating and life-threatening disease because of the severe damage to the brain that is associated with poor long-term survival.

At the time of designation, glioma affected approximately 1 in 10,000 people in the European Union (EU)*. This is equivalent to a total of around 50,000 people, and is below the threshold for orphan designation, which is 5 people in 10,000. This is based on the information provided by the sponsor and knowledge of the Committee for Orphan Medicinal Products (COMP).

*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 (EU 27), Norway, Iceland and Liechtenstein. This represents a population of 504,800,000 (Eurostat 2009).

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 recombinant fusion protein consisting of the extracellular portion of CD95 fused to the Fc part of a human IgG1 molecule might be of significant benefit for patients with glioma because it works in a different way to existing treatments and because early studies indicate that it might improve the overall outcome of patients with this condition. These assumptions will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

This medicine is a 'fusion' protein that is made up of two components:

• a portion of CD95, a receptor that is found in large amounts on the surface of glioma cels;
• a part of a human IgG1 molecule, a type of human antibody that can bind to specific structures and help the body to fight infections and other diseases.

These two components are artificially engineered to form an antibody-like compound that is expected to attach to CD95L. CD95L is a substance that is involved in the growth and spread of cancer cells. It normally attaches to CD95 and activates the receptor. By attaching to CD95L, this medicine blocks its activity, therefore blocking the migration of glioma cells further into the brain. This is expected to slow down the spread of glioma.

The effects of recombinant fusion protein consisting of the extracellular portion of CD95 fused to the Fc part of a human IgG1 molecule have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials of this medicine in patients with glioma had been started.

At the time of submission, this medicine was not authorised anywhere in the EU for glioma or designated as an orphan medicinal product elsewhere for this condition.

In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 5 November 2009 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 Community) 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.