In a statement issued today the National Institute for Health and Clinical Excellence (NICE) released a Final Appraisal Determination (FAD) recommending azacitidine (Vidaza?, Celgene International S?rl), 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 azacitidine, as an innovative, life-extending therapy, is a cost-effective use of National Health Service (NHS) resources.

Myelodysplastic syndromes (MDS) are a group of bone marrow disorders, where the marrow doesn’t produce enough of one or more types of blood cells. The majority of patients with MDS receive best supportive care in current clinical practice and some patients receive low dose chemotherapy. There are approximately 700 patients with MDS in England and Wales.

Commenting on the release, Dr Carole Longson, Health Technology Evaluation Centre Director at NICE said: “Azacitidine is the first drug that has been developed specifically for treating myelodysplastic syndromes. It is not a cure, but it does have the potential to extend patients’ lives by an average of nine months. It is a very expensive drug, but the manufacturers have submitted a patient access scheme where the cost will be reduced. We are therefore very pleased to be able to recommend azacitidine as a cost effective use of 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, Chief Executive Officer of Celgene Corporation.

What happens next
The FAD issued today 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 azacitidine extended the lives of patients with MDS by more than nine months compared to conventional care regimens.

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Regulatory approval
In December 2008, azacitidine 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 U.S. FDA also included this extension of overall survival in its approved azacitidine 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 anemia (RA), Refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia, or thrombocytopenia or requiring transfusions, Refractory anemia with excess blasts (RAEB), Refractory anemia 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. Azacitidine has received orphan drug designation in several markets including the European Union, the U.S. and Japan.

Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and cytotoxicity of abnormal hematopoietic 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 azacitidine 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 azacitidine. Azacitidine was approved by FDA for IV administration in January 2007.

For more information:
Summary of Product Characteristics (Europe)
Full Prescribtion Information (USA)
NICE (UK) Consults Again And Does Not Recommend Azacitidine For The Treatment Of Myelodysplastic Syndromes
Public summary of positive opinion for orphan designation of azacitidine for the treatment of myelodysplastic syndromes

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