OC 01.4 - Interim analysis of joint outcomes in adult and adolescent patients with severe hemophilia A receiving efanesoctocog alfa during the phase 3 XTEND-ed long-term extension study

Saturday, June 22, 2024

13:45 – 14:00 ICT

Room: Ballroom B1

Presenting Author(s)

Annette von Drygalski, MD, PharmD, RMSK

Professor of Clinical Medicine
University of California San Diego
San Diego, California, United States

Co-Author(s)

CK

Christoph Königs

Clinical and Molecular Hemostaseology Research Laboratory and Clinical Studies Manager
Goethe University Frankfurt, University Hospital, Department of Pediatrics and Adolescent Medicine, Frankfurt, Germany
Frankfurt, Hessen, Germany
Barbara A. Konkle

Professor of Medicine
Washington Center for Bleeding Disorders and the University of Washington, Seattle, WA, USA
Seattle, Washington, United States
Cedric Hermans, MD, FRCP, PhD

Head of the Division of Haematology, the Hemostasis and Thrombosis Unit, and the Hemophilia Center
Saint-Luc University Hospital
Saint-Luc, Brussels Hoofdstedelijk Gewest, Belgium
LK

Liane Khoo

Director
Institute of Haematology, Royal Prince Alfred Hospital, Sydney, Australia
Sydney, New South Wales, Australia
Kathelijn Fischer

Pediatric Hematologist
Centre for Benign Haematology, Thrombosis and Haemostasis, Van Creveldkliniek, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
Utrecht, Utrecht, Netherlands
NS

Nobuaki Suzuki

Service Lecturer
Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan
Aichi, Aichi, Japan
HG

Hailing Guo

Biostatistician
Sanofi, Bridgewater, NJ, USA
Bridgewater, Massachusetts, United States
UK

Umer Khan

Biostatistics Lead
Sanofi, Cambridge, MA, USA
Cambridge, Massachusetts, United States
LB

Linda Bystrická

Senior Director, Global Medical Affairs
Sobi, Basel, Switzerland
Basel, Basel-Stadt, Switzerland
AF

Alejandro Fernandez

Medical Director
Sanofi, Zurich, Switzerland
Zurich, Zurich, Switzerland
ES

Elena Santagostino

VP, Medicine Development Lead Haemophilia
Sobi, Basel, Switzerland
Basel, Basel-Stadt, Switzerland
LM

Lara Mamikonian

Clinical Research Director
Sanofi, Cambridge, MA, USA
Cambridge, Massachusetts, United States
Robert Klamroth, MD

Head of Department
Vivantes Klinikum, Friedrichshain, Berlin, Germany
Berlin, Berlin, Germany

Background: Hemophilic arthropathy and chronic joint pain from repeated bleeding episodes in hemophilia A may occur despite standard-of-care prophylaxis. In XTEND-1 (NCT04161495), once-weekly efanesoctocog alfa (50 IU/kg) prophylaxis was well tolerated, providing highly effective bleed protection and high-sustained factor VIII activity levels across the weekly dosing interval.

Aims: Assess long-term joint health with efanesoctocog alfa prophylaxis in adults/adolescents from XTEND-1 who continued to the extension study, XTEND-ed (NCT04644575).

Methods: XTEND-ed is an open-label, multicenter study of previously treated patients with severe hemophilia A. Participants provided informed consent; the study was approved by applicable review boards. Changes from parent study (XTEND-1) baseline to Month 12 in XTEND-ed in Hemophilia Joint Health Scores (HJHS) and target joint resolution for participants aged ≥12 years who received once-weekly efanesoctocog alfa (50 IU/kg) prophylaxis are presented descriptively (data cutoff June 8, 2023). Individual joints (left/right elbows, knees, and ankles) were scored according to 8 HJHS domains; gait was also assessed. Total HJHS score encompasses joint and gait score. Target joints were evaluated based on International Society on Thrombosis and Haemostasis criteria.

Results: Arm A of XTEND-ed enrolled 146 participants from XTEND-1 (additional mean [standard deviation, SD] treatment duration 82.5 [14.3] weeks). By Month 12 in XTEND-ed, joint health had improved or been maintained in evaluable participants compared with XTEND-1 baseline, as measured by HJHS total score, total joint score, and subdomain scores (Figure, Table). The HJHS domain with the greatest mean (SD) change from baseline to Month 12 was flexion loss -0.6 (2.7). At XTEND-1 baseline, there were 140 target joints among 45 participants; at 1 year, all target joints (n=132) had resolved in participants exposed for ≥12 months (n=43).

Conclusion(s): Interim results from XTEND-ed indicate that once-weekly prophylaxis with efanesoctocog alfa is associated with improvement or maintenance of joint health in adults and adolescents.
Funded by Sanofi and Sobi.