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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Subcutaneous Four-Week Dosing of the Novel Protein S Antibody VGA039 Demonstrates Safety and Clinically Meaningful Bleed Reduction in Patients with Von Willebrand Disease: Phase 1/2 Multi-Dose Study Results Nicoletta C.Machin1, Shrinath Kshirsagar2, Adam Giermasz3, Johnny Mahlangu4, Gabriela Yamaguti-Hayakawa5, Savita Rangarajan6, Genevieve Moyer7, Christine Kempton8, Jane Mason9, Michelle Sholzberg10, Paula Villaça11, Sandip Panicker12, Eileen K.Sawyer12, Gary Patou12, Benjamin Kim12, Allison P.Wheeler13. 1Division of Classical Hematology, Department of Medicine, University of Pittsburgh and Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA.2Advanced Center for Oncology, Haematology & Rare Disorders, K.J.Somaiya Medical College & Research Center, Somaiya Ayurvihar, Mumbai, India.3Division of Hematology/Oncology, Department of Medicine, University of California Davis, Sacramento, CA, USA.4Haemophilia Comprehensive Care Centre, Charlotte Maxeke Johannesburg Hospital, University of the Witwatersrand, Johannesburg, South Africa.5Hemocentro UNICAMP, University of Campinas, Campinas, Brazil.6University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.7The University of Colorado Hemophilia and Thrombosis Center, Aurora, CO, USA.8Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA.9Queensland Haemophilia Centre, Department of Haematology and BMT, Royal Brisbane and Women’s Hospital, Brisbane, Australia.10Departments of Medicine, and Laboratory Medicine and Pathobiology, St.Michael's Hospital, University of Toronto, Toronto, ON, Canada.11Hospital das Clínicas, University of São Paulo, São Paulo, Brazil.12Star Therapeutics, Inc., South San Francisco, CA, USA.13Washington Center for Bleeding Disorders and Divisions of Pediatric Hematology/Oncology and Hematology/Oncology, University of Washington, Seattle, WA, USA |
Abstract
Background: Von Willebrand disease (VWD) causes recurrent and prolonged bleeding, leading to clinical sequelae and high treatment burden due to the need for frequent infusions. VGA039 is a fully human IgG4 monoclonal antibody that inhibits Protein S cofactor activity, thereby enhancing thrombin generation and promoting primary and secondary hemostasis. In a prior single-ascending-dose study, VGA039 was safe and associated with a reduction in bleeding events. Objective: This multi-dose study evaluated the safety, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneous (SC) VGA039 prophylaxis in patients with all types of VWD. Methods: This open-label, phase 1/2 study (NCT05776069) was conducted in symptomatic participants aged 12-60 years with any type of VWD. Key eligibility criteria included baseline FVIII activity less than the lower limit of normal and no laboratory evidence of thrombophilia or history of thromboembolism. Participants received scheduled doses of SC VGA039 over 120 days with up to 42-day follow up and optional participation in an open-label extension study. Safety, efficacy, pharmacokinetic, and pharmacodynamic parameters were collected. Results: As of November 14, 2025, a total of 16 participants (aged 15-53 years, weighing 45-160.5 kg) with various VWD types received a single SC loading dose on Day 1, followed by up to 5 SC maintenance doses every 4 weeks starting on Day 8. Six participants in Cohort MD-1 received a flat dose of 225 mg SC VGA039. Ten participants in Cohort MD-2 received weight-banded doses of SC VGA039 per the following criteria: 187.5 mg (45–<60 kg; n=0), 262.5 mg (60–100 kg; n=7), or 450 mg (>100 kg; n=3). There were no serious drug-related AEs or clinically significant elevations in D-dimer levels. VGA039 achieved plasma concentrations consistent with the anticipated therapeutic range. Increase in thrombin generation was observed in the interim analysis. Efficacy was analyzed in participants (n=8) who completed the treatment period demonstrating reductions of 41-100%. All participants completing the study elected to continue in the open-label extension study. Conclusions: VGA039 administered subcutaneously every four weeks was safe, well tolerated, and associated with clinically meaningful reductions in bleeding across VWD subtypes in this interim analysis. These findings support the ongoing Phase 3 trial (NCT07115004).
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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.