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Celator(R) Pharmaceuticals Presents Data on the Activity of CPX-351 Against Leukemia at the European Hematology Association Congress
Date:6/8/2009

current analysis confirmed that CPX-351 maintained the fixed 5:1 molar ratio of cytarabine:daunorubicin for prolonged periods of time (24 hours and longer) after administration. It also showed that while the bioavailability of the encapsulated drugs was similar to that expected with conventional administration, CPX-351 produced prolonged half-lives for both agents and accumulation of the drugs over the three dose induction course (infusions on Days 1, 3, 5). These results suggest that effective drug exposure could be extended beyond that produced by conventional administration of this drug combination. The further observation that circulating liposomal drug could be detected in the plasma up to Day 12, while remaining bioavailable, led the investigators to conclude that leukemia cells could be exposed to cytotoxic drug levels throughout the first two weeks of induction treatment.

In a separate poster presentation, researchers described the results of a preclinical study comparing the sensitivity of various blood cell types to CPX-351 and evaluating the uptake of CPX-351 by human leukemia cells both in vitro and in vivo (mouse xenograft models).(2) They reported that CPX-351 ablated leukemic cells but permitted the regrowth of normal bone marrow cells within 42 days of treatment in a Rag2-M mouse xenograft model. These mice remained leukemia-free for up to 70 days (saline-treated controls all died by Day 42). In several additional experiments, investigators confirmed the presence of intact CPX-351 liposomes inside the leukemia cells, allowing the release of the synergistic 5:1 molar ratio of the active agents intracellularly, and demonstrated that CPX-351 is taken up in higher levels by leukemic cells in the bone marrow than by normal bone marrow cells. They concluded that the preferential uptake of CPX-351 by leukemia cells may contribute to its enhanced efficacy and improved therapeutic index.

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