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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/430055/2011

EMEA/H/C/002213

EPAR summary for the public

Yervoy

ipilimumab

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

What is Yervoy?

Yervoy is a medicine that contains the active substance ipilimumab. It is available as a concentrate that is made up into a solution for infusion (drip) into a vein.

What is Yervoy used for?

Yervoy is used to treat adults with advanced melanoma (a type of skin cancer affecting cells called melanocytes).

The medicine can only be obtained with a prescription.

How is Yervoy used?

Treatment with Yervoy should be started and supervised by a specialist doctor experienced in treating cancer.

The doctor should carry out blood tests to check the patient's liver and thyroid function before and regularly during treatment.

Yervoy is given as an infusion into a vein over 90 minutes. The patient receives four doses in total, with three weeks between each dose. Doses may need to be delayed if certain side effects occur, and treatment may have to be stopped altogether if side effects are severe. The recommended dose for each infusion is 3 mg per kilogram body weight.

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How does Yervoy work?

The active substance in Yervoy, ipilimumab, 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 in certain cells in the body.

Ipilimumab has been designed to attach to and block the activity of a protein called CTLA-4 that is found on the surface of T cells, a type of white blood cell. CTLA-4 inhibits the activity of T cells. Ipilimumab, by blocking CTLA-4, leads to the activation and spread of the T cells, which infiltrate tumours and kill the tumour cells.

How has Yervoy been studied?

The effects of Yervoy have been looked at in two main studies. One main study involved 676 patients with advanced melanoma that had been previously treated and in whom the treatment had not worked or had stopped working. The patients received treatment with Yervoy (3 mg per kg bodyweight), treatment with an experimental medicine called 'gp100', or treatment with a combination of Yervoy and gp100. The other main study involved 502 patients with advanced melanoma that had not been previously treated. High-dose Yervoy (10 mg per kg body weight) or placebo (a dummy treatment) was added to standard treatment with dacarbazine, another cancer medicine. The main measure of effectiveness in both studies was overall survival (how long the patients lived). In addition, the company provided data from several studies comparing the overall survival of patients who had or who had not been previously treated and were given Yervoy at 3 mg per kg bodyweight.

What benefit has Yervoy shown during the studies?

Yervoy was shown to improve overall survival. In the first study, patients survived for around 10 months on treatment with Yervoy or the combination treatment, compared with 6 months on gp100 alone. In the second study, patients given Yervoy with dacarbazine survived an average of 11 months, compared with 9 months in those given placebo plus dacarbazine, but about a third of the patients given Yervoy were unable to complete treatment due to side effects. The additional data showed that previously untreated patients given Yervoy 3 mg per kg bodyweight survived for an average of 13.5 months.

What is the risk associated with Yervoy?

Yervoy is commonly associated with side effects resulting from excessive activity of the immune system, including severe reactions and inflammation. Most will resolve following appropriate treatment or on stopping Yervoy. The most common individual side effects, affecting more than 10% of patients, are diarrhoea, rash, pruritus (itching), fatigue (tiredness), nausea (feeling sick), vomiting, decreased appetite and abdominal pain (stomach ache). For the full list of all side effects reported with Yervoy, see the package leaflet.

Why has Yervoy been approved?

The CHMP noted that Yervoy has been shown to improve survival in a condition where overall survival rates are low. With regard to the medicine's side effects, the most frequent were mild to moderate in severity. The CHMP therefore decided that Yervoy's benefits are greater than its risks and recommended that it be given marketing authorisation. The CHMP recommended the use of the 3 mg per kg bodyweight dose as it is not clear whether a higher dose of Yervoy would give additional

Yervoy

benefits and a higher risk of side effects would be expected. The CHMP asked the company to conduct a study to compare the 3 and 10 mg per kg bodyweight doses directly.

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

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

In addition, the company that makes Yervoy must ensure that all healthcare professionals expected to prescribe the medicine as well as patients are provided with a brochure with safety information on the medicine including the side effects related to the excessive activity of the immune system. Patients will also receive from their doctor an alert card summarising key safety information on the medicine. The company is also obliged to complete a study comparing the effects of Yervoy in doses of 3 and 10 mg per kg bodyweight in treating advanced melanoma.

Other information about Yervoy

The European Commission granted a marketing authorisation valid throughout the European Union for Yervoy on 13 July 2011.

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

This summary was last updated in 10-2013.

Yervoy

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