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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Concizumab Efficacy in Patients With Hemophilia A/B Without Inhibitors from the Phase 3 explorer8 Study: A Post-hoc Sensitivity Analysis for the Intra-patient Comparison of Concizumab With Previous Prophylaxis Anthony KC Chan1, Hermann Eichler2, Julien Bovet3, Renée Brown Frandsen3, Allison P Wheeler4, Emily Waters5, Pratima Chowdary6, Leandra LePorte5. 1Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton, ON, Canada.2Institute of Clinical Hemostaseology and Transfusion Medicine, Saarland University and University Hospital, Homburg, Germany.3Novo Nordisk A/S, Søborg, Denmark.4Division of Pediatric Hematology/Oncology & Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WA, USA.5Novo Nordisk Inc., Plainsboro, NJ, USA.6Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, and Department of Haematology, Cancer Institute, University College London, London, United Kingdom |
Abstract
Background: Concizumab, a subcutaneous monoclonal antibody targeting tissue factor pathway inhibitor, is approved for prophylaxis in hemophilia A/B with or without inhibitors. In the phase 3 explorer8 study (NCT04082429), concizumab demonstrated superior efficacy versus on-demand treatment. A subset of patients was included with the aim of showing non-inferiority of concizumab to previous prophylaxis; however, this was not confirmed. A data review showed that extreme ABRs in 3 patients influenced the mean ABR. Objectives: A post-hoc sensitivity analysis was performed to investigate the impact of the extreme ABRs on the intra-patient comparison of concizumab to previous prophylaxis. Methods: Male patients (≥12 years) were assigned to one of four arms in explorer8. A subset of patients in a non-randomized arm were included in the intra-patient analysis. Patients received a 1.0 mg/kg concizumab loading dose followed by 0.20 mg/kg daily with potential dose adjustment to 0.15 or 0.25 mg/kg based on concizumab plasma concentration. Sensitivity analyses using imputation were performed to investigate the impact of the extreme ABRs at the 32-week cut-off (defined as when patients receiving concizumab prophylaxis had completed the visit after 32 weeks, or permanently discontinued treatment). Treated spontaneous and traumatic bleeding episodes for the three patients with extreme ABRs were replaced by imputed values computed from the remaining patients. Sensitivity analyses were conducted using parametric (negative binomial regression models) and non-parametric (Wilcoxon signed-rank test) approaches. Results: The sensitivity analyses included all patients in the intra-patient analysis set (HA n=29; HB n=22). Among these patients, 38 (74.5%) were White, 12 (23.5%) were Asian, and 1 (2.0%) was Black. For HA, the analysis using imputed values for the three patients with extreme ABRs showed that the estimated mean ABR (95% CI) for concizumab decreased from 5.1 (2.71; 9.65) to 2.8 (1.76;4.57) upon analysis using the negative binomial regression. The ABR ratio (95% CI) of concizumab vs previous prophylaxis reduced from 1.39 (0.73; 2.63) to 0.75 (0.40; 1.42). For HB, the estimated mean ABR for concizumab decreased from 5.4 (2.27; 12.91) to 3.1 (1.80; 5.37) and the ABR ratio (95% CI) of concizumab vs previous prophylaxis reduced from 1.75 (0.81; 3.78) to 1.00 (0.58; 1.73). For both HA/HB, the upper limits of the 95% CIs were below the non-inferiority margin of 2.0. Wilcoxon signed-rank tests showed that ‘no difference’ could not be rejected between median ABRs for concizumab and previous prophylaxis with imputed data for both HA/HB. Conclusions: Post-hoc sensitivity analyses using imputed data for the three patients in the explorer8 intra-patient comparison subset who had extreme ABRs showed that the upper limit of the 95% CI of the ABR ratios decreased below the non-inferiority margin of 2.0 when comparing concizumab to previous prophylaxis. This indicates that, for most patients, ABRs during concizumab demonstrated non-inferiority when compared to prior prophylaxis regimens. As with any therapy, there may be variability in individual responses to treatment. Overall, the explorer8 study showed that once-daily, subcutaneous concizumab prophylaxis was efficacious and well-tolerated. Previously presented at ASH 2025, Orlando, Florida, 6–9 December 2025.
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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.