This account is pending registration confirmation. Please click on the link within the confirmation email previously sent you to complete registration. Need a new registration confirmation email? Click here
SOUTH SAN FRANCISCO, Calif., Dec. 10, 2012 (GLOBE NEWSWIRE) -- OXiGENE, Inc. (Nasdaq:OXGN), a clinical-stage biopharmaceutical company developing novel therapeutics to treat cancer, announced today that investigators at the University of Florida presented encouraging clinical data using OXiGENE's vascular disrupting agent (VDA), OXi4503, in patients with acute myelogenous leukemia (AML) at the 2012 annual meeting of the American Society of Hematology in Atlanta, Georgia. The data showed responses and a manageable safety profile in this first-in-man trial of a VDA in AML.
The clinical data were presented as an online abstract from an investigator-sponsored Phase 1 study of OXi4503, which is supported in part by the Leukemia & Lymphoma Society, for the treatment of patients with AML or myelodysplastic syndrome (MDS). The ongoing open-label, dose-escalating study is evaluating the safety profile, maximum tolerated dose (MTD) and biologic activity of OXi4503. Results were presented on 5 patients with refractory AML enrolled between May, 2011 and August, 2012. The median number of prior therapies was 4 (range, 1-7). Two subjects were assigned to the 2.5 mg/m
2 dosing cohort, 2 received 3.75 mg/m
2 and 1 received 5 mg/m
2. None of these patients developed dose-limiting toxicities. Adverse events attributable to OXi4503 infusion included bone pain, fever, anemia and thrombocytopenia. Hypertension was manageable and plasma LDH and uric acid increased by at least two-fold within hours after OXi4503 infusions, suggesting leukemia cell destruction.
Overall response was 2/5 (40%), with 1 patient achieving a marrow complete remission (mCR) and 1 patient achieving a partial remission (PR). The median number of cycles was 1 (range 1-6). Three of 5 subjects discontinued the study due to AML progression and one due to pneumonia. One patient with AML treated with 5 mg/m
2 OXi4503 has received 6 months of treatment and continues to receive weekly infusions.
To further elucidate the mechanism of AML regression by combretastatins, investigators at the University of Florida also presented preclinical data in a poster presentation titled "Vascular Disrupting Combretastatins Impair Bone Marrow Endothelial Cells by Depolymerizing the Microtubule Cytoskeleton." In this study, bone marrow endothelial cells (BMECs) from both healthy subjects and patients with AML were treated with various doses of the combretastatins OXi4503 and ZYBRESTAT® for 24 and 48 hours. The results showed that both combretastatins impaired BMECs migration and function compared to untreated control. In addition, there was a distinct degradation of microtubule cytoskeleton in BMECs treated with the two combretastatins. AML cells co-cultured with BMECs treated with the two combretastatins showed a lower survival rate than AML cells alone. Conclusions were that combretastatins directly impair BMEC function and eliminate BMEC protection of AML cells, and the dual targeting of combretastatins on BMECs and AML cells leads to enhanced AML regression.