LB 01.1 - Efanesoctocog Alfa Prophylaxis for Previously Treated Patients <12 Years of Age With Severe Hemophilia A

Sunday, June 25, 2023

10:45 – 11:00 ET

Room: 517

Session Available As: Live-Streamed and On-Demand

Presenting Author(s)

Lynn Malec, MD, MSc

Senior Medical Director
Versiti Blood Research Institute, Milwaukee, WI, USA; Division of Hematology & Oncology, Departments of Medicine and Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
Milwaukee, Wisconsin, United States

Co-Author(s)

Flora Peyvandi, MD, PhD (she/her/hers)

Director
IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy
Milano, Lombardia, Italy
Anthony KC. Chan, MBBS

Professor
McMaster University, McMaster Children’s Hospital, Hamilton, Canada
Hamilton, Ontario, Canada
Christoph Koenigs, Dr. Dr.

Professor
University Hospital Frankfurt, Department of Paediatrics and Adolescent Medicine, Frankfurt, Germany
Frankfurt, Hessen, Germany
Bulent Bulent Zulfikar, MD

Professor
Department of Pediatric Hematology, Istanbul University Oncology Institute, Inherited Bleeding Disorders Center, Istanbul, Turkey
Istanbul, Istanbul, Turkey
HY

Huixing Yuan

Statistical Study Lead
Sanofi, Cambridge, MA, USA
Cambridge, Massachusetts, United States
MS

Mindy L. Simpson

Medical Director
Rush University Medical Center, Rush Hemophilia and Thrombophilia Center, Chicago, IL, USA
chicago, Illinois, United States
Maria Teresa Alvarez-Román, MD, PhD

Associate Professor
Department of Hematology, University Hospital La Paz, Autonoma University of Madrid, Madrid, Spain
Madrid, Madrid, Spain
Manuel Carcao, MD, FRCPC

Professor
Division of Haematology/Oncology, Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada
Toronto, Ontario, Canada
JS

Janice M. Staber

Associate Professor
Divison of Hematology/Oncology, Department of Pediatrics, Carver College of Medicine, University of Iowa Stead Family Children’s Hospital, Iowa City, IA, USA
Iowa City, Iowa, United States
AD

Amy L. Dunn

Director
Oncology and Bone Marrow Transplant, Nationwide Children's Hospital and The Ohio State University College of Medicine, OH, USA
Ohio, Ohio, United States
SC

Sheng-Chieh Chou

Director
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Taipei, Taipei, Taiwan (Republic of China)
Roseline d'Oiron, MD

Director
Centre for Haemophilia and Rare Congenital Bleeding Disorders, Bicêtre Hospital AP-HP, University of Paris-Saclay and UMR_S1176 INSERM, Le Kremlin-Bicêtre, France
Le Kremlin-Bicetre, France
MA

Manuela Albisetti

Director
University Children’s Hospital Zurich, Zurich, Switzerland
Zürich, Zurich, Switzerland
MD

Marek Demissie

Senior Clinical Research Director
Sanofi, Cambridge, Massachusetts, United States
Cambridge, Massachusetts, United States
ES

Elena Santagostino

VP Medicine Development Lead for Haemophilia
Sobi, Basel, Switzerland
Basel, Stockholms Lan, Sweden
AY

Abhimanyu Yarramaneni

Global Safety Officer
Sanofi, Bridgewater, NJ, USA
Bridgewater, New Jersey, United States
LA

Lydia Abad-Franch

VP Head of Global Medical Affairs & Clinical Sciences
Sobi, Basel, Switzerland
Basel, Basel-Stadt, Switzerland
SG

Sriya Gunawardena

Senior Clinical Research Director
Sanofi, Bridgewater, NJ, USA
Bridgewater, New Jersey, United States
KF

Karin Fijnvandraat

Professor
Amsterdam UMC, University of Amsterdam, Emma Children’s Hospital, Pediatric Hematology Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands

Background: Efanesoctocog alfa is a new class of high sustained factor VIII (FVIII) replacement therapy designed to overcome the von Willebrand factor-imposed half-life ceiling. In the pivotal XTEND-1 study, once-weekly efanesoctocog alfa 50 IU/kg provided normal to near-normal FVIII activity (>40 IU/dL) for most of the week and superior bleed protection versus prestudy prophylaxis in previously treated patients (PTP; ≥12 years) with severe hemophilia A.

Aims: To evaluate the safety, efficacy, and pharmacokinetics (PK) of efanesoctocog alfa in PTP ( < 12 years) with severe hemophilia A (XTEND-Kids, NCT04759131).

Methods: Patients received once-weekly efanesoctocog alfa 50 IU/kg for 52 weeks. The primary endpoint was the incidence of FVIII inhibitor development. Secondary endpoints included PK, annualized bleed rates (ABRs), efficacy for bleed treatment and perioperative management, and safety.

Results: Seventy-four male PTPs participated ( < 6 years n=38; 6– < 12 years n=36). The mean (SD) efficacy period was 49.81 (6.61) weeks. Inhibitors to FVIII were not detected (0% [95% confidence interval (CI)] 0–4.9]). The mean half-life was 40.2 hours, with mean FVIII activity >40 IU/dL for 3 days, >15 IU/dL for ~5 days, and >10 IU/dL for ~7 days at steady state (Figure). Median (interquartile range) and mean ABRs (95% CI) were 0.00 (0.00–1.02) and 0.89 (0.56–1.42), respectively (Table). Most bleeds resolved with a single 50 IU/kg dose, and response to treatment was excellent/good for 98% of evaluated injections. Perioperative hemostasis was excellent in both major surgeries. Nine patients experienced ≥1 serious treatment-emergent adverse event. No adverse events led to treatment discontinuation.

Conclusion(s): Once-weekly efanesoctocog alfa was well tolerated and provided highly effective bleed protection and treatment in children with severe hemophilia A. High sustained factor activity was within normal to near-normal levels (>40%) for 3 days and at ~10% at Day 7. FVIII inhibitor development was not detected.

Funded by Sanofi and Sobi.