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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/404277/2016

EMEA/H/C/003790

EPAR summary for the public

Kyprolis

carfilzomib

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

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

What is Kyprolis and what is it used for?

Kyprolis is a cancer medicine used together with the medicines lenalidomide and dexamethasone or with dexamethasone alone, to treat multiple myeloma (a cancer of the bone marrow). It is given to adults who have received at least one previous treatment for their cancer.

Kyprolis contains the active substance carfilzomib. Because the number of patients with multiple myeloma is low, the disease is considered 'rare', and Kyprolis was designated an 'orphan medicine' (a medicine used in rare diseases) on 3 June 2008.

How is Kyprolis used?

Kyprolis can only be obtained with a prescription and treatment must be supervised by a doctor experienced in the treatment of cancer.

Kyprolis is available as a powder to be made up into a solution for infusion (drip) into a vein. It is given in four-week treatment cycles, on days 1, 2, 8, 9, 15 and 16 of each cycle. From cycle 13 onwards, the doses on day 8 and 9 are not given if Kyprolis is used with lenalidomide and dexamethasone. The starting dose is 20 mg per square metre of body surface area (calculated using the patient's height and weight), which may be increased if the medicine is well tolerated. Each infusion may last 10 to 30

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minutes. Treatment may need to be stopped or the dose reduced, if the disease gets worse or the patient has severe side effects.

How does Kyprolis work?

The active substance in Kyprolis, carfilzomib, is a proteasome inhibitor. This means that it blocks the proteasome, which is a system within the cells that breaks down proteins when they are no longer needed. Cancer cells have an increased need to produce and break down proteins due to the fact that they are multiplying rapidly. When proteins in the cancer cells are not broken down by the proteasome, they accumulate in the cells which eventually die, slowing down the growth of the cancer.

What benefits of Kyprolis have been shown in studies?

Kyprolis taken together with lenalidomide and dexamethasone has been compared with lenalidomide plus dexamethasone in one main study involving 792 patients with multiple myeloma whose disease had got worse after previous treatment. The study showed that Kyprolis is effective at prolonging the average length of time before the patient's disease got worse again (progression-free survival): patients receiving Kyprolis plus lenalidomide and dexamethasone lived for an average of 26.3 months without their disease getting worse, compared with 17.6 months for patients receiving only lenalidomide and dexamethasone.

Another study in 929 multiple myeloma patients whose disease had got worse after previous treatment compared the combination of Kyprolis and dexamethasone with bortezomib and dexamethasone. The study showed that the combination of Kyprolis and dexamethasone is more effective at improving progression-free survival than bortezomib and dexamethasone: patients receiving Kyprolis plus dexamethasone lived for an average of 18.7 months without their disease getting worse, compared with 9.4 months for patients receiving bortezomib and dexamethasone.

What are the risks associated with Kyprolis?

The most common side effects with Kyprolis (which may affect more than 1 in 5 people) are anaemia (low red blood cell counts), tiredness, diarrhoea, thrombocytopenia (low blood platelet counts), nausea (feeling sick), fever, dyspnoea (difficulty breathing), respiratory tract (airways) infection, cough and peripheral oedema (swelling, especially of the ankles and feet).

The most serious side effects include toxic effects on the heart, lungs and liver, hypertension (high blood pressure), pulmonary hypertension (high blood pressure in the blood vessels in the lungs), dyspnoea, acute kidney failure, tumour lysis syndrome (a complication due to the breakdown of cancer cells), infusion reactions, thrombocytopenia, PRES (a brain disorder which may improve over time) and TTP/HUS (diseases characterised by problems with the blood clotting system). For the full list of all side effects reported with Kyprolis, see the package leaflet.

Kyprolis must not be used in women who are breastfeeding. For the full list of restrictions, see the package leaflet.

Why is Kyprolis approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Kyprolis' benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP noted the unmet medical need for patients with multiple myeloma who no longer respond to the available therapies. It considered that the increase in time without the disease getting worse seen with Kyprolis

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was clinically meaningful. Regarding safety, although side effects, including severe effects, were seen with treatment involving Kyprolis, these were considered acceptable and manageable.

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

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

Other information about Kyprolis

The European Commission granted a marketing authorisation valid throughout the European Union for Kyprolis on 19 November 2015.

The full EPAR and risk management plan summary for Kyprolis 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 Kyprolis, 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 Kyprolis can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/Rare disease designation.

This summary was last updated in 06-2016.

Kyprolis

EMA/404277/2016