PhaseBio's PB2452 (Bentracimab) Receives CDE Breakthrough Therapy Designation for Reversal of Ticagrelor’s Antiplatelet Effects

On December 15, the CDE website showed that PB2452 Injection (bentracimab) is proposed to be included in the breakthrough therapy category. The indication is for adult patients with uncontrolled major bleeding or life-threatening bleeding after receiving ticagrelor treatment, or those requiring reversal of ticagrelor’s antiplatelet effects before emergency surgery or intervention.

Ticagrelor, developed by AstraZeneca, is a reversible, direct-acting oral P2Y12 receptor antagonist used for the prevention and treatment of thrombotic events in patients with acute coronary syndrome (ACS) and cardiovascular and cerebrovascular diseases. It has antiplatelet effects but also carries the risk of bleeding. PB2452, developed by PhaseBio, is a neutralizing monoclonal antibody fragment that binds with high affinity to ticagrelor and its active metabolites, reversing the antiplatelet effects of ticagrelor.

In April 2019, PB2452 received Breakthrough Therapy Designation from the U.S. FDA for reversing the antiplatelet effects of ticagrelor. This designation was based on Phase I clinical data published in The New England Journal of Medicine. The results showed that PB2452 could immediately and continuously reverse the antiplatelet effects of ticagrelor.

Recently, at the 2021 American Heart Association (AHA) Scientific Sessions, PhaseBio announced the pre-specified interim analysis results of the Phase III clinical trial (REVERSE-IT) for PB2452.

REVERSE-IT is an international, multicenter, open-label, single-group Phase III clinical trial designed to investigate the reversal effect of PB2452 on ticagrelor’s antiplatelet activity in patients with uncontrolled, massive or life-threatening bleeding, or those requiring urgent surgery or invasive procedures. The study aims to support its Biologics License Application (BLA) for major bleeding and urgent surgery indications. A total of 150 patients who were taking ticagrelor and received Bentracimab injections were enrolled in the study, including 142 patients who underwent planned urgent surgery (92% cardiac surgery) and 8 patients with uncontrolled or life-threatening major bleeding.

The results showed that PB2452 could immediately and continuously reverse the antiplatelet effect of ticagrelor in patients requiring emergency surgery and severe bleeding, reaching the primary endpoint. Within 5-10 minutes after PB2452 administration, platelet inhibition decreased by 135% (p<0.01) and lasted for over 24 hours. In the vast majority of cases, the drug's hemostatic efficacy was rated as good or excellent, with no drug-related serious adverse events or allergic reactions observed. PhaseBio plans to submit a marketing application to the FDA by mid-2022.