Sanofi-Aventis' otamixaban substantially reduced complications of invasive management of acute coronary syndromes

French drug major Sanofi-Aventis says that its investigational anti-Xa intravenous anticoagulant otamixaban reduced by 27% to 42% the odds of the composite primary endpoint of death, myocardial infarction, urgent revascularization or rescue GPIIb/IIIa use in four out of the five otamixaban tested doses, versus standard UFH/eptifibatide combination in [non-ST] ACS patients suitable for invasive strategy. The results of the SEPIA-ACS1/ TIMI-42 were presented at the plenary session of the annual European Society of Cardiology congress in Barcelona, Spain, and simultaneously published on-line in The Lancet.

Otamixaban is a first in class, rapid onset antithrombotic compound, acting as a direct selective inhibitor of factor Xa.

"The data show that intermediate dosages of otamixaban may offer substantial reduction in major coronary complications in patients presenting with acute coronary syndrome, with bleeding rate comparable to current therapy," said Marc Sabatine, an Investigator in the TIMI Study Group and a cardiologist at Brigham and Women's Hospital, Harvard Medical School, USA. "This research is addressing an important medical need, by potentially significantly improving outcomes of ACS patients undergoing PCI while simplifying the treatment pattern of the acute management phase of the disease," he added.

The double-blind Phase II SEPIA-ACS1/ TIMI-42 study randomized 32,41 patients from 36 countries in six treatment arms. The study assessed the efficacy and safety of five different doses of otamixaban versus the standard unfractionated heparin plus Glycoprotein IIb/IIIa inhibitor (eptifibatide), on background of standard dual antiplatelet therapy, in patients with high-risk non-ST-elevation acute coronary syndromes.

SEPIA-ACS1 showed that otamixaban displayed clinically meaningful activity on the primary endpoint from the threshold dose of 0.070 mg/kg/h, the second tested dose, with a consistent antithrombotic effect up to the fifth highest tested dosage. The lowest studied dosage was prematurely stopped due to insufficient activity, based on recommendation by an independent data monitoring board. Moreover a combined analysis of the intermediate doses (0.105 and 0.140 mg/kg/h) of otamixaban arms showed that otamixaban reduced by approximately 46% (p=0.0198) the risk of the composite of death or a second myocardial infarction, a predefined study secondary efficacy endpoint.