PhaseBio Pharmaceuticals, Inc. announced that it has enrolled the first 143 patients in its pivotal phase 3 REVERSE-IT trial for its lead product candidate bentracimab, 138 of whom required urgent surgery or an invasive procedure and five of whom experienced uncontrolled major or life-threatening bleeding. The company is commencing preparation of the BLA and targeting a BLA submission to the U.S. Food and Drug Administration (FDA) in mid-2022. The REVERSE-IT trial is expected to enroll approximately 200 major bleeding or urgent surgery patients at sites in the United States, Canada, the European Union and China. Based on prior guidance following the end of phase 1 meeting with the FDA to balance the two patient populations, the REVERSE-IT trial does not allow enrollment of more than approximately two thirds of either the uncontrolled major or life-threatening bleeding population or urgent surgery or invasive procedure population. Because the total number of patients enrolled to date includes 138 patients who required urgent surgery or an invasive procedure, the surgery cohort of the trial has been fully enrolled. With the successful completion of enrollment in this surgery cohort, REVERSE-IT trial sites have shifted focus to enrolling patients with uncontrolled major or life-threatening bleeding events. The company is continuing to attempt 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 believes that a broader site footprint will increase the probability of enrolling these patients. Additionally, the company expects to begin enrolling the first patients at sites in China later in 2021. The FDA also previously indicated that an interim analysis of the first approximately 100 patients enrolled in the REVERSE-IT trial would be sufficient to support the submission of a BLA for accelerated approval. The FDA recommended that the 100 patients comprising the interim analysis include approximately 50 patients from each of the uncontrolled major or life-threatening bleeding population and the urgent surgery or invasive procedure population, although the FDA noted that whether there are an adequate number of patients from either cohort would be a review issue and considered in the context of other data submitted with the BLA. All of the patients enrolled in the REVERSE-IT trial, both in the urgent surgery and major bleeding cohorts as described above, will be measured against the same VerifyNow® PRUTest biomarker, which is the primary endpoint for the interim analysis and a co-primary endpoint for the full trial. Hemostasis is the other co-primary endpoint for the REVERSE-IT trial. Following a 35-day safety follow-up period from the date of last patient enrollment, the company will lock the trial database and analyze the data, with the expectation of providing top-line safety and efficacy results from the interim analysis later this year. Full results from the interim analysis are planned to be presented at an upcoming medical congress and published. In conjunction with the updates regarding the phase 3 REVERSE-IT trial, the company also announced now the completion of enrollment in the randomized, double-blind, placebo-controlled phase 2b trial of bentracimab. The phase 2b trial enrolled 200 healthy older and elderly (ages 50 to 80) subjects on dual antiplatelet therapy of ticagrelor and low-dose aspirin; 150 subjects were randomized to receive bentracimab, with reversal of the antiplatelet effects of ticagrelor, as measured by the VerifyNow® PRUTest biomarker, serving as the primary endpoint for the trial. Top-line results from the phase 2b trial are expected later this year. The phase 2b trial was designed to supplement the safety and efficacy results that will be included in the planned BLA submission. Bentracimab is currently in late-stage clinical development in the REVERSE-IT (Rapid and SustainEd ReVERSal of TicagrElor – Intervention Trial) trial. REVERSE-IT is a phase 3, 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 an invasive procedure.