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Presentation Details
| Bleed Treatment Outcomes from the XTEND-ed Study in Patients Aged 50 Years and Older Johannes Oldenburg1, Barbara Konkle2, Toshko Lissitchkov3, Pratima Chowdary4, Liane Khoo5, Katsuyuki Futatake6, Elena Santagostino7, Helena Palmborg8, Linda Bystrická7, Jennifer Dumont9, Meredith Foster9, Sriya Gunawardena10, Andrew Wilson10, Annette von Drygalski11, Scott Cleland10. 1University Hospital Bonn, Bonn, Germany.2Washington Center for Bleeding Disorders, University of Washington, Washington, WA, USA.3Specialized Hospital for Active Treatment of Hematological Diseases, Department of Chemotherapy, Hemotherapy and Hereditary Blood Diseases at Clinical Hematology Clinic, Sofia, Bulgaria.4Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital, London, United Kingdom.5Royal Prince Alfred Hospital, NSW Health Pathology, Sydney, Australia.6Ogikubo Hospital, Tokyo, Japan.7Sobi, Basel, Switzerland.8Sobi, Stockholm, Sweden.9Sanofi, Cambridge, MA, USA.10Sanofi, Morristown, NJ, USA.11Division of Hematology/Oncology, Department of Medicine, University of California, San Diego, CA, USA |
Abstract
Background: Efanesoctocog alfa is a first-in-class high sustained factor VIII replacement therapy designed to decouple recombinant factor VIII from endogenous von Willebrand factor. In XTEND-1 (NCT04161495), once-weekly efanesoctocog alfa provided superior bleed prevention over prior FVIII prophylaxis and was well tolerated in adults and adolescents with severe haemophilia A. Patients completing XTEND-1 could enter Arm A of the extension study, XTEND-ed (NCT04644575). Objectives Older adults with haemophilia A face complex medical challenges due to aging that are compounded by limited data in this population. We conducted a post-hoc analysis of data from patients aged ≥50 years through the second interim analysis of XTEND-ed (datacut: February 22, 2024).
Methods: Patients received efanesoctocog alfa once weekly (50 IU/kg). Exploratory endpoints included bleed treatment, factor consumption, annualized bleeding rates (ABRs), Hemophilia Joint Health Score (HJHS), PROMIS Pain Intensity 3a T-score, Hemophilia Quality of Life (QoL) Questionnaire for Adults (physical health), and safety outcomes.
Results: Thirty-two patients (1 female) aged ≥50 years were enrolled in XTEND-ed (mean age [SD; range], 58.5 [6.6; 50.0–74.0] years; 15 had target joints at XTEND-1 baseline. Twenty-five patients (78.1%) used concomitant medications; common medication classes included analgesics (opioid and non-opioid), antibiotics, and antihypertensives. Median (range) efficacy period and treatment duration in XTEND-ed were 115.4 (31.3–136.6) and 120.1 (31.3–136.6) weeks, respectively. Median (range) number of injections per patient was 121.5 (30.0–146.0), and weekly routine prophylaxis dose was 51.1 (47.2–53.2) IU/kg. Mean (95% CI) model-based ABRs during the efficacy period were: overall, 0.92 (0.54, 1.55); spontaneous, 0.38 (0.19, 0.75); traumatic, 0.29 (0.15, 0.54). In the 0–12-month and 13–24-month periods, 13 (43.3%) and 10 (34.5%) treated bleeds were spontaneous; 7 (23.3%) and 11 (37.9%) were traumatic. Most occurred in joints and muscle. Most bleeds (0–12 months: 90% [n=27]; 13–24 months: 96.6% [n=28]) were resolved with 1 injection; the remainder required 2 injections. The number of bleeding episodes/patient by 12-month interval is shown in Figure 1. Mean (SD) change in HJHS score from XTEND-1 baseline was -4.1 (10.6) and -3.2 (10.7) points to XTEND-ed Months 12 and 24, respectively. Improvement in pain intensity and QoL from XTEND-1 baseline was maintained to XTEND-ed Month 24. Treatment-emergent adverse events (TEAEs) were reported in 26/32 (81.3%) patients during the efficacy period (one treatment-related); ≥1 serious TEAEs were reported in 6 (18.8%) patients (none were treatment-related). No TEAEs resulted in treatment discontinuation or death. No inhibitor development occurred.
Conclusions: Results of this post hoc analysis in patients aged ≥50 years in the XTEND-ed study show that efanesoctocog alfa provides highly effective bleed protection and improvements in patient-reported outcomes without any new safety signals.
Funding: Study funded by Sanofi and Sobi.
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.
Methods: Patients received efanesoctocog alfa once weekly (50 IU/kg). Exploratory endpoints included bleed treatment, factor consumption, annualized bleeding rates (ABRs), Hemophilia Joint Health Score (HJHS), PROMIS Pain Intensity 3a T-score, Hemophilia Quality of Life (QoL) Questionnaire for Adults (physical health), and safety outcomes.
Results: Thirty-two patients (1 female) aged ≥50 years were enrolled in XTEND-ed (mean age [SD; range], 58.5 [6.6; 50.0–74.0] years; 15 had target joints at XTEND-1 baseline. Twenty-five patients (78.1%) used concomitant medications; common medication classes included analgesics (opioid and non-opioid), antibiotics, and antihypertensives. Median (range) efficacy period and treatment duration in XTEND-ed were 115.4 (31.3–136.6) and 120.1 (31.3–136.6) weeks, respectively. Median (range) number of injections per patient was 121.5 (30.0–146.0), and weekly routine prophylaxis dose was 51.1 (47.2–53.2) IU/kg. Mean (95% CI) model-based ABRs during the efficacy period were: overall, 0.92 (0.54, 1.55); spontaneous, 0.38 (0.19, 0.75); traumatic, 0.29 (0.15, 0.54). In the 0–12-month and 13–24-month periods, 13 (43.3%) and 10 (34.5%) treated bleeds were spontaneous; 7 (23.3%) and 11 (37.9%) were traumatic. Most occurred in joints and muscle. Most bleeds (0–12 months: 90% [n=27]; 13–24 months: 96.6% [n=28]) were resolved with 1 injection; the remainder required 2 injections. The number of bleeding episodes/patient by 12-month interval is shown in Figure 1. Mean (SD) change in HJHS score from XTEND-1 baseline was -4.1 (10.6) and -3.2 (10.7) points to XTEND-ed Months 12 and 24, respectively. Improvement in pain intensity and QoL from XTEND-1 baseline was maintained to XTEND-ed Month 24. Treatment-emergent adverse events (TEAEs) were reported in 26/32 (81.3%) patients during the efficacy period (one treatment-related); ≥1 serious TEAEs were reported in 6 (18.8%) patients (none were treatment-related). No TEAEs resulted in treatment discontinuation or death. No inhibitor development occurred.
Conclusions: Results of this post hoc analysis in patients aged ≥50 years in the XTEND-ed study show that efanesoctocog alfa provides highly effective bleed protection and improvements in patient-reported outcomes without any new safety signals.
Funding: Study funded by Sanofi and Sobi.
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.