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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/467814/2016

EMEA/H/C/001109

EPAR summary for the public

Ilaris

canakinumab

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

What is Ilaris?

Ilaris is a medicine that contains the active substance canakinumab. It is available as a powder

(150 mg) that is made up into a solution for injection.

What is Ilaris used for?

Ilaris is used to treat:

•    cryopyrin-associated periodic syndromes (CAPS) in adults and children aged two years and older with a body weight of 7.5 kg or above. CAPS are a group of diseases where patients have a defect in the gene that produces a protein called cryopyrin. This leads to inflammation in many parts of the body, with symptoms such as fever, rash, joint pain and tiredness. Severe disabilities such as deafness and loss of vision may also occur.

•    Still's disease, including adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA), rare diseases causing inflammation of joints as well as rash and fever. Ilaris can be used in patients aged two years and older who have active disease and have not responded adequately to medicines called non-steroidal anti-inflammatory drugs (NSAIDs) and systemic corticosteroids. Ilaris is used on its own or in combination with methotrexate (a medicine that acts on the immune system).

•    gouty arthritis (painful inflammation of the joints caused by deposit of urate crystals). Ilaris is used to treat the symptoms in adults with frequent attacks of gouty arthritis (at least three in the

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previous 12 months). It is used when NSAIDs and another medicine, colchicine, cannot be used or do not work adequately, and when repeated treatment with corticosteroids is not appropriate.

The medicine can only be obtained with a prescription.

How is Ilaris used?

In CAPS and Still's disease, treatment with Ilaris should be started and supervised by a specialist doctor experienced in diagnosing and treating these conditions. In CAPS, the recommended dose depends on the patient's bodyweight and age and is given as an injection under the skin every eight weeks. The doctor may adjust the dose depending on how patients respond to treatment. In Still's disease, patients with a body weight of 7.5 kg or above are given 4 mg per kilogram body weight (up to a maximum dose of 300 mg) as an injection under the skin every four weeks. Patients with CAPS and Still's disease (or their carers) may inject Ilaris once they have been trained if their doctor believes it is appropriate.

In gouty arthritis, treatment with Ilaris should be started and supervised by a specialist doctor experienced in diagnosing and treating gouty arthritis and in the use of biological medicines. Ilaris should be given by a healthcare professional as an on-demand therapy to treat gouty arthritis attacks. Patients should also receive appropriate treatment to control uric acid levels in the blood. The recommended dose is 150 mg given as a single injection under the skin as soon as possible after the start of an attack. For patients who require further doses, there should be an interval of at least 12 weeks between two doses of Ilaris.

How does Ilaris work?

The active substance in Ilaris, canakinumab, is a monoclonal 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. Canakinumab has been designed to attach to a messenger molecule or 'cytokine' in the body called interleukin-1 beta. This messenger is involved in causing inflammation and is found in high levels in patients with CAPS, Still's disease and gouty arthritis. By attaching to interleukin-1 beta, canakinumab blocks its activity, helping to reduce inflammation thereby relieving the symptoms of the diseases.

How has Ilaris been studied?

In CAPS, Ilaris has been studied in three main studies involving 220 adults and children 2 years and older. The first study involved 35 patients who were given one injection of Ilaris which was repeated after eight weeks. Patients who responded to treatment were then given either Ilaris or placebo (a dummy treatment) every eight weeks for the next 24 weeks. In the following 16 weeks, all patients received Ilaris every eight weeks. In the other two studies, 185 patients with CAPS (including seven children aged 2-4 years) were given Ilaris every eight weeks for at least 24 weeks. In all three studies, the main measure of effectiveness was the number of patients who did not have a 'disease flare' (relapse of symptoms) after a 24-week treatment period.

In SJIA, Ilaris has been studied in two main studies. The first study compared Ilaris with placebo in 84 patients aged from 2 to 20 years. The main measure of effectiveness was based on the reduction in symptoms of arthritis 15 days after treatment, as assessed using standard criteria. The second study involved 177 patients aged from 2 to 20 years and had two parts: in the first part, all patients were given an injection of Ilaris every four weeks for a maximum of 32 weeks. The aim of this part of the study was to assess whether treatment with Ilaris allowed a reduction in the use of steroids in at least a quarter of patients. One hundred patients then entered the second part of the study, which compared Ilaris with placebo. The main measure of effectiveness was based on the time to disease flare. To support the use of Ilaris in AOSD, the company submitted further analyses of the data from the SIJA studies and data from the published literature comparing the disease processes of AOSD and SIJA.

In gouty arthritis, Ilaris was studied in two main studies involving 454 patients who were given either Ilaris or another anti-inflammatory medicine (triamcinolone acetonide) for 12 weeks. The main measures of effectiveness were pain intensity (measured on a scale from 0 to 100) 3 days after taking the medicine, as well as the time to a first new attack of gouty arthritis.

What benefit has Ilaris shown during the studies?

In CAPS, Ilaris was more effective than placebo. In the first study, none of the 15 patients with CAPS who received Ilaris during the 24-week treatment period had a 'disease flare', compared with 81% of patients who received placebo (13 out of 16). In the other two studies, 85% of patients had no relapses. This percentage was lower for children aged 2 to 4 years, with around 57% of them being free of disease flares after 24 weeks.

In SJIA, the first study showed that Ilaris was more effective than placebo at reducing symptoms of arthritis: around 84% of patients who received Ilaris achieved the required reduction in symptoms (36 out of 43), compared with about 10% of patients who received placebo (4 out of 41). In the first part of the second study, around 45% of the patients who were taking steroids at the beginning of the study were able to reduce their dose of steroids (57 out of 128). In the second part, the risk of experiencing a disease flare was reduced by 64% with Ilaris, compared with placebo. Further analyses of these data, together with data from the published literature, showed that SIJA and AOSD share common features and that the effects of Ilaris in AOSD patients are expected to be similar to the effects seen in SIJA patients

In gouty arthritis, both studies showed that Ilaris was more effective than triamcinolone acetonide at reducing pain intensity. In patients taking Ilaris the pain was reduced from 74 to 25 units, whereas in patients taking the comparator the pain was reduced from 74 to 35 units. The risk of developing a new gouty arthritis attack was also reduced with Ilaris (17% with Ilaris versus 37% with triamcinolone acetonide).

What is the risk associated with Ilaris?

Serious infections have been observed in patients taking Ilaris. The most common side effects with Ilaris are infections, generally mild to moderate, of the upper respiratory tract (colds). For the full list of all side effects reported with Ilaris, see the package leaflet.

Ilaris must not be used in patients with active or severe infection. For the full list of restrictions, see the package leaflet.

Why has Ilaris been approved?

The CHMP decided that Ilaris's benefits are greater than its risks and recommended that it be given marketing authorisation.

Ilaris has been authorised under 'exceptional circumstances'. This means that because CAPS is a rare disease, it has not been possible to obtain complete information about Ilaris. Every year, the European

Medicines Agency will review any new information that may become available and this summary will be updated as necessary.

What information is still awaited for Ilaris?

The company that markets Ilaris will provide regular information on the long-term safety and effectiveness of Ilaris in adults and children suffering from CAPS. This information comes from a registry and will further investigate what happens to the medicine in the body, especially in children.

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

The company that markets Ilaris will provide doctors who will use Ilaris with educational material containing the prescribing information, the patient alert card and information for doctors containing important safety information about Ilaris, including precautions to be taken when using the medicine.

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

Other information about Ilaris

The European Commission granted a marketing authorisation valid throughout the European Union for Ilaris on 23 October 2009.

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

This summary was last updated in 07-2016.

Ilaris

EMA/467814/2016

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