MALVERN, PA & SAN DIEGO–(BUSINESS WIRE)–PhaseBio Pharmaceuticals, Inc. (Nasdaq: PHAS), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies for cardiopulmonary diseases, today announced the release of interim results from REVERSE-IT (Rapid and SustainEd ReTOWARDal of TicagrEgold- Inintervention Jrial) in the New England Journal of Medicine Evidence, a new digital journal from the New England Journal of Medicine (NEJM) group. REVERSE-IT is PhaseBio’s ongoing pivotal Phase 3 trial of its lead product, bentracimab, which is designed to study the reversal of the antiplatelet effects of ticagrelor in patients with either (i) a need for urgent surgery or an invasive procedure or (ii) who experience major uncontrolled or life-threatening bleeding.
The results of the predefined interim analysis were previously presented on November 15, 2021 by Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital and professor at Harvard Medical School, during a Late -Breaking Science Session at the 2021 American Heart Association Scientific Sessions.
“We are delighted to see the publication of these very positive Phase 3 interim results in a leading peer-reviewed scientific publication such as NEJM Evidence,” said John Lee, MD, Ph.D., Chief Medical Officer of PhaseBio . “This first analysis of bentracimab in patients demonstrated a remarkable safety profile with no reported serious drug-related adverse events and a low rate of thrombotic events. Importantly, the highly significant clinical efficacy demonstrated in surgical patients strongly suggests that we will see similar efficacy in bleeding patients at the end of the study. Urgent surgery and major uncontrolled bleeding represent clear unmet needs for patients on ticagrelor worldwide who do not have an effective reversal agent. We remain on track to submit our planned Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in mid-2022 and intend to seek approval both for urgent surgeries and major bleeding indications.
REVERSE-IT clinical program
The REVERSE-IT trial is expected to enroll approximately 200 patients with major bleeding or emergency surgery at sites in the United States, Canada, European Union and China. Based on FDA advance guidelines, to balance the two patient populations, the REVERSE-IT trial does not allow enrollment of more than approximately two-thirds of the uncontrolled major or life-threatening bleeding population or the emergency surgery or invasive procedure population. Because the total number of patients enrolled in the pre-specified interim analysis included 142 patients requiring urgent surgery or an invasive procedure, PhaseBio determined that the trial’s surgical cohort was fully recruited. With the successful completion of enrollment in this surgical cohort, the REVERSE-IT trial sites have focused on enrolling patients with uncontrolled major or life-threatening bleeding events. PhaseBio seeks to accelerate the recruitment of patients with major or life-threatening uncontrolled bleeding, including working to increase the number of recruiting clinical trial sites, as it believes that a larger site footprint will increase the probability of recruiting these patients.
The FDA has 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 expedited approval of bentracimab. The FDA recommended that the 100 patients in the interim analysis include approximately 50 patients from each of the major or life-threatening bleeding populations and the emergency surgery or invasive procedure population, although the FDA noted that there is a sufficient number of patients from either cohort. would be a matter of review and considered in the context of other data submitted with the BLA. PhaseBio begins the preparation of the BLA and aims for a BLA submission to the FDA in mid-2022.
Bentracimab has been studied in Phase 1 and Phase 2 clinical trials and has demonstrated immediate and long-lasting reversal of the antiplatelet activity of ticagrelor. If these data are replicated in the final Phase 3 study results, bentracimab could potentially provide life-saving therapeutic benefit to patients by potentially alleviating concerns about bleeding risks associated with the use of ticagrelor. Additionally, in a translational study, bentracimab achieved an equivalent reversal of brand name ticagrelor and several generic ticagrelor.
About bentracimab (PB2452)
Bentracimab is a novel recombinant human monoclonal antibody antigen-binding fragment designed to reverse the antiplatelet activity of ticagrelor in major bleeding and emergency surgery situations. In a Phase 1 clinical trial, bentracimab demonstrated the potential to provide life-saving therapeutic benefit through immediate and sustained reversal of the antiplatelet activity of ticagrelor, alleviating concerns about bleeding risks associated with use of this antiplatelet drug. Data from the Phase 1 clinical trial of bentracimab in healthy volunteers was published in the New England Journal of Medicine in March 2019. In April 2019, bentracimab received Breakthrough Therapy Designation from the FDA. In September 2019, PhaseBio completed a Phase 2a trial in which bentracimab was studied in healthy, elderly, elderly subjects on dual antiplatelet therapy of ticagrelor and low-dose aspirin. Additionally, the phase 2a trial investigated a bentracimab regimen for reversal of supratherapeutic doses of ticagrelor in young healthy subjects. In November 2021, PhaseBio completed a Phase 2b trial in which bentracimab was studied in healthy, elderly, elderly subjects on dual antiplatelet therapy of ticagrelor and low-dose aspirin. In all active treatment arms of the Phase 2a and Phase 2b trials, bentracimab achieved immediate and durable reversal of the antiplatelet effects of ticagrelor and was generally well tolerated, with only minor adverse effects reported. These results are consistent with the results observed in younger healthy subjects treated with ticagrelor in the previously published phase 1 trial. PhaseBio initiated REVERSE-IT, a pivotal Phase 3 clinical trial of bentracimab, in March 2020 to support a potential biologics license application for bentracimab in the major bleeding and emergency surgery indications.
PhaseBio Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for cardiovascular and cardiopulmonary diseases. PhaseBio’s pipeline includes: bentracimab (PB2452), a novel antiplatelet therapy reversal agent ticagrelor; pemziviptadil (PB1046), a once-weekly vasoactive intestinal peptide (VIP) receptor agonist for the treatment of pulmonary arterial hypertension; and PB6440, an oral agent for the treatment of resistant hypertension. PhaseBio’s patented elastin-like polypeptide technology platform enables the development of therapies with less frequent dosing potential and improved pharmacokinetics, including pemziviptadil, and generates in-house drug development and partnership opportunities.
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Forward-looking statements include statements regarding or involving the conduct or timing of our clinical trials and our research, development and regulatory plans for our product candidates, the timing of availability or disclosure of data from such clinical trials and the timing of expected regulatory submissions, the possibility that such product candidates will receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, such product candidates will be successfully distributed, marketed and marketed. Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements are not guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements.
Risks relating to our business are described in detail in our filings with the Securities and Exchange Commission, including our Quarterly Report on Form 10-Q for the quarter ended September 30, 2021. These forward-looking statements speak only as of the date hereof, and PhaseBio Pharmaceuticals, Inc. disclaims any obligation to update these statements except as required by law.