Vyxeos

Vyxeos is a liposomal formulation of a fixed combination of daunorubicin and cytarabine in a 1:5 molar ratio. The 1:5 molar ratio has been shown in vitro and in vivo to maximise synergistic antitumour activity in acute myeloid leukaemia (AML).

Daunorubicin has antimitotic and cytotoxic activity, which is achieved by forming complexes with deoxyribonucleic acid (DNA), inhibiting topoisomerase II activity, inhibiting DNA polymerase activity, affecting regulation of gene expression, and producing DNA-damaging free radicals.

Cytarabine is a cell cycle phase-specific antineoplastic agent, affecting cells only during the S phase of cell division. Intracellularly, cytarabine is converted into cytarabine-5-triphosphate (ara-CTP), which is the active metabolite. The mechanism of action is not completely understood, but it appears that ara-CTP acts primarily through inhibition of DNA synthesis. Incorporation into DNA and ribonucleic acid (RNA) may also contribute to cytarabine cytotoxicity. Cytarabine is cytotoxic to proliferating mammalian cells in culture.

Based on data in animals, Vyxeos liposomes accumulate and persist at a higher concentration in the bone marrow, where they are preferentially taken up intact by leukaemia cells. In leukaemia-bearing mice, the liposomes are taken up by leukaemia cells to a greater extent than by normal bone marrow cells. After internalisation, Vyxeos liposomes undergo degradation, releasing daunorubicin and cytarabine within the intracellular environment.