EU/3/16/1621

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.

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 is based on the information provided by the sponsor and the 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 28), Norway, Iceland and Liechtenstein. This represents a population of 513,700,000 (Eurostat 2016).

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) to improve survival. 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 this medicine might be of significant benefit for patients with glioma because studies in experimental models showed that the medicine might reduce the size of the tumour and improve the survival of patients with glioma when given with radiotherapy or with temozolomide (a chemotherapy medicine often used in patients with glioma). This assumption will need to be confirmed at the time of marketing authorisation.

Delta-9-tetrahydrocannabinol and cannabidiol are substances found in the cannabis plant and are thought to act in different and complementary ways on glioma.

Delta-9-tetrahydrocannabinol is expected to work by blocking the action of proteins called 'mTORC1 complex'. This is expected to prevent the production of proteins needed for the glioma cells to grow. It also causes substances called sphingolipids to build up in glioma cells, causing them to die.

Cannabidiol is thought to reduce the production of other proteins needed by the cancer to grow and invade other cells (called MMP-2 and MMP-9) as well as to develop new blood vessels to supply the glioma with nutrients (called VEGF). It may also increase the effect of other medicines used for treating glioma.

The effects of delta-9-tetrahydrocannabinol and cannabidiol have been evaluated in experimental models.

At the time of submission of the application for orphan designation, clinical trials with delta-9-tetrahydrocannabinol and cannabidiol in patients with glioma were ongoing.

The combination of delta-9-tetrahydrocannabinol and cannabidiol was authorised as Sativex in a number of EU Member States for the treatment of multiple sclerosis.

At the time of submission, delta-9-tetrahydrocannabinol and cannabidiol 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.

• 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.