Investigators have presented full results from a late-stage study which sheds more light on Sanofi’s decision to halt development of its injectable factor Xa inhibitor otamixaban.
Data from the TAO study, presented at the European Society of Cardiology congress in Amsterdam, show that otamixaban significantly increased bleeding without reducing mortality or new heart attacks compared to currently recommended therapy among patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) who were scheduled for an early invasive strategy.
The study failed to meet its primary endpoint showing superiority of otamixaban over a combination of unfractionated heparin and eptifibatide in moderate- to high-risk NSTE-ACS patients scheduled to undergo angiography and potentially percutaneous coronary intervention within three days of randomisation.
“The risk of major or minor bleeding was approximately doubled with otamixaban across all patient subgroups, and a lower dose did not achieve better results,” said the study’s lead investigator Philippe Steg of the Hôpital Bichat in Paris. He added that the results “suggest an unfavourable efficacy/safety balance for acute injectable Xa inhibition in the setting of ACS treated with modern antiplatelet therapy and routine early intervention”.
Sanofi discontinued development of otamixaban in June.
Also at ESC, Boehringer Ingelheim presented data from the discontinued RE-ALIGN trial which was looking at the firm’s anticoagulant Pradaxa (dabigatran) in patients with mechanical prosthetic heart valves
Treatment with Pradaxa increased thromboembolic and bleeding events compared to warfarin in patients with mechanical heart valve replacements. Following an interim analysis, the trial was discontinued last year and in December 2012 the European Medicines Agency and the US Food and Drug Administration issued a contraindication for the drug in this patient population.
“The RE-ALIGN trial results do not support the use of dabigatran in patients with mechanical heart valves,” lead investigator Frans Van de Werf of the University of Leuven, Belgium, told an ESC press briefing. He believes that warfarin is more effective in the setting of mechanical valves because it also inhibits synthesis of factor IX of the contact pathway while dabigatran exclusively inhibits thrombin.
If correct, this would mean that factor Xa inhibitors such as Bayer/Johnson & Johnson’s Xarelto (rivaroxaban) and Pfizer/Bristol-Myers Squibb’s Eliquis (apixaban) work for this indication either, he added.
In a press release, Boehringer Ingelheim said Pradaxa remains widely approved in other cardiovascular/VTE indications and that extensive in-market experience of over two million patient-years in all licensed indications “puts Pradaxa first among the novel oral anticoagulants.”
