Interim results from the REVERSE-IT trial of bentracimab (PhaseBio Pharmaceuticals), which is designed to study the reversal of the antiplatelet effects of ticagrelor in patients who present with a need for urgent surgery or an invasive procedure or who are experiencing uncontrolled major or life-threatening bleeding have been published in the New England Journal of Medicine (NEJM) Evidence.
The results of the prespecified interim analysis were previously presented on by Deepak L Bhatt (Brigham and Women’s Hospital and Harvard Medical School, Boston, USA) during a late-breaking science session at the American Heart Association’s Scientific Sessions 2021 (AHA 2021; 13–15 November; virtual).
The REVERSE-IT trial is expected to enrol approximately 200 major bleeding or urgent surgery patients at sites in the USA, Canada, the European Union and China.
Based on prior guidance from the US Food and Drug Administration (FDA), to balance the two patient populations, the REVERSE-IT trial does not allow enrolment of more than approximately two-thirds of either the uncontrolled major or life-threatening bleeding population or urgent surgery or invasive procedure population.
As the total number of patients enrolled in the prespecified interim analysis included 142 patients who required urgent surgery or an invasive procedure, PhaseBio has determined that the surgery cohort of the trial has been fully enrolled. With the successful completion of enrolment in this surgery cohort, REVERSE-IT trial sites have shifted focus to enrolling patients with uncontrolled major or life-threatening bleeding events. PhaseBio is seeking to accelerate enrolment of patients with uncontrolled major or life-threatening bleeding, including by working to increase the number of enrolling clinical trial sites as it believes that a broader site footprint will increase the probability of enrolling these patients.
Bentracimab has been studied in Phase 1 and Phase 2 clinical trials and demonstrated immediate and sustained reversal of the antiplatelet activity of ticagrelor, PhaseBio said in a press release. If these data are reproduced in the final results from the Phase 3 study, bentracimab may have the potential to bring life-saving therapeutic benefit to patients by potentially mitigating concerns regarding bleeding risks associated with the use of ticagrelor. Additionally, in a translational study, bentracimab achieved equivalent reversal of branded ticagrelor and multiple ticagrelor generics.
“We are pleased to see the publication of these highly positive interim Phase 3 results in a leading peer-reviewed scientific publication like NEJM Evidence,” said John Lee chief medical officer of PhaseBio. “This first analysis of bentracimab in patients demonstrated a remarkable safety profile with no drug-related serious adverse events reported and a low thrombotic event rate. Importantly, the highly significant clinical efficacy demonstrated in the surgical patients suggests strongly that we will see similar efficacy in bleeding patients upon completion of the study. Both urgent surgery and major, uncontrolled bleeding represent clear unmet needs for patients on ticagrelor worldwide who lack an effective reversal agent. We remain on track to submit our planned Biologics License Application (BLA) to the FDA in mid-2022 and intend to seek approval for both urgent surgery and major bleeding indications.”