September 1, 2009 – Sanofi-aventis said Sunday the investigational anti-Xa intravenous anti-coagulant otamixaban reduced by 27 to 42 percent 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 today at the plenary session of the annual European Society of Cardiology Congress in Barcelona and simultaneously published online in The Lancet.
Otamixaban is a first in class, rapid onset anti-thrombotic compound, acting as a direct selective inhibitor of factor Xa. Otamixaban originated from sanofi-aventis thrombosis research portfolio and is currently in phase IIb clinical development phase.
“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 Dr. Marc Sabatine, M.D., MPH, an investigator in the TIMI Study Group and a cardiologist at Brigham and Women’s Hospital, Harvard Medical School. “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.”
The double-blind phase II SEPIA-ACS1/TIMI-42 study randomized 3241 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. The SEPIA-ACS1 study 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 anti-thrombotic 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. The company said a combined analysis of the intermediate doses (0.105 and 0.140 mg/kg/h) of otamixaban arms showed otamixaban reduced by about 46 percent the risk of the composite of death or a second myocardial infarction, a predefined study secondary efficacy endpoint.
The potent anti-thrombotic effect of otamixaban was also accompanied with a dose-dependent bleeding profile. Combined intermediate otamixaban dosages showed a safety profile not statistically different with regard to TIMI major or minor bleeding through seven days, in comparison to UFH and GPIIb/IIIa inhibitor comparator.
Acute coronary syndromes is a general term used to regroup clinical symptoms related to acute
myocardial ischemia. ACS represents an area of important medical need, as despite use of several anti-thrombotic therapies, death and myocardial infarction still occur in 5 to 8 percent of patients in the following week after an initial event.
For more information: www.sanofi-aventis.com