Active Substance: obinutuzumab
Common Name: obinutuzumab
ATC Code: L01XC15
Marketing Authorisation Holder: Roche Registration Ltd
Active Substance: obinutuzumab
Authorisation Date: 2014-07-23
Therapeutic Area: Leukemia, Lymphocytic, Chronic, B-Cell
Pharmacotherapeutic Group: Antineoplastic agents
Chronic Lymphocytic Leukaemia (CLL)
Gazyvaro in combination with chlorambucil is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) and with comorbidities making them unsuitable for full-dose fludarabine based therapy (see section 5.1).
Follicular Lymphoma (FL)
Gazyvaro in combination with chemotherapy, followed by Gazyvaro maintenance therapy in patients achieving a response, is indicated for the treatment of patients with previously untreated advanced follicular lymphoma.
Gazyvaro in combination with bendamustine followed by Gazyvaro maintenance is indicated for the treatment of patients with follicular lymphoma (FL) who did not respond or who progressed during or up to 6 months after treatment with rituximab or a rituximab-containing regimen.
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 cell. Gazyvaro is used together with chlorambucil (another cancer 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 chemotherapy (other cancer medicines) in patients who have not had previous treatment for advanced FL. It is also used with the medicine bendamustine in patients whose disease has not responded to treatment involving the medicine rituximab or whose cancer has progressed during or up to 6 months after such treatment. Once the disease has responded to treatment, 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.
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 or eight cycles and each cycle lasts 21 or 28 days.
For CLL, 28-day cycles are used. 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 to the first 100 mg dose, 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 FL, Gazyvaro is given at a dose of 1,000 mg on day 1, 8 and 15 of the first 21 or 28-day treatment cycle. For the remaining cycles, the dose is given on day one only. Patients who respond to treatment, may continue to receive Gazyvaro once every two months for up to two years,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 previously untreated patients 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 was shown to be of benefit in one main study involving 1,202 patients with previously untreated FL. The study compared Gazyvaro plus other chemotherapy medicines with rituximab plus other chemotherapy medicines, and over a follow-up period of about three years on average, 17% (101 of 601 patients) given Gazyvaro died or their disease got worse, whereas 24% (144 of 601 patients) given rituximab died or their disease got worse.
Gazyvaro has also been investigated in a study involving 321 patients with FL 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 throat and nose infections), pneumonia (lung infection), urinary tract infections, cold sores, coughs, diarrhoea, constipation, joint and back pain, headache, insomnia, hair loss, itching, fever, weakness, neutropenia and leucopenia (low white blood cell counts), thrombocytopenia (low blood platelet counts), anaemia (low red blood cell counts), lymph node pain and reactions related to the infusion (which may include vomiting, dizziness, breathing difficulties, flushing, changes in blood pressure and rapid heart rate). For the full list of all side effects and restrictions, see the package leaflet.
Why is Gazyvaro approved?
The European Medicines Agency decided that Gazyvaro’s benefits are greater than its risks and recommended that it be approved for use in the European Union (EU). The Agency 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.
For more information about treatment with Gazyvaro, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.