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news.Sunesis Pharmaceuticals (Sunesis) has published new nonclinical studies with the company's lead drug candidate, Voreloxin, in the journal Cancer Chemotherapy and Pharmacology. The results demonstrate Voreloxin's potent cytotoxic activity in human acute leukemia cell lines and in an in vivo model when used alone, and enhanced or synergistic activity when used in combination with cytarabine.
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The company is currently completing Phase 2 studies of Voreloxin as a single-agent or in combination with cytarabine in acute myeloid leukemia (AML) and expects to begin Phase 3 testing in AML later in 2010.
Reportedly, Voreloxin, alone and in combination with cytarabine, was evaluated in 3 human acute leukemia cell lines: HL-60 (acute promyelocytic leukemia), MV4-11 (AML with a FLT3 mutation) and CCRF-CEM (acute lymphoblastic leukemia).
The result showed that Voreloxin was active in all the leukemia cell lines, including the AML cell line, which is relatively resistant to cytarabine in-vitro. Using a combination index (CI) analysis, Voreloxin with cytarabine demonstrated synergistic cytotoxic activity HL-60 and MV4-11 cells, and additive activity in CCRF-CEM cells.
In a series of elegant in vivo studies, a murine model of bone marrow ablation was used to evaluate the activity of Voreloxin and cytarabine alone and in combination. Bone marrow cellularity, peripheral white blood cell and platelet counts were monitored to assess the impact of and recovery from the study treatments.
The activity of Voreloxin at maximum tolerated dose (MTD) was superior to cytarabine at MTD. In addition, the combination demonstrated supra-additive activity in vivo, with a substantially enhanced, but fully reversible, reduction in bone marrow cellularity as compared to each agent alone.
Judith Fox, vice president of product and preclinical development at Sunesis,said: “These data contribute to our growing understanding of Voreloxin’s nonclinical profile, and, in keeping with our philosophy of clinical development informed by translational research, are directly relevant to our clinical program.
“We studied Voreloxin alone and in combination with cytarabine in leukemia cell lines, as well as in a mouse model of bone marrow ablation. The additive and synergistic effects of the combination in vitro, coupled with the supra-additive effects of the drugs in vivo, translate directly to our ongoing Phase 2 AML program. Importantly, the effects of Voreloxin and the combination regimen on bone marrow were fully reversible, mirroring the treatment paradigm for AML.”