EU/3/16/1618

On 16 February 2016, orphan designation (EU/3/16/1618) was granted by the European Commission to FLAG Therapeutics Ltd, UK, for N-(4-methoxyphenyl)-N,2,6-trimethylfuro[2,3-d]pyrimidin-4-amine for the treatment of glioma.

What is 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 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 is associated with poor long-term survival.

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

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 134,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000. This isbased 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 (EU 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

What treatments are available?

At the time of designation, several medicines were authorised for the treatment of glioma in the EU. Treatments included surgery, radiotherapy (treatment with radiation), and chemotherapy (medicines to treat cancer) to improve survival. Patients also received treatments for the symptoms of glioma, including corticosteroids to reduce pressure in the skull and medicines to prevent seizures.

The sponsor has provided sufficient information to show that this medicine might be of significant benefit for patients with glioma because studies in experimental models showed that the medicine might lead to greater reductions in the size of the tumour compared with temozolomide (a chemotherapy medicine often used in patients with glioma). This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

How is this medicine expected to work?

The medicine is thought to act in two different ways. Firstly, it attaches to a protein in cells called ‘tubulin’, which is important in the formation of the internal ‘skeleton’ that cells need to assemble when they divide. By attaching to tubulin in cancer cells, the medicine stops the formation of this skeleton, preventing the division and growth of the cancer cells.

Secondly, the medicine blocks the activity of several enzymes known as tyrosine kinases, such as those that are present in receptors called EGFR, PDGFR and VEGFR. These receptors are involved in the development of blood vessels and are found in high amounts in glioma cells. By blocking the tyrosine kinases in these receptors, the medicine is expected to prevent or slow the development of blood vessels that the cancer tissue needs to continue growing and spreading within the body.

What is the stage of development of this medicine?

At the time of submission of the application for orphan designation, the evaluation of the effects of the medicine in experimental models was ongoing.

At the time of submission, no clinical trials with the medicine in patients with glioma had been started.

At the time of submission, the 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 21 January 2016 recommending the granting of this designation.

Opinions on orphan medicinal product designations are based on the following three 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.

The Committee for Orphan Medicinal Products reviews the orphan designation of a product if it is approved for marketing authorisation.