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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/752274/2015

EMEA/H/C/002514

EPAR summary for the public

Aubagio

teriflunomide

This is a summary of the European public assessment report (EPAR) for Aubagio. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Aubagio.

For practical information about using Aubagio, patients should read the package leaflet or contact their doctor or pharmacist.

What is Aubagio and what is it used for?

Aubagio is a medicine that contains the active substance teriflunomide. It is used to treat adults with multiple sclerosis (MS), a disease in which inflammation destroys the protective sheath around the nerves. Aubagio is used in the type of MS known as relapsing-remitting MS, when the patient has flare-ups of symptoms (relapses) followed by periods of recovery (remissions).

How is Aubagio used?

Aubagio can only be obtained with a prescription and treatment should be started and supervised by a doctor who has experience in the management of MS.

Aubagio is available as tablets (14 mg). The recommended dose is 14 mg once a day.

How does Aubagio work?

In MS, the body's immune system malfunctions and attacks parts of the central nervous system (the brain and spinal cord), causing the inflammation that damages the nerve sheaths. The active substance in Aubagio, teriflunomide, blocks an enzyme called 'dihydro-orotate dehydrogenase' which is necessary for cells to multiply. The exact way teriflunomide works in MS is not known but it is thought to reduce the number of lymphocytes which form part of the immune system and are involved in the inflammation process. With fewer lymphocytes, there is less inflammation, helping to control the symptoms of MS.

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What benefits of Aubagio have been shown in studies?

Aubagio has been studied in four main studies involving over 2,700 adults with relapsing-remitting MS.

One study involving 179 patients compared the effects of Aubagio with placebo (a dummy treatment) on the number of active lesions (developing areas of damage) in the brain detected by a brain scan. Aubagio was found to be more effective than placebo: after around 9 months (36 weeks), the number of active lesions was around 1 per scan in patients who were taking Aubagio compared with around 2.7 in patients taking placebo.

Two studies involving 2,257 patients compared the effects of Aubagio with placebo in reducing the number of relapses per patient per year (called the 'annualised relapse rate'). Treatment lasted for up to about three years (152 weeks). Aubagio was found to be more effective than placebo: in patients taking Aubagio, relapses were reduced by around 30% more than in patients taking placebo (the annualised relapse rate was 0.35 for Aubagio compared with 0.53 for placebo). The studies also looked at the effect of Aubagio on the changes in the patients' level of disability and showed that the risk of disability getting worse was reduced by 30% in comparison with placebo after around two and a half years (132 weeks) of treatment.

The fourth study involving 324 patients compared the effects of Aubagio with interferon beta-1a (another treatment for MS) on the rate of treatment failure, by looking at the time until patients had their first relapse or permanently stopped their treatment. The study lasted for up to two years. The results of the study were inconclusive. A 13.5% rate of permanent discontinuation was seen in patients taking Aubagio, compared with 24% in patients taking interferon beta-1a. However, the rate of relapse was 23.4% with Aubagio compared with 15.4% with interferon beta-1a. Overall, no conclusion could be reached from this study on any differences between Aubagio and interferon beta-1a for MS treatment.

What are the risks associated with Aubagio?

The most commonly reported side effects with Aubagio (which may affect more than 1 in 10 people) are headache, diarrhoea, increased liver enzymes, nausea (feeling sick), and alopecia (hair loss). In general, headache, diarrhoea, nausea and alopecia are mild to moderate, resolve with time and do not usually lead to treatment being stopped. For the full list of all side effects reported with Aubagio, see the package leaflet.

Aubagio must not be used in patients with:

•    severe liver disease;

•    severe immunodeficiency states, such as acquired immune deficiency syndrome (AIDS);

•    poor bone marrow function or low blood cell counts (red cells, white cells or platelets);

•    serious infections;

•    severe kidney disease that requires dialysis;

•    severe hypoproteinaemia (low blood protein levels).

Aubagio must also not be used in pregnant women or during breast-feeding. Women who can become pregnant must not take Aubagio without using reliable contraceptive measures. For the full list of restrictions, see the package leaflet.

Why is Aubagio approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Aubagio's benefits are greater than its risks and recommended that it be approved for use in the EU. In studies, Aubagio was shown to reduce relapses and delay the progression of disability in patients with relapsing-remitting MS. Although the effects were modest, they were considered to be significant and similar to other MS treatments, although there were no conclusive results available from a direct comparison with interferon beta-1a. Aubagio is given by mouth which was considered to be an advantage over other medicines such as interferon beta-1a. Regarding its safety, side effects were similar to the immunosuppressant leflunomide, as leflunomide is converted into teriflunomide in the body. The risk of serious side effects affecting the liver and bone marrow was considered manageable and adequately addressed by risk minimisation measures.

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

A risk management plan has been developed to ensure that Aubagio 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 Aubagio, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Aubagio must ensure that all healthcare professionals who are expected to use Aubagio receive an information pack containing important safety information, including the tests and monitoring that should be carried out in patients before and after starting treatment. The pack will also include information on a registry the company will set up to collect data on babies born to women treated with Aubagio, as well as a patient reminder card with key safety information for patients.

Other information about Aubagio

The European Commission granted a marketing authorisation valid throughout the European Union for Aubagio on 26 August 2013.

The full EPAR for Aubagio 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 Aubagio, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 11-2015.

Aubagio

EMA/752274/2015

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