Stuart Connolly 

Millions of people worldwide depend on Factor Xa inhibitors to manage the risk of blood clotting; however, the medication carries a risk of uncontrolled bleeding. For patients with acute intracranial hemorrhage (ICH) – life threatening brain bleeds – the need to counteract this risk is urgent, and has been under investigation for years at PHRI.

This week yielded some earlier-than-expected data that “we hope can pave the way for further guidance on the treatment of potentially life-threatening bleeds,” says PHRI Senior Scientist Stuart Connolly, prinicipal investigator of the phase IV, multicenter clinical trial, ANNEXa-I.

That trial has been halted for having met its pre-specified stopping criteria for superior hemostatic efficacy of the drug, andexanet alfa in patients with oral FXa- inhibitor associated ICH.

The recommendation to stop ANNEXa-I was made by the trial’s independent Data and Safety Monitoring Board following a planned interim assessment of efficacy, after 450 patients had been randomized and followed for one month – which showed the reversal benefits of ANDEXXA (Alexion AstraZeneca brand name of andexanaet alfa) on the oral FXa inhibitors apixaban and rivaroxaban.

Further data and analysis from ANNEXa-I to come; Connolly stated this week:

“We are pleased that the study has met its efficacy endpoint at the planned interim analysis, showing improved control of bleeding with targeted anticoagulation reversal, compared to usual care.
We look forward to sharing the full efficacy and safety results after further analysis – with the hope that the data will pave the way for further guidance on the treatment of potentially life-threatening bleeds.”

ANNEXa-I trial investigators, Europe, 2022

ANNEXa-I European investigators meeting in September 2022. PHRI investigators Stuart Connolly and Mike Sharma (standing) and Ashkan Shoamanesh (seated, far left).

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