On June 13, 2016 Sunesis Pharmaceuticals (NASDAQ:SNSS) reported the presentation of updated results from an ongoing Phase 1b/2 University of Texas MD Anderson Cancer Center-sponsored trial of vosaroxin in combination with decitabine in older patients with previously untreated acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) (Press release, Sunesis, JUN 13, 2016, View Source;p=RssLanding&cat=news&id=2177015 [SID:1234513244]). The results were presented Saturday in an oral session titled "New Compounds in AML Treatment" at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark. The presentation (abstract S505, Bella Center, Hall A3), titled "Phase I/ll study of vosaroxin and decitabine in newly diagnosed older patients with acute myeloid leukemia and high-risk myelodysplastic syndrome," is available at www.sunesis.com.
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"Older patients diagnosed with AML and MDS have limited treatment options and exceedingly poor outcomes," said Naval Daver, M.D., Assistant Professor, Department of Leukemia, University of Texas MD Anderson Cancer Center, and a study investigator. "At the optimized induction dose of 70 mg/m2 of vosaroxin, the combination of vosaroxin and decitabine demonstrates a compelling CR/CRp/CRi rate of 76% and a median overall survival of 16.1 months. This response rate and survival are significantly better than seen with single-agent decitabine among similar patients at our institution. This outcome was achieved with <5% induction mortality and good tolerability. In this vosaroxin-decitabine cohort, 23 of 41 patients remain alive."
Daniel Swisher, CEO of Sunesis, added: "We believe these results warrant further exploration in a larger outcome study, with plans currently under review to conduct a multicenter clinical trial comparing vosaroxin plus decitabine and vosaroxin plus cytarabine to the 7+3 regimen in patients with AML."
To date, 63 patients (56 AML, 7 high-risk MDS) with a median age of 69 years (range 60-78) have been enrolled in the trial. All 63 patients have completed at least 2 treatment rounds, rendering them evaluable for response; with a 75% overall response rate, 49% (31 patients) achieved complete remission (CR), 17% (11 patients) achieved CR with incomplete platelet recovery (CRp), and 8% (5 patients) achieved CR with incomplete peripheral blood count recovery (CRi). The therapy was well-tolerated, with the main therapy related grade 3 or higher toxicities being mucositis in 11 (17%) patients.
Initially for the first 22 patients in the study, the selected induction dose of vosaroxin was 90 mg/m2. Thereafter to reduce the incidence of mucositis, the induction dose was reduced to 70 mg/m2 for the next 41 patients. The lower dose of vosaroxin in combination with decitabine was associated with reduced early mortality and an improved overall response rate and OS, as follows:
Induction
Dose
(vosaroxin) N Median
OS 8-week
Mortality Overall
Response Need >1 Cycle to
Response
90 mg/m2 22 5.5 27 % 73 % 19 %
70 mg/m2 41 16.1 5 % 76 % 42 %
Sunesis also announced that follow-up data from the company’s VALOR trial was presented as an e-poster during the EHA (Free EHA Whitepaper) meeting. The poster (abstract E930, Bella Center, E-Poster Screens), titled "Characterization of patients with relapsed or refractory AML in continued follow-up after treatment with vosaroxin/cytarabine vs placebo/cytarabine in the VALOR trial," shows that, as of January 22, 2016, 83 of 711 patients enrolled in VALOR remain alive (46/356 in the vosaroxin/cytarabine arm, 37/355 in the placebo/cytarabine arm) and in follow up, which has reached a median of 40 months. In patients ≥60 years, more than twice as many patients were alive in the vosaroxin/cytarabine arm (23 vs. 10 patients).
All but seven patients in this follow up underwent allogeneic hematopoietic stem cell transplant (HCT). Of note, the non-HCT survivors were all in the vosaroxin/cytarabine treatment arm (68-71 years old, 2 primary refractory and 5 early relapsed).
Mr. Swisher added: "We are encouraged by the long-term benefit seen in the VALOR follow-up and also the potential for vosaroxin and cytarabine to provide long-term benefit in older patients who need more options."
About QINPREZO (vosaroxin)
QINPREZO (vosaroxin) is an anti-cancer quinolone derivative (AQD), a class of compounds that has not been used previously for the treatment of cancer. Preclinical data demonstrate that vosaroxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Additionally, vosaroxin has been granted fast track designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction.
The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.