Vidaza Receives Expanded FDA Approval

Vidaza Receives Expanded FDA Approval to Include Overall Survival in Higher-Risk MDS

SUMMIT, N.J.--(BUSINESS WIRE)--Aug 21, 2008 - Celgene Corporation today announced Vidaza (azacitidine) received expanded U.S. Food and Drug Administration (FDA) approval to reflect new overall survival achieved in the AZA-001 survival study of patients with higher-risk myelodysplastic syndromes (MDS). This expanded indication supplements the 2004 FDA authorization of Vidaza as the first therapy approved in the U.S. for the treatment of patients with all five French American British (FAB) subtypes of MDS. Vidaza is also the first and only drug to show a statistically significant and clinically meaningful extension of survival in higher-risk MDS patients.

"The overall survival detailed in the expanded FDA approval of Vidaza is extremely important for patients with higher-risk MDS, a group with limited options and median survival of about 15 months with classical treatments," said Pierre Fenaux, M.D., Ph.D. of the Universite of Paris and lead investigator of the AZA-011 survival trial. "Vidaza, however, is also effective across a broad range of MDS subgroups, including WHO-classified AML patients, the largest subgroup in our study."

The approval is based upon the significant improvement in overall survival achieved in the Vidaza survival trial (AZA-001), the largest, international randomized Phase III controlled study ever conducted in higher-risk MDS. The median overall survival for patients treated with Vidaza in the study was 24.5 months compared to 15 months for conventional care regimens (CCR), demonstrating a survival benefit of over 9 additional months with a stratified log-rank p-value of 0.0001. The hazard ratio describing this treatment effect was 0.58 (95 percent confidence interval of 0.43 to 0.77). The extension of survival was seen across the relevant patient subgroups including those greater than 65 years, as well as poorer prognostic groups such as those with World Health Organization (WHO) classified acute myelogenous leukemia (AML), which formed 31 percent of the enrolled patients, and patients with poor risk cytogenics. In the trial, the two-year survival rate for patients with higher-risk MDS treated with Vidaza was almost doubled with 50.8 percent compared to 26.2 percent for CCR. Patients treated with Vidaza received treatment for a median of nine cycles.

"The clinical data from this randomized Phase III controlled study demonstrated that patients with higher-risk MDS treated with Vidaza benefit from a significant survival advantage, a critical measure of a drug's effectiveness," said Lewis Silverman, M.D., of the Mount Sinai Medical Center in New York City. Dr. Silverman was the lead author and Principal Investigator for the original Vidaza approval study (CALGB 9221) and an author and investigator of the international AZA-001 survival trial. "Additionally, the efficacy and safety profile of Vidaza allows for long-term therapy in patients with higher-risk MDS, underscoring the ability to treat until disease progression for optimal survival benefit."

In the AZA-001 study, the most commonly occurring adverse reactions for patients with higher-risk MDS receiving Vidaza were thrombocytopenia (69.7%), neutropenia (65.7%) and anemia (51.4%).

"This decision by the FDA reflects the unprecedented survival advantage demonstrated by Vidaza in patients with higher risk MDS," said Mohamad A. Hussein, M.D., Global Head, Medical Affairs, Hematology of Celgene, formerly of the H. Lee Moffitt Cancer Center and Research Institute. "Vidaza is another example of Celgene developing novel therapies for critical blood diseases that are enabling patients to live for years, rather than weeks and months. Today's decision strengthens our Company's ability to deliver Vidaza and our other therapies to patients in need around the world."

Important Safety Information

-- Vidaza is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol and in patients with advanced malignant hepatic tumors.

-- In Study 1 (a randomized, open-label, controlled trial carried out in 53 U.S. sites compared the safety and efficacy of subcutaneous Vidaza plus supportive care with supportive care alone ("observation") in patients with any of the five FAB subtypes of myelodysplastic syndromes (MDS)) and Study 2 (a multi-center, open-label, single-arm study of 72 patients with RAEB, RAEB-T, CMMoL, or AML), the most commonly occurring adverse reactions by SC route were nausea (70.5%), anemia (69.5%), thrombocytopenia (65.5%), vomiting (54.1%), pyrexia (51.8%), leukopenia (48.2%), diarrhea (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 AZA-001 survival trial), the most commonly occurring adverse reactions were thrombocytopenia (69.7%), neutropenia (65.7%), anemia (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%), anemia (13.7%) and febrile neutropenia (12.6%).

-- Because treatment with Vidaza is associated with anemia, 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 preexisting 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 discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.

About Vidaza

In May 2004, Vidaza became the first drug approved by the FDA for the treatment of patients with Myelodysplastic Syndromes (MDS). The FDA approved Vidaza, the first in a new class of drugs called demethylation agents, for treatment of all five MDS subtypes, which include both low-risk and high-risk patients. These MDS FAB subtypes include according to the French American British (FAB classification: refractory anemia (RA) or 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 leukemia (CMMoL).

About Epigenetics

Vidaza is an epigenetic compound believed to exert antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of Vidaza required for maximum inhibition of DNA methylation in-vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. 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 for IV administration in January 2007.

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of hematologic malignancies that affect approximately 300,000 people worldwide. Myelodysplastic syndromes occur when blood cells remain in an immature or "blast" stage within the bone marrow and never develop into mature cells capable of performing their necessary functions. Eventually, the bone marrow may be filled with blast cells suppressing normal cell development. According to the American Cancer Society, 10,000 to 20,000 new cases of MDS are diagnosed each year in the United States. Patients with higher risk MDS have a median survival of only approximately 6-12 months. MDS patients must often rely on blood transfusions to manage symptoms of anemia and fatigue and may develop life-threatening iron overload and/or toxicity from frequent transfusions, thus underscoring the critical need for new therapies targeting the cause of the condition rather than simply managing its symptoms.

About Celgene

Celgene Corporation, based in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at www.celgene.com.

This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports.

Contact

Celgene Corporation
David Gryska, 908-673-9059
Sr. Vice President and Chief Financial Officer
OR
Brian P. Gill, 908-673-9530
Vice President,
Corporate Communications

Posted: August 2008

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Vidaza (azacitidine) FDA Approval History

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