28 January 2021 - - US-based biopharmaceutical company PhaseBio Pharmaceuticals, Inc. (NASDAQ: PHAS), in conjunction with its financing and co-development partner for the European Union and China, SFJ Pharmaceuticals, PhaseBio, has expanded its pivotal Phase 3 REVERSE-IT trial for its lead product candidate bentracimab into the European Union, having opened trial sites for enrollment and begun dosing its first patients, the company said.

Bentracimab is a novel, human monoclonal antibody fragment that in earlier clinical trials has shown immediate and sustained reversal of the antiplatelet effects of Brilinta (ticagrelor).

Bentracimab 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 this antiplatelet drug. Additionally, in a translational study, bentracimab achieved equivalent reversal of branded ticagrelor and multiple ticagrelor generics.

Estimates from IQVIA for 2019 suggest nearly 450,000 patients on Brilinta (ticagrelor) in the United States, and approximately 1.2m patients on Brilinta/Brilique (ticagrelor) in the 27 countries comprising the European Union, plus the United Kingdom, Switzerland, and Norway.

REVERSE-IT (Rapid and SustainEd ReVERSal of TicagrElor Intervention Trial) 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 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 ticagrelor reversal will be eligible for enrollment.

Bentracimab is a novel, recombinant, human monoclonal antibody antigen-binding fragment designed to reverse the antiplatelet activity of ticagrelor in major bleeding and urgent surgery situations.

In a Phase 1 clinical trial, bentracimab demonstrated the potential to bring life-saving therapeutic benefit through immediate and sustained reversal of ticagrelor's antiplatelet activity, mitigating concerns regarding bleeding risks associated with the use of this antiplatelet drug.

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 Food and Drug Administration. Breakthrough Therapy Designation may be granted by the FDA when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapy.

In September 2019, PhaseBio completed a Phase 2a trial in which bentracimab was investigated in older and elderly subjects on dual antiplatelet therapy of ticagrelor and low-dose aspirin.

Additionally, the Phase 2a trial investigated a bentracimab regimen for the reversal of supratherapeutic doses of ticagrelor in healthy younger subjects.

In both arms of the trial, bentracimab achieved immediate and sustained reversal of the antiplatelet effects of ticagrelor and was generally well-tolerated, with only minor adverse events reported.

These results are consistent with the results observed in healthy younger subjects treated with ticagrelor in the previously published Phase 1 trial.

PhaseBio initiated the REVERSE-IT trial, a pivotal Phase 3 clinical trial of bentracimab, in March 2020 to support a Biologics License Application for bentracimab in both major bleeding and urgent surgery indications.

There are currently no approved reversal agents for ticagrelor or any other antiplatelet drugs.

PhaseBio Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for cardiovascular and cardiopulmonary diseases.

The company's pipeline includes: bentracimab (PB2452), a novel reversal agent for the antiplatelet therapy ticagrelor; pemziviptadil (PB1046), a once-weekly vasoactive intestinal peptide receptor agonist for the treatment of pulmonary arterial hypertension; and PB6440, an oral agent for the treatment of resistant hypertension.

PhaseBio's proprietary elastin-like polypeptide technology platform enables the development of therapies with potential for less-frequent dosing and improved pharmacokinetics, including pemziviptadil, and drives both internal and partnership drug-development opportunities.