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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/682567/2015

EMEA/H/C/002311

EPAR summary for the public

Votubia

everolimus

This is a summary of the European public assessment report (EPAR) for Votubia. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Votubia.

What is Votubia?

Votubia is a medicine that contains the active substance everolimus. It is available as tablets (2.5, 5 and 10 mg) and as dispersible tablets (2, 3 and 5 mg).

What is Votubia used for?

Votubia is used to treat the following benign (non-cancerous) tumours caused by the genetic disease tuberous sclerosis:

•    subependymal giant cell astrocytoma (SEGA), a benign tumour of the brain, where it is used in adults and children whose brain tumour cannot be surgically removed;

•    renal angiomyolipoma, a benign tumour of the kidneys, where it is used in adults who are at risk of complications but who do not require immediate surgery.

Because the number of patients with tuberous sclerosis is low, the disease is considered 'rare', and Votubia was designated an 'orphan medicine' (a medicine used in rare diseases) on 4 August 2010.

The medicine can only be obtained with a prescription.

How is Votubia used?

Votubia treatment should be started by a doctor experienced in treating tuberous sclerosis and in drug monitoring.

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Votubia is taken by mouth once a day at the same time every day, consistently either with or without food.

For SEGA, the starting dose depends on the body surface area (calculated using the patient's height and weight) and the patient's age, but the doctor will adjust the dose based on the patient's blood levels of the medicine and how well the patient tolerates the medicine.

In patients with renal angiomyolipoma, the recommended dose is 10 mg once a day. If patients experience severe side effects the doctor may need to reduce the dose or interrupt treatment temporarily.

Patients with mild or moderate impairment of liver function should be started at a lower dose. Votubia is not recommended for patients with SEGA and severe impairment of liver function. For patients with renal angiomyolipoma and severe impairment of liver function Votubia is only recommended if the desired benefit outweighs the risk.

How does Votubia work?

The active substance in Votubia, everolimus, is an anti-tumour medicine that acts by blocking an enzyme called 'mammalian target of rapamycin' (mTOR), which has increased activity in tumour cells of patients with SEGA or renal angiomyolipoma. In the body, everolimus first attaches to a protein called FKBP-12 that is found inside cells to make a 'complex'. This complex then blocks mTOR. Since mTOR is involved in the control of cell division and the growth of blood vessels, Votubia prevents the division of tumour cells and reduces their blood supply.

How has Votubia been studied?

In SEGA caused by tuberous sclerosis, Votubia has been studied in two main studies: the first study involved 28 adults and children aged three years and above. The main measure of effectiveness was based on how much the patient's main brain tumour shrank after six months of treatment. The second study involved 117 patients (including 20 children aged below 3 years) and compared Votubia with placebo (a dummy treatment). The main measure of effectiveness was the proportion of patients who responded to treatment and whose brain tumour shrank by at least half after six months of treatment.

In renal angiomyolipoma caused by tuberous sclerosis, Votubia has been compared with placebo in one study involving 118 adults. The main measure of effectiveness was the proportion of patients who responded to treatment and whose kidney tumour shrank by at least half.

What benefit has Votubia shown during the studies?

Votubia was shown to be effective at treating patients with SEGA and renal angiomyolipoma by shrinking the volume of the tumours.

In the first study in patients with SEGA, the main brain tumour shrank by half in approximately 30% of patients and by about a third in around 70% of patients. In the second study, the brain tumour shrank by at least half in 35% of patients (27 out of 78 patients) treated with Votubia, compared with none of the 39 patients who received placebo.

In patients with renal angiomyolipoma, the kidney tumour shrank by at least half in 42% of patients (33 out of 79 patients) treated with Votubia, compared with none of the 39 patients who received placebo.

What is the risk associated with Votubia?

The most common side effects with Votubia (seen in more than 1 in 10 patients) are acne, stomatitis (inflammation of the lining of the mouth), upper respiratory tract infections (colds), nasopharyngitis (inflammation of the nose and throat), sinusitis (inflammation of the sinuses), otitis media (infection of the middle ear), pneumonia (infection of the lung), increased blood levels of cholesterol, irregular menstruation (periods) and amenorrhoea (absence of periods). For the full list of all side effects reported with Votubia, see the package leaflet.

Votubia must not be used in people who are hypersensitive (allergic) to everolimus, to related medicines such as sirolimus and temsirolimus or to any of the other ingredients.

Why has Votubia been approved?

The CHMP noted that Votubia has been shown to reduce the size of the brain tumours in adults and children with tuberous sclerosis and that this is expected to reduce the signs and symptoms of SEGA such as seizures, hydrocephalus (accumulation of fluid in the brain), and increased pressure within the brain. Although surgery remains the standard treatment for this condition, Votubia is expected to benefit patients whose tumour cannot be operated on. Votubia has also been shown to reduce the size of kidney tumours in patients with renal angiomyolipoma. The side effects of the medicine were considered to be manageable and were generally mild or moderate. The CHMP therefore concluded that the benefits of Votubia outweigh its risks and recommended that it be given marketing authorisation.

Votubia was originally given 'conditional approval' because there was more evidence to come about the medicine, in particular its long-term effects. As the company has supplied the additional information necessary, the authorisation has been switched from conditional to full approval.

What measures are being taken to ensure the safe and effective use of Votubia?

A risk management plan has been developed to ensure that Votubia is used as safely as possible.

Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Votubia, including the appropriate precautions to be followed by healthcare professionals and patients.

Other information about Votubia

The European Commission granted a conditional marketing authorisation valid throughout the European Union for Votubia on 2 September 2011. This was switched to a full marketing authorisation on 16 November 2015.

The full EPAR for Votubia can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Votubia, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

The summary of the opinion of the Committee for Orphan Medicinal Products for Votubia can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/Rare disease designations.

This summary was last updated in 11-2015.

Votubia

EMA/682567/2015

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