EU/3/16/1811: 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 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 5-aminolevulinic acid might be of significant benefit for patients with glioma because early studies show that it may improve patients' survival when used in combination with authorised treatments. This assumption will need to be confirmed at the time of marketing authorisation, in order to maintain the orphan status.

When 5-aminolevulinic acid is absorbed by cells in the body, it is converted by enzymes into protoporphyrin IX (PPIX), a photosensitising agent (a substance that changes when exposed to light). Since glioma cells take up more of 5-aminolevulinic acid, higher levels of PPIX accumulate in the cancer cells than in normal tissue.

When red light of a specific wavelength is shone onto the brain tissue during surgery, the PPIX in the cancer cells is activated and reacts with oxygen in the cells to create a highly reactive and toxic type of oxygen called 'singlet oxygen' (a free radical). This is expected to kill the cancer cells by reacting with and destroying their internal components, such as their proteins and DNA.

The effects of 5-aminolevulinic acid have been evaluated in experimental models.

At the time of submission of the application for orphan designation, no clinical trials with 5-aminolevulinic acid for the treatment of patients with glioma had been started.

At the time of submission, 5-aminolevulinic acid was authorised in EU for the treatment of skin cancer and diagnosis of glioma. It was not authorised anywhere in the EU for treatment of 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 8 December 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.