On October 6, 2014 Sunesis Pharmaceuticals reported the results from the pivotal Phase 3 VALOR trial (NCT01191801), a randomized, double-blind, placebo-controlled trial of vosaroxin and cytarabine in patients with first relapsed or refractory acute myeloid leukemia (AML) (Press release Sunesis, OCT 6, 2014, View Source [SID:1234500789]). At more than 100 leading international sites, the trial enrolled 711 patients, who were stratified for age, geography and disease status. The trial did not meet its primary endpoint of demonstrating a statistically significant improvement in overall survival, with a median overall survival of 7.5 months for vosaroxin and cytarabine compared to 6.1 months for placebo and cytarabine (HR=0.865, p=0.06). Because transplant may confound the primary analysis, a predefined analysis of overall survival censoring for stem cell transplantation was planned. In this analysis, patients receiving the vosaroxin combination had a median overall survival of 6.7 months versus 5.3 months for placebo and cytarabine (HR=0.809, p=0.02). The trial also demonstrated a clinically significant benefit in complete remission (CR) rate (30.1% vs 16.3%, p=0.0000148), the secondary endpoint.

For age, the trial stratified patient populations into age 60 years and older and younger than 60 years at enrollment. Within a predefined analysis of patients younger than 60 years (n=260), where the rate of stem cell transplant was 45.8%, the vosaroxin combination demonstrated a median overall survival of 9.1 months, versus 7.9 months for placebo and cytarabine (HR=1.079, p=NS), and a CR rate of 26.9% versus 20.8% (p=0.24). In the analysis of patients aged 60 years and older (n=451), where the rate of stem cell transplant was 20.2%, the vosaroxin combination demonstrated a median overall survival of 7.1 months, versus 5.0 months for placebo and cytarabine (HR=0.755, p=0.006), and a CR rate of 31.9% versus 13.8% (p=0.0000048).

In the intent-to-treat population, Grade 3 or higher non-hematologic adverse events that were more common in the vosaroxin combination arm were gastrointestinal and infection-related toxicities, consistent with those observed in previous company trials. The rate of serious adverse events was 55.5% in the vosaroxin combination arm compared to 35.7% in the placebo and cytarabine arm. Thirty-day and 60-day all-cause mortality were comparable between the trial arms (7.9% versus 6.6% and 19.7% versus 19.4%, for the vosaroxin combination versus placebo and cytarabine, respectively).

Based on results of the trial, Sunesis plans to commence a marketing authorization application with the European Medicines Agency (EMA) and to meet with the U.S. Food and Drug Administration to determine the appropriate regulatory path forward.

The results reported above are based upon Sunesis’ analysis of the data to date. Detailed results of the VALOR trial will be submitted for presentation at an upcoming medical conference.

“VALOR was a robust, well-conducted trial, among the largest in the relapsed or refractory AML setting. The study outcomes are very encouraging, and I look forward to a full presentation of the data in a peer-reviewed forum,” said Robert Stuart, M.D., Professor of Medicine, Division of Hematology/Oncology, Department of Medicine, Medical University of South Carolina, an investigator in the VALOR study and chairman of the study’s steering committee. “The clinical benefit is particularly impressive in patients aged 60 years and older, a population for whom there is no therapeutic standard of care.”

“There remains an acute need for new treatment options in AML, particularly relapsed refractory patients, where no therapy has demonstrated a survival benefit in a pivotal Phase 3 trial in more than 40 years,” said Adam Craig, M.D., Ph.D., Executive Vice President, Development and Chief Medical Officer of Sunesis. “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.”

“We are deeply grateful for the support and commitment of the AML investigators, the patients and families who took part in or contributed to VALOR,” said Daniel Swisher, Chief Executive Officer of Sunesis. “We look forward to presenting these data in detail to regulators in both Europe and the U.S. and to reporting on our progress and plans as they develop.”