Additional Analyses of High-Risk Patients from Phase III Study (AML-001) OF Vidaza® (Azacitidine for Injection) in Acute Myeloid Leukemia Presented at ASH

SAN FRANCISCO--(BUSINESS WIRE)--

Celgene Corporation CELG today announced that data from two sub-group analyses from AML-001, its phase III study of VIDAZA^® (azacitidine for injection) compared with conventional care regimens (CCR) in elderly subjects with newly diagnosed acute myeloid leukemia (AML, >30% blasts), were presented at the 56^th American Society of Hematology annual meeting.

In this global, multi-center, randomized, open-label pivotal study, patients at least 65 years old with newly diagnosed or secondary AML with >30% bone marrow blasts were pre-selected to receive one of three regimens per investigator's choice: intensive chemotherapy (IC; standard 7+3 regimen), low-dose Ara-C (LDAC; 20 mg SC twice per day for 10 days of each 28-day cycle) or best supportive care (BSC) only. Patients were then randomized to receive either azacitidine (n=241) (75 mg/m²/d SC for 7 days of each 28-day cycle) or their predetermined CCR (n=247). The sub-analyses were not powered to detect statistically significant differences.

In the first sub-analysis, Prof. Hervé Dombret reported results from the study focused on patients with AML with morphologic dysplastic changes (AML-MDC).

Of 488 patients in the AML-001 study, 158 (32.4%) had AML-MDC. In these patients, the median overall survival (OS) was twice as long in patients who received azacitidine compared with those who received CCR (12.7 months [95% CI, 7.2, 14.1] vs. 6.3 months [95% CI, 4.3, 9.6] [HR 0.69, 0.48, 0.98, p=0.0357]). The one-year survival rate for patients receiving azacitidine was also higher compared with CCR (50.7% vs. 33.8%; 95% CI, 1.5, 32.2). Rates of patients achieving a complete remission plus morphological complete response with incomplete blood count were 26.7% with azacitidine compared with 19.3% with CCR.

For patients with AML-MDC who were pre-selected to receive LDAC before randomization to azacitidine or CCR (azacitidine n=49, LDAC n=50), median OS was 13.2 months with azacitidine vs. 6.3 months in the LDAC group (HR=0.76, 95% CI, 0.49, 1.19; p=0.23). The one-year survival rate with azacitidine was 55% vs. 31% with LDAC (95% CI, 5.0, 43.0).

Grade 3-4 adverse event rates included: anemia (azacitidine 12%; IC 15%; LDAC 16%; BSC 6%), neutropenia (azacitidine 30%; IC 46%, LDAC 29%; BSC 11%), febrile neutropenia (azacitidine 30%; IC 39%; LDAC 35%; BSC 44%) and thrombocytopenia (azacitidine 28%; IC 31%; LDAC 27%; BSC 11%).

“The sub-analyses into areas of significant medical need in this study, particularly for patients with poor prognostic factors, provide insight into the safety and efficacy of azacitidine in AML-MDC,” said Professor Dombret.

In the second sub-analysis, patients were stratified by cytogenetic risk into either poor-risk (n=170) or intermediate-risk (n=315), which includes cytogenetic normal (CN) patients (n=218).

Median OS (95% CI) in poor-risk patients was significantly prolonged with azacitidine vs. CCR (6.4 months [4.2, 8.1] vs. 3.2 months [2.2, 4.7], respectively; HR=0.68 [0.50, 0.94], p=0.019). In intermediate-risk patients, median OS was 13.0 months (11.2, 16.3) with azacitidine vs. 10.1 months (7.1, 13.3) with CCR (HR=0.90 [0.70, 1.16], p=0.41). The median OS in the CN subgroup was 14.1 months (12.6, 19.5) vs. 10.0 months (6.4, 13.3), respectively (HR=0.81 [0.59, 1.10], p=0.18).

Estimated one-year survival was higher with azacitidine compared with CCR in all cytogenetic risk subgroups. Twice the proportion of azacitidine-treated patients in the poor-risk subgroup were alive at one year compared with CCR patients (30.9% vs 14.0%, respectively; 95% CI, 4.4, 29.5). In the CN subgroup, 60.7% vs. 44.1% of patients were alive at one year in the azacitidine and CCR groups, respectively. The effect on one-year survival in the INT-risk subgroup was also favorable (55.2% for azacitidine vs. 45.5% with CCR).

Grade 3-4 events included: anemia (azacitidine 16%; BSC 5%, LDAC 23%, IC 14%), neutropenia (azacitidine 26%; BSC 5%, LDAC 25%, IC 33%), febrile neutropenia (azacitidine 28%; BSC 28%, LDAC 30%, IC 31%), and thrombocytopenia (azacitidine 24%; BSC 5%, LDAC 28%, IC 21%).

VIDAZA^® is not indicated for patients with acute myeloid leukemia.

In the U.S., VIDAZA^® (azacitidine for injection) is indicated for treatment of patients with the following French-American-British (FAB) myelodysplastic syndrome subtypes: 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).

U.S. IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

• VIDAZA is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol and in patients with advanced malignant hepatic tumors

WARNINGS AND PRECAUTIONS:

Anemia, Neutropenia and Thrombocytopenia:

• 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

Severe Pre-existing Hepatic Impairment:

• Because azacitidine is potentially hepatotoxic in patients with severe preexisting hepatic impairment, caution is needed in patients with liver disease.

Renal Toxicity:

Patients with renal impairment may be at increased risk for renal toxicity. Also, azacitidine and its metabolites are primarily excreted by the kidney. Therefore, these patients should be closely monitored for toxicity

Use in Pregnancy:

• 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

USE IN SPECIFIC POPULATIONS:

Nursing Mothers:

• Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother

ADVERSE REACTIONS:

• In Studies 1 and 2, 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 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%)

Please see full Prescribing Information, including CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and ADVERSE REACTIONS.

About Celgene

Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical 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. For more information, please visit www.celgene.com. Follow us on Twitter @Celgene as well, and on Pinterest and LinkedIn.

Forward-Looking Statements

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 Securities and Exchange Commission.