August 14, 2019
PhaseBio Announces Receipt of Minutes of End-of-Phase 1 Meeting
PhaseBio Pharmaceuticals, Inc. (Nasdaq: PHAS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel therapies for orphan diseases, today announced the receipt of written minutes from the End-of-Phase 1 meeting with the U.S. Food and Drug Administration (“FDA”) that was held in July 2019.
The End-of-Phase 1 meeting was focused on gaining alignment with the FDA regarding the clinical and regulatory pathway for a potential U.S. approval of PB2452, a novel, recombinant, human monoclonal antibody antigen-binding fragment, or Fab, designed to reverse the antiplatelet activity of ticagrelor in major bleeding and urgent surgery situations.
Based on the written minutes from the End-of-Phase 1 meeting, PhaseBio believes that it has reached general agreement with the FDA on the overall design of a single, non-randomized, open label Phase 3 trial of major bleeding and urgent surgical populations to support the submission of a Biologics License Application (“BLA”) for potential accelerated approval of PB2452.
End-of-Phase 1 Meeting Details
During the End-of-Phase 1 meeting, the FDA generally agreed with the proposed clinical development plan and agreed that Accelerated Approval was the appropriate approval pathway for PB2452.
To further support safety assessments, the FDA recommended that PhaseBio include 200 active treatment subjects across its Phase 1 and Phase 2 trials, which includes the planned Phase 2b trial that will begin in the fourth quarter of 2019 and run in parallel to the ongoing Phase 2a and planned Phase 3 trial. To date, approximately 50 subjects have received PB2452 in the completed Phase 1 trial and ongoing Phase 2a trial. The Phase 2b trial is expected to enroll a total of 200 subjects, including 150 subjects who will be randomized to receive PB2452.
The FDA also recommended an assessment of PB2452 reversal in patients who may have supratherapeutic blood levels of ticagrelor as a result of ticagrelor overdosage or drug-drug interactions. Based on the pharmacokinetic and pharmacodynamic modeling conducted in earlier preclinical studies and clinical trials of PB2452, PhaseBio believes it has a clear understanding of the appropriate dosing regimen to reverse the antiplatelet effects of supratherapeutic blood levels of ticagrelor and plans to address this request in its ongoing Phase 2a trial, with dosing of these subjects to begin this quarter. PhaseBio expects to complete the Phase 2a trial in the fourth quarter of 2019.
With respect to the pivotal Phase 3 trial design, the FDA agreed with PhaseBio’s proposed 200 patient, non-randomized, open-label trial design and the proposed pharmacodynamic, clinical and safety endpoints. The FDA also agreed with the proposed use of the VerifyNow PRUTest®biomarker as the primary endpoint for the Phase 3 trial. PhaseBio has used VerifyNow PRUTest in its Phase 1 and Phase 2a clinical trials, where it demonstrated a high degree of correlation to other biomarkers used to measure platelet function. To support the BLA submission for Accelerated Approval, the FDA recommended that an interim analysis of the Phase 3 trial include data from the first 100 subjects treated with PB2452, with approximately 50 subjects from each of the major bleeding and surgical populations. To support full approval for patients with major bleeding or requiring urgent surgery, the FDA recommended enrollment of 200 total patients in the Phase 3 trial. PhaseBio expects to initiate the Phase 3 trial in the first quarter of 2020; based on an estimated 18-month enrollment timeline, a BLA could potentially be submitted in the second half of 2022. For post-approval commitments, the FDA recommended the completion of the remaining portions of the Phase 3 trial and the establishment of a post-approval registry.
“We are pleased with the constructive and collaborative discussion with FDA officials during the End-of-Phase 1 meeting,” said John Lee, M.D., Ph.D., Chief Medical Officer of PhaseBio. “We believe the specific next steps discussed at the meeting, and reflected in the minutes, represent a clear path toward BLA submission. The level of clarity and collaboration we received from the FDA is greatly appreciated. With PB2452 now having a defined development path, coupled with Breakthrough Therapy designation, we believe that we are well positioned to execute our strategy to deliver this potentially life-saving therapy to patients in need as soon as possible.”
[Originally posted by West — August 14, 2019]