Xanthus Pharmaceuticals has begun patient dosing in a Phase III trial of its drug Xanafide. Patients with secondary acute myeloid leukemia are poorly served by existing drug therapy; physicians are therefore likely to be enthusiastic about a drug which can improve treatment outcomes. At this stage of development, however, it is too early to forecast the chances of Xanthus's drug being successful.
In the Phase III trial, secondary acute myeloid leukemia (sAML) patients will be randomized to receive either a combination of Xanafide (amonafide malate) and cytarabine or a combination of daunorubicin and cytarabine. Around 350 patients are expected to be enrolled in the trial. The primary endpoint will be rate of complete remission and secondary endpoints will include duration of remission and safety.
In 2007, acute myeloid leukemia (AML) is predicted to have an incidence of over 13,000 in the US and approximately 9,000 patients are expected to die from the disease. Driven partly by an aging population, the rate of incidence of AML is likely to increase significantly over the coming years. Secondary AML is AML which arises following myelodysplastic syndrome (MDS) or prior exposure to leukemogenic (leukemiainducing) therapy; the prognosis for these patients is particularly poor.
Data from a Phase II trial of Xanafide and cytarabine for the treatment of sAML were reported at the annual meeting of the American Society of Clinical Oncology in June 2007. A complete response was achieved in 44% of patients treated with this regimen. These findings were supplemented by preclinical data published in September 2007 which suggested that Xanafide may not lose its potency due to multi-drug resistance, unlike other cytotoxic therapies used to treat sAML.
The high level of unmet need which prevails in sAML could potentially drive significant uptake of a drug or drug regimen which can improve treatment outcomes in this disease. Currently available combinations of cytotoxic therapies (such as daunorubicin and cytarabine) are associated with complete response rates of around 40-50% and when a response occurs, the duration of remission is typically short. Consequently, while such regimens represent the current mainstay of AML treatment, they are not considered standard of care in sAML.
It is difficult to say, based on the Phase II trial data, whether Xanafide is likely to demonstrate sufficient improvement over existing cytotoxic regimens to be considered as a viable treatment option for sAML patients. Xanthus will no doubt hope that the lack of multi-drug resistance indicated in preclinical trials will translate into a real clinical advantage in the ongoing trial.