Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation announced that the National Institute for Health and Clinical Excellence (NICE) has issued a Final Appraisal Determination (FAD) recommending Vidaza within its licensed indication, as an option for the treatment of patients in England and Wales with Myelodysplastic Syndromes (MDS) and acute myeloid leukaemia. NICE determined that Vidaza, as an innovative, life-extending therapy, is a cost-effective use of National Health Service (NHS) resources.
“We applaud the positive FAD from NICE that will provide patients more widespread access to a therapy that has been shown to prolong survival in these incurable blood cancers,” said Robert J. Hugin, CEO of Celgene Corporation.
The FAD issued has been sent to the appraisal consultees who may appeal the decision within 15 days. If there is no appeal, NICE may use the FAD to form the basis of its final guidance to the NHS, expected in the first half of 2011.
NICE's evaluation considered peer-reviewed clinical studies that demonstrated Vidaza extended the lives of patients with MDS by more than nine months compared to conventional care regimens.
In December 2008, Vidaza became the first and only drug approved by the European Commission to demonstrate a significant extension of overall survival compared to conventional care regimens, for patients with Intermediate-2 and high-risk MDS and AML (20-30% blasts). Earlier in 2008 the US FDA also included this extension of overall survival in its approved Vidaza indication for treatment of all five French, American, British (FAB) MDS subtypes, which includes both low-risk and high-risk patients.
These subtypes include: refractory anaemia (RA), Refractory Anaemia with Ringed Sideroblasts (RARS) if accompanied by neutropenia, or thrombocytopenia or requiring transfusions, Refractory Anaemia with Excess Blasts (RAEB), Refractory Anaemia with Excess Blasts in Transformation (RAEB-T), and Chronic Myelomonocytic Leukaemia (CMML). The more recent WHO classification system incorporates RAEB-T patients within the AML category. Vidaza has received orphan drug designation in several markets including the European Union, the US and Japan.
Vidaza is believed to exert its antineoplastic effects by causing hypomethylation of DNA and cytotoxicity of abnormal haematopoietic cells in the bone marrow. DNA hypomethylation of aberrantly methylated genes involved in normal cell cycle regulation, differentiation and death pathways may result in gene re-expression and restoration of cancer-suppressing functions to cancer cells.
The cytotoxic effects of Vidaza cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to Vidaza. Vidaza was approved by FDA for IV administration in January 2007.
Vidaza is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol and in patients with advanced malignant hepatic tumours. In Studies 1 and 2, the most commonly occurring adverse reactions by SC route were nausea (70.5%), anaemia (69.5%), thrombocytopenia (65.5%), vomiting (54.1%), pyrexia (51.8%), leukopenia (48.2%), diarrhoea (36.4%), injection site erythema (35.0%), constipation (33.6%), neutropenia (32.3%), and ecchymosis (30.5%). Other adverse reactions included dizziness (18.6%), chest pain (16.4%), febrile neutropenia (16.4%), myalgia (15.9%), injection site reaction (13.6%), and malaise (10.9%). In Study 3, the most common adverse reactions by IV route also included petechiae (45.8%), weakness (35.4%), rigors (35.4%), and hypokalemia (31.3%).
In Study 4, the most commonly occurring adverse reactions were thrombocytopenia (69.7%), neutropenia (65.7%), anaemia (51.4%), constipation (50.3%), nausea (48.0%), injection site erythema (42.9%), and pyrexia (30.3%). The most commonly occurring Grade 3/4 adverse reactions were neutropenia (61.1%), thrombocytopenia (58.3%), leukopenia (14.9%), anaemia (13.7%), and febrile neutropenia (12.6%). Because treatment with Vidaza is associated with anaemia, neutropenia, and thrombocytopenia, complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle. Because azacitidine is potentially hepatotoxic in patients with severe pre-existing hepatic impairment, caution is needed in patients with liver disease.
In addition, azacitidine and its metabolites are substantially excreted by the kidneys and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function. Vidaza may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be apprised of the potential hazard to the fetus. Men should be advised not to father a child while receiving Vidaza. Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother
Celgene International Sàrl, is a wholly owned subsidiary and international headquarters of Celgene Corporation is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation.