Presentation Details
| Safety and Efficacy of the Anti-Tissue Factor Pathway Inhibitor Marstacimab in Participants With Severe Hemophilia Without Inhibitors: Results From the Phase 3 Basis Trial and Ongoing Long-Term Extension Study Suchitra S.Acharya1, Davide Matino2, Andrew Palladino3, Eunhee Hwang3, Regina McDonald4, Carrie Turich Taylor5, John Teeter5. 1Cohen Children's Medical Center, Northwell Hemostasis and Thrombosis Center, Northwell Health, New Hyde Park, NY, USA.2McMaster University, 237 Barton St.East, Hamilton, ON, Canada.3Pfizer Inc, Collegeville, PA, USA.4Pfizer Inc, New York, NY, USA.5Pfizer Inc, Groton, CT, USA |
Abstract
Background: Marstacimab (PF-06741086) is a monoclonal antibody targeted to the tissue factor pathway inhibitor protein to improve hemostasis via the extrinsic coagulation pathway. BASIS (NCT03938792) is an open-label, pivotal phase 3 study of marstacimab in participants with severe (factor [F]VIII ˂1%) hemophilia A (HA) or moderately severe to severe (FIX ≤2%) hemophilia B (HB), with or without inhibitors. Objective: To evaluate the safety and efficacy of marstacimab in participants without inhibitors compared with previous factor replacement therapy. Methods: Screened males aged ≥12-<75 years with severe HA or moderately severe to severe HB entered a 6-month observational phase (OP) and received on demand (OD) or routine prophylaxis (RP) therapy. Participants then entered a 12-month active treatment phase (ATP) and received a single loading dose of 300 mg subcutaneous marstacimab followed by 150 mg once/week. Primary endpoints were annualized bleeding rate (ABR) for treated bleeds and safety outcomes. Secondary endpoints included ABR of bleed categories. Participants could enroll in the long-term extension (LTE) study (NCT05145127). Results: In total, 128 participants (median age, 30 [range 13-66] years) entered the OP (OD: HA n=29, HB n=8; RP: HA n=72, HB n=19), 116 (OD, n=33; RP, n=83) were dosed in the ATP, and 107 continued in the LTE (data cut: OD, n=32; RP, n=75; duration: 36–693 days). At baseline, 89 participants (69.5%; OD: n=36; RP: n=53) had ≥1 target joint. Mean (range) duration of marstacimab treatment was 12.1 (11.5-13.1) months for OD and 11.6 (0.9-12.8) months for RP in the ATP, and 14.0 (1.2-21.8) months for OD and 11.9 (4.9-23.1) months for RP in the LTE. Over the ATP, the OD group reported no serious adverse events (SAEs) vs 1 (2.7%) in the OP; the RP group reported 7 (8.4%) SAEs, of which 1 (1.2%) was treatment-related, vs 2 (2.2%) in the OP. One RP participant discontinued the ATP due to a non-treatment-related SAE. No treatment-related SAEs were reported during the LTE. Antidrug antibodies developed in 23/116 participants (19.8% incidence), of which titers were low and resolved in 22 participants by end of BASIS. No deaths or thromboembolic events were recorded during the ATP or LTE (Table 1). Marstacimab reduced the mean (95% CI) ABR for treated bleeds vs OD (91.6% [88.1-94.1%]) and RP (35.2% [5.6-55.6%]) during the ATP and demonstrated superiority vs OD (P<0.001) and superiority/non-inferiority vs RP (P=0.0376). Overall, mean ABR declined over the first 6 months and continued to decline during the second 6 months of the ATP. The ABR up to 16 months during the LTE was consistent with the ATP for the OD group and reductions continued for the RP group (Table 2). Marstacimab significantly reduced ABR across all secondary bleed categories vs OD and numerically reduced vs RP (non-inferiority). Conclusions: Once-weekly subcutaneous marstacimab was safe and effective for reducing bleeding events in participants with severe HA or moderately severe to severe HB without inhibitors for 12 months in BASIS, and in an additional 16 months in the LTE study.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.