US-based clinical-stage biopharmaceutical firm Sunesis Pharmaceuticals has started an investigator-sponsored Phase I/II trial of its lead product candidate vosaroxin, in adult patients with previously treated intermediate-2 or high-risk myelodysplastic syndrome (MDS).
The open-label, dose escalating Phase I/II study is being carried out at Weill Cornell Medical College and New York-Presbyterian Hospital under the guidance of Gail Roboz, associate professor of Medicine and director of the Leukemia Program.
Roboz said MDS remains a challenging disease in adult patients with few proven effective therapies.
"As a result, there is an urgent need for new treatments for MDS patients who have progressed after frontline treatment," Roboz said.
Forty patients with MDS who have previously failed treatment with hypomethylating agent-based therapy would be enrolled in the trial and initially a group of patients will be given escalating doses of vosaroxin over each 28 day treatment cycle.
After the maximum tolerated dose (MTD) is determined in the initial group, an expanded assessment of safety and haematologic response or improvement rate at the dose level will be carried out in additional subjects, so that the total number of subjects exposed to this dose level increases to about 15 subjects.
Apart from MTD and dose limiting toxicity, endpoints of the trial include rate of complete remission, partial remission, hematologic improvement and blood transfusion requirements.
Sunesis executive vice-president of development and chief medical officer Adam Craig said in the company’s early clinical work, single-agent vosaroxin has showed promising anti-leukemic activity and a favorable tolerability profile in elderly patients.
"Both elements provide a strong rationale for investigating its use as a treatment for MDS," Craig said. "We look forward to seeing the data collected by the team at Weill Cornell Medical College in this important area of unmet medical need, while we focus our internal resources on the completion of our fully-enrolled pivotal Phase 3 VALOR trial of vosaroxin in first relapsed or refractory AML patients."
Vosaroxin is an anti-cancer quinolone derivative (AQD), a class of compounds that has not been used previously for the treatment of cancer.
The company said the product both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis.
Vosaroxin has also got orphan drug designation from both the US Food and Drug Administration (FDA) and European Commission for the treatment of acute myeloid leukemia (AML).
In addition, the FDA has granted fast track designation to vosaroxin for the treatment of relapsed or refractory AML in combination with cytarabine.