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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/338198/2016

EMEA/H/C/002799

EPAR summary for the public

Gazyvaro

obinutuzumab

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

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

What is Gazyvaro and what is it used for?

Gazyvaro is a cancer medicine used to treat adult patients with:

•    previously untreated chronic lymphocytic leukaemia (CLL). CLL is a cancer of B-lymphocytes, a type of white blood cells. Gazyvaro is used together with chlorambucil (a cancer chemotherapy medicine) in patients for whom the cancer medicine fludarabine is not recommended;

•    follicular lymphoma (FL), another type of cancer of B-lymphocytes. Gazyvaro is used together with the chemotherapy medicine bendamustine in patients whose disease has not responded or whose cancer hasprogressed during or up to 6 months after treatment with the medicine rituximab. Following treatment with bendamustine Gazyvaro is then used on its own for the maintenance treatment of FL.

Gazyvaro contains the active substance obinutuzumab.

Because the number of patients with CLL and with FL is low, the diseases are considered 'rare', and

Gazyvaro was designated an 'orphan medicine' (a medicine used in rare diseases) on 10 October 2012

and 19 June 2015.

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How is Gazyvaro used?

Gazyvaro can only be obtained with a prescription and treatment should be given under the close supervision of an experienced doctor. As serious side effects including allergic reactions can develop treatment should be given in facilities where these reactions can be treated appropriately.

Gazyvaro is available as a concentrate that is made up into a solution for infusion (drip) into a vein and given over several hours. Treatment with Gazyvaro is given in six cycles and each cycle lasts 28 days.

For CLL, a dose of 100 mg of Gazyvaro is given on day one of the first cycle under close supervision of an experienced doctor who should monitor the patient for infusion-related reactions. A second dose of 900 mg can be given on the same day, if the patient does not have any reactions. In case of infusion-related reactions the second dose should be delayed until day 2. Further doses of 1,000 mg are then given on days 8 and 15 of the first cycle. For the remaining 5 cycles, Gazyvaro 1,000 mg is given on day one only.

For follicular lymphoma, Gazyvaro is given at a dose of 1,000 mg on day 1, 8 and 15 of the first 28-day treatment cycle. For the remaining 5 cycles, Gazyvaro 1,000 mg is given on day one only. Patients who respond to treatment, may continue to receive 1,000 mg Gazyvaro once every two months for two years or as long as they benefit from it.

Patients may also be given other medicines to prevent infusion-related reactions and other side effects. For further information, see the package leaflet.

How does Gazyvaro work?

The active substance in Gazyvaro, obinutuzumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to the protein CD20, which is found on the surface of B-lymphocytes. In CLL and FL, cancerous B-lymphocytes multiply too quickly and replace the normal cells in the bone marrow (where blood cells are made) and in lymph nodes. By attaching to CD20 on B-lymphocytes, obinutuzumab makes the B-lymphocytes a target for the body's immune (defence) system, which kills the B-lymphocytes.

What benefits of Gazyvaro have been shown in studies?

In CLL, Gazyvaro has been shown to significantly delay the disease getting worse in patients previously untreated who had other medical conditions and were therefore ineligible for fludarabine-based therapy. In one main study involving 781 patients, those treated with Gazyvaro and chlorambucil lived significantly longer on average without their disease getting worse than patients treated with chlorambucil alone (26.7 months versus 11.1 months). Similarly, patients treated with Gazyvaro and chlorambucil lived significantly longer on average without their disease getting worse than patients treated with rituximab and chlorambucil (26.7 months versus 15.2 months).

Gazyvaro has also been investigated in a study involving 321 patients with follicular lymphoma in whom treatment with rituximab had either not worked or had stopped working. Patients treated with Gazyvaro and bendamustine lived significantly longer on average without their disease getting worse than patients treated with bendamustine alone (29.2 months versus 13.7 months).

What are the risks associated with Gazyvaro?

The most common side effects with Gazyvaro (which may affect more than 1 in 10 people) are upper respiratory infections (such as throad and nose infections), coughs, diarrhoea, constipation, joint pain, fever, weakness, neutropenia (low white blood cell counts), thrombocytopenia (low blood platelet

counts) and anaemia (low red blood cell counts). For the full list of all side effects and restrictions, see the package leaflet.

Why is Gazyvaro approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Gazyvaro's benefits are greater than its risks and recommended that it be approved for use in the European Union (EU). The CHMP considered that the benefit of Gazyvaro in prolonging the survival of CLL and FL patients before their disease worsened was clearly demonstrated. The pattern of side effects was considered acceptable in the light of the medicine's benefit.

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

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

Other information about Gazyvaro

The European Commission granted a marketing authorisation valid throughout the European Union for Gazyvaro on 23 July 2014.

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

The summaries of the opinion of the Committee for Orphan Medicinal Products for Gazyvaro can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/Rare disease designation (CLL and FL).

This summary was last updated in 07-2016.

Gazyvaro

EMA/338198/2016

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