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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/349589/2011

EMEA/H/C/000603

EPAR summary for the public

Tysabri

natalizumab

This document is a summary of the European public assessment report (EPAR) for Tysabri. 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 Tysabri.

What is Tysabri?

Tysabri is a concentrate that is made up into a solution for infusion (drip) into a vein. It contains the active substance natalizumab.

What is Tysabri used for?

Tysabri is used to treat adults with highly active multiple sclerosis (MS). MS is a disease of the nerves, in which inflammation destroys the protective sheath surrounding the nerve cells. Tysabri is used in the type of MS known as 'relapsing-remitting' MS, when the patient has attacks (relapses) in between periods with no symptoms (remissions). It is used when the disease remains active despite appropriate treatment with at least one other disease-modifying therapy, or in patients whose disease is severe and getting worse rapidly.

The medicine can only be obtained with a prescription.

How is Tysabri used?

Treatment with Tysabri should be started and continuously supervised by a doctor who is experienced in treating diseases of the nervous system and has access to a magnetic resonance imaging (MRI) scanner. This scanner will enable the doctor to see inside the body to check for changes in the brain or spinal cord linked to MS or the brain infection called progressive multifocal leukoencephalopathy (PML) which has been associated with Tysabri and other MS medicines.

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Tysabri is given as a one-hour infusion every four weeks. Because the infusion can trigger an allergic reaction, the patient must be monitored during the infusion and for one hour afterwards. If there is no clear benefit for the patient after six months, the doctor will have to re-assess the treatment.

How does Tysabri work?

The active substance in Tysabri, natalizumab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) that is found on certain cells in the body. Natalizumab has been designed to attach to a specific part of an 'integrin' called 'a4pi integrin'. This is found on the surface of most leucocytes (the white cells in the blood that are involved in the inflammation process). By attaching to integrin, natalizumab is thought to stop the leucocytes from going from the blood into the brain. This reduces inflammation, and the nerve damage caused by MS.

How has Tysabri been studied?

Tysabri has been investigated in two studies, both lasting two years. One study compared Tysabri on its own with placebo (a dummy treatment) in 942 patients. The second study compared the effect of Tysabri with that of placebo when added to interferon beta-1a in 1,171 patients. In addition, a third study is ongoing in 5,623 patients where previous treatment with another disease-modifying therapy had failed (glatiramer acetate, beta-interferon or fingolimod). In this study, Tysabri is not compared with any other treatment. Effectiveness was measured based on the number of relapses, and the changes in the patients' level of disability measured using a standard scale (the Expanded Disability Status Scale).

What benefit has Tysabri shown during the studies?

Tysabri used on its own was more effective than placebo in reducing the number of relapses. After a year, there was a decrease of about two-thirds in the number of MS attacks in Tysabri-treated patients, in comparison with the patients who received placebo. Tysabri was also more effective than placebo on the disabling effects of MS: over two years, the risk of disability getting worse was reduced by 42% in comparison with placebo. In the add-on study with interferon beta-1a, the risk of disability getting worse and the number of relapses were reduced, but the way the study was designed did not allow the clear identification of whether these results were due to Tysabri only or to the combination.

Results available from the third study so far show that there was a decrease from 1.99 MS attacks per year to 0.22 in Tysabri-treated patients regardless of which type of disease-modifying treatment they had previously used. This response was maintained for up to 5 years.

What is the risk associated with Tysabri?

Patients, carers and doctors need to be aware that Tysabri can be associated with infections, including the brain infection PML. PML has symptoms that may be similar to those of an MS attack, and can lead to severe disability or death. The risk of PML increases the longer a patient has been receiving Tysabri, especially in patients treated for more than two years. The risk of PML is also higher if the patient used immunosuppressant medicines before starting Tysabri, or if the patient has antibodies against the virus that causes PML. If PML is suspected, the doctor must stop treatment until it is certain that the patient does not have the infection.

Tysabri

EMA/405337/2016

In studies, the most common side effects with Tysabri (seen in between 1 and 10 patients in 100) were urinary tract infection (infection of the structures that carry urine), nasopharyngitis (inflammation of the nose and throat), urticaria (itchy rash), headache, dizziness, vomiting, nausea (feeling sick), arthralgia (joint pain), rigors (shaking chills), pyrexia (fever) and fatigue (tiredness). For the full list of all side effects reported with Tysabri, see the package leaflet.

About 6% of the patients in the studies developed long-lasting antibodies against natalizumab. This led to a decrease in the effectiveness of the medicine.

Tysabri must not be given to patients who have PML or who are at risk of getting an infection, including patients whose immune systems are weakened. It must not be given in combination with other disease-modifying medicines, to patients who have cancer (unless it is a type of skin cancer called basal cell carcinoma) or to patients who are under 18 years of age.

Why has Tysabri been approved?

The CHMP concluded that the effectiveness of Tysabri in MS had been clearly shown but because of its safety profile, it should only be used in patients who have a real need for the medicine either because their disease has failed to respond to a disease-modifying therapy or is getting rapidly worse. The Committee decided that Tysabri's benefits are greater than its risks and recommended that it be given marketing authorisation.

What measures are being taken to ensure the safe use of Tysabri?

The company that makes Tysabri will agree on measures to further enhance the monitoring of patients with each Member State, such as registries and studies of patients receiving Tysabri. It will also supply all doctors in each Member State who prescribe Tysabri with an educational pack that includes information on the safety of Tysabri, including information on which patients may be at a higher or lower risk of PML. The pack will also include information about the risks of this medicine for patients. Patients should receive this information when starting Tysabri, when continuing treatment for longer than 2 years, and when stopping treatment, as the risk of PML persists for 6 months after stopping treatment.

Patients who receive Tysabri must be given a special alert card that summarises the key safety information about the medicine. Patients should show this card to their partner or carer, as well as to other doctors treating them, because they may notice symptoms of PML that the patient is not aware of, such as changes in mood, behaviour or speech.

Recommendations and precautions to be followed by healthcare professionals and patients to support the safe and effective use of Tysabri have also been included in the summary of product characteristics and the package leaflet.

Other information about Tysabri:

The European Commission granted a marketing authorisation valid throughout the European Union for Tysabri on 27 June 2006.

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

This summary was last updated in 07-2016.

Tysabri

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