Date: 2016-08-25
Type of information: Publication of results in a medical journal
phase:
Announcement: publication of results in Drugs
Company: Sunesis Pharmaceuticals (USA - CA)
Product: Qinprezo™ (vosaroxin)
Action
mechanism: antibiotic/quinolone/topoisomerase II inhibitor. Qinprezo™ (vosaroxin) is an anti-cancer quinolone derivative, 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 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.
Disease: acute myeloid leukemia
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On August 25, 2016, Sunesis Pharmaceuticals, announced the publication of an article detailing the molecular and pharmacologic properties of vosaroxin as a new therapeutic for acute myeloid leukemia (AML) in the journal Drugs. The article is titled "Molecular and Pharmacologic Properties of the Anticancer Quinolone Derivative Vosaroxin: A New Therapeutic for Acute Myeloid Leukemia," and will appear in the September 2016 print issue of Drugs. A MAA Marketing Authorization Application for vosaroxin as a treatment for AML in Europe is currently under review by the European Medicines Agency .
The authors describe how the unique chemical and pharmacologic characteristics of vosaroxin, the first quinolone-based topoisomerase II inhibitor studied in clinical trials in cancer, may contribute to the efficacy and safety profile observed in Sunesis' Phase 3 VALOR trial, a randomized, double-blind, placebo-controlled trial of vosaroxin and cytarabine in patients with first relapsed or refractory AML. Vosaroxin is a DNA intercalating topoisomerase II inhibitor that causes the induction of apoptosis via double-strand DNA breaks, yet is chemically distinct from other topoisomerase inhibitors with its stable quinolone-based core. Due to the stability of this core, vosaroxin is not associated with significant formation of toxic metabolites, free radicals, or reactive oxygen species, which are associated with off-target organ damage and cardiotoxicity. Furthermore, vosaroxin evades two common mechanisms of drug resistance, as it is not a substrate for the P-glycoprotein efflux pump and its activity is maintained in cells with p53 deletion.
In the pivotal Phase 3 VALOR trial, a 2.1-month improvement in median OS among patients = 60 years old was demonstrated, without an increase in early mortality, as compared to the control arm. Common side effects of vosaroxin included gastrointestinal effects, myelosuppression, and infection. Vosaroxin also demonstrates potent in vitro antitumor activity in various tumor types, including those resistant to other topoisomerase II inhibitors.
Vosaroxin is currently being tested in several investigator-sponsored studies, both as a single-agent and in combination with other therapies, for the treatment of AML and myelodysplastic syndromes.
