A phase III trial of vosaroxin failed to meet its primary overall survival endpoint in patients with first relapsed or refractory acute myeloid leukemia.
A phase III trial of vosaroxin, a quinolone derivative of a class not previously used in cancer therapy, failed to meet its primary endpoint in patients with first relapsed or refractory acute myeloid leukemia (AML). The study did show promise with certain secondary endpoints, but overall survival was no better with vosaroxin (Qinprezo) and cytarabine than with placebo and cytarabine. The subgroup benefits, though, may lead the company to seek approval of the drug.
“There remains an acute need for new treatment options in AML, particularly relapsed or refractory patients, where no therapy has demonstrated a survival benefit in pivotal phase III trial in more than 40 years,” said Adam Craig, MD, PhD, the chief medical officer of Sunesis Pharmaceuticals, which develops vosaroxin, in a press release.
The VALOR trial included 711 patients at more than 100 international sites. The median overall survival for the vosaroxin group was 7.5 months, compared with 6.1 months for the placebo group, for a hazard ratio (HR) of 0.865 (P = .06). In a predefined analysis censoring for stem cell transplantation, the median overall survival was 6.7 months for vosaroxin and 5.3 months for placebo, which did reach significance with an HR of 0.809 (P = .02).
The secondary endpoint, complete remission rate, was significantly better as well with vosaroxin, at 30.1% vs 16.3% (P < .0001). Among a subgroup of 451 patients aged 60 years and older, the median overall survival with vosaroxin was 7.1 months compared with 5 months for placebo patients, for an HR of 0.755 (P = .006). In that older cohort, the complete remission rate was 31.9% with vosaroxin and 13.8% with placebo.
Earlier research on vosaroxin showed that the agent intercalates DNA and inhibits topoisomerase II, resulting in site-selective DNA damage. The US Food and Drug Administration (FDA) and the European Commission have granted vosaroxin orphan drug designation, and the FDA has granted it fast track designation, allowing for more rapid movement through approvals process.
“While we continue to evaluate the findings of VALOR in their totality, we believe the results demonstrate a clinically meaningful and important advancement in the treatment of this disease,” Craig said. The company plans to submit a marketing authorization application to the European Medicines Agency on the strength of this analysis, and will meet with the FDA to determine a path forward in the United States.