Bentracimab (previously PB2452) has been studied in Phase 1 and Phase 2 clinical trials and has demonstrated the potential to bring life-saving therapeutic benefit through immediate and sustained reversal of the antiplatelet activity of ticagrelor, potentially mitigating concerns regarding bleeding risks associated with the use of antiplatelet drugs. Additionally, in a translational study, bentracimab achieved equivalent reversal of branded ticagrelor and multiple ticagrelor generics.
The pivotal Phase 3 clinical study is called REVERSE-IT (Rapid and SustainEd ReVERSal of TicagrElor – Intervention Trial). REVERSE-IT is a multi-center, open-label, prospective single-arm trial designed to study reversal of the antiplatelet effects of ticagrelor with bentracimab in patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or invasive procedure. Approximately 200 patients are being targeted to be enrolled from major health centers worldwide. Patients with reported use of ticagrelor within the prior 3 days who require urgent reversal due to uncontrolled major or life-threatening bleeding or because they need ticagrelor reversal will be eligible for enrollment.
As of March 2021, the REVERSE-IT Phase 3 clinical trial had enrolled 60 of the first approximately 100 patients needed to support a Biologics License Application (BLA), nearly all of whom to date have required urgent surgery or an invasive procedure. PhaseBio is attempting to accelerate enrollment of patients with uncontrolled major or life-threatening bleeding, including by working to increase the number of enrolling clinical trial sites in the United States, Canada, and the European Union as it is believed that a broader site footprint will increase the probability of enrolling these patients. The trial is enrolling faster than PhaseBio originally projected, and PhaseBio now expects to complete enrollment of the first 100 patients in mid-2021 and is targeting to submit a BLA for bentracimab in mid-2022, although those timelines could be impacted by the continued scope and duration of the COVID-19 pandemic.
We are also currently conducting a Phase 2B trial in older (ages 50-80) patients to evaluate the efficacy of bentracimab in reversal of ticagrelor. Enrollment is ongoing in the US and Canada with a 3:1 randomization (active: placebo). The primary endpoint is reversal measured by VerifyNow. The secondary endpoints are safety, PK and immunogenicity.
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