The VIDAZA Marketing Authorisation has been updated to include this new indication in AML, covering patients who have > 30% myeloblasts according to the WHO classification; previously, the indication covered AML patients with < 30% blasts.
Myeloblasts are white cells in the bone marrow; in AML, their functioning is disrupted and results in numerous non-functioning white cells, which can potentially interfere with the body's ability to control infections and can lead to anaemia and haemorrhages.
For many patients, AML is typically associated with a poor prognosis
particularly for those patients who cannot tolerate potentially curative
therapies like stem cell transplantation. In
"Today's announcement brings hope to patients with AML, particularly the
elderly and more frail patients who cannot undergo intensive therapies
such as stem cell transplantation," said
In the study, grade 3-4 anaemia, neutropenia, febrile neutropenia, and thrombocytopenia rates, respectively, were 16%, 26%, 28%, and 24% with azacitidine; 5%, 5%, 28%, 5% with best supportive care; 23%, 25%, 30%, 28% with low-dose Ara-Cytarabine; and 14%, 33%, 31%, 21% with intensive chemotherapy.
Today's approval marks the fourth new product or extension of the
indication approved by the EC in the EU for
IMPORTANT SAFETY INFORMATION
Hypersensitivity to the active substance, or to any of the excipients
Advanced malignant hepatic tumours
WARNINGS AND PRECAUTIONS:
Haematological toxicity: Treatment with azacitidine is associated with anaemia, neutropenia and thrombocytopenia, particularly during the first 2 cycles. Complete blood counts should be performed to monitor response and toxicity, as required but at least prior to each treatment cycle. A dose reduction may be required. Patients should be advised to promptly report febrile episodes. Patients and physicians are also advised to be observant for signs and symptoms of bleeding.
Hepatic impairment: No formal studies have been conducted in patients with hepatic impairment. Patients with extensive tumour burden due to metastatic disease have been reported to experience progressive hepatic coma and death during azacitidine treatment, and should be carefully monitored. Azacitidine is contraindicated in patients with advanced malignant hepatic tumors.
Renal impairment: Renal abnormalities ranging from elevated serum creatinine to renal failure and death were reported in patients treated with intravenous azacitidine in combination with other chemotherapeutic agents. If unexplained reductions in serum bicarbonate ( < 20 mmol/l) or elevations of serum creatinine or BUN occur, the dose should be reduced or administration delayed. The patients should be advised to report oliguria and anuria to the health care provider immediately. Although no clinically relevant differences in the frequency of adverse reactions were noted between subjects with normal renal function compared to those with renal impairment, patients with renal impairment should be closely monitored for toxicity since azacitidine and/or its metabolites are primarily excreted by the kidney.
Laboratory tests: Liver function tests, serum creatinine and serum bicarbonate should be determined prior to initiation of therapy and prior to each treatment cycle. Complete blood counts should be performed prior to initiation of therapy and as needed to monitor response and toxicity, but at a minimum, prior to each treatment cycle.
Cardiac and pulmonary disease: Patients with a history of severe congestive heart failure, clinically unstable cardiac disease or pulmonary disease were excluded from the pivotal registration study and therefore the safety and efficacy of Vidaza in these patients has not been established. Recent data from a clinical trial in patients with a known history of cardiovascular or pulmonary disease showed a significantly increased incidence of cardiac events with Vidaza. It is therefore advised to exercise caution when prescribing Vidaza to these patients. Cardiopulmonary assessment before and during the treatment with Vidaza should be considered.
Necrotising fasciitis: Necrotising fasciitis, including fatal cases, have been reported in patients treated with Vidaza. Vidaza therapy should be discontinued in patients who develop necrotising fasciitis, and appropriate treatment should be promptly initiated.
Men and women of childbearing potential must use effective contraception during and up to 3 months after treatment. There is no adequate data on the use of azacitidine in pregnant women. Studies in mice have shown reproductive toxicity. Based on results from animal studies and its mechanism of action, azacitidine should not be used during pregnancy, especially during the first trimester unless clearly necessary. The advantages of treatment should be weighed against the possible risk for the foetus in every individual case
USE IN SPECIFIC POPULATIONS:
Pediatric population (0 - 17 years): The safety and efficacy of Vidaza in children aged 0-17 years have not yet been established. No data are available
Elderly patients: No specific dose adjustments are recommended for the elderly. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function
Renal impairment: Azacitidine can be administered to patients with renal impairment without initial dose adjustment.
Hepatic impairment: Patients with severe hepatic organ impairment should be carefully monitored for adverse events. No specific modification to the starting dose is recommended for patients with hepatic impairment prior to starting treatment; subsequent dose modifications should be based on haematology laboratory values. Vidaza is contraindicated in patients with advanced malignant hepatic tumours.
The most commonly reported adverse reactions with azacitidine treatment were haematological reactions including thrombocytopenia, neutropenia, febrile neutropenia and leukopenia (usually Grade 3-4), gastrointestinal events including nausea, vomiting, constipation and diarrhoea (usually Grade 1-2) or injection site reactions and pyrexia (usually Grade 1-2). Other side-effects seen on treatment with Vidaza are listed in the SPC.
Please refer to the Summary of Product Characteristics for full European prescribing information.
About Acute Myeloid Leukaemia
For many patients, AML is a disease that is associated with a poor
prognosis and deteriorating quality of life. AML patients tend to be
older with poor-risk features; as such, a large proportion are
ineligible for intensive but potentially curative therapies, and while
there have been some advances recently, treatment options remain
Celgene International Sàrl, located in Boudry, in the
This press release contains forward-looking statements, which are
generally statements that are not historical facts. Forward-looking
statements can be identified by the words "expects," "anticipates,"
"believes," "intends," "estimates," "plans," "will," "outlook" and
similar expressions. Forward-looking statements are based on
management's current plans, estimates, assumptions and projections, and
speak only as of the date they are made. We undertake no obligation to
update any forward-looking statement in light of new information or
future events, except as otherwise required by law. Forward-looking
statements involve inherent risks and uncertainties, most of which are
difficult to predict and are generally beyond our control. Actual
results or outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual Report
on Form 10-K and our other reports filed with the
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1 Alan K. Burnett ASH 2012 Ham-Wasserman lecture; Hematology 2012:1-6
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