Hemophilia and Rare Bleeding Disorders
Annette von Drygalski, MD
Director, Hemophilia & Thrombosis Treatment Center
University of California San Diego
La Jolla, California, United States
Pratima Chowdary, MD
Consultant Haematologist
Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, United Kingdom
London, England, United Kingdom
Roshni Kulkarni
Physician
Department of Pediatrics and Human Development, Michigan State University, East Lansing, Michigan, USA
East Lansing, Michigan, United States
Sophie Susen
Professor of Haematology
Centre Hospitalier Universitaire de Lille, Université de Lille, Lille, France
Lille, Nord-Pas-de-Calais, France
Barbara A. Konkle, MD
Professor of Medicine
University of Washington
Seattle, Washington, United States
Johannes Oldenburg
Professor, Chairman and Director
University Clinic Bonn AöR, Institute of Experimental Haematology and Transfusion Medicine, Bonn, Germany
Bonn, Nordrhein-Westfalen, Germany
Davide Matino, MD
Assistant Professor
Department of Medicine, Division of Hematology, McMaster University, Hamilton, ON
Hamilton, Ontario, Canada
Robert Klamroth, MD, PhD
Priv. Doz. Dr. med.
Vivantes Klinikum im Friedrichshain, Clinic for Internal Medicine Angiology and Haemostaseology
Berlin, Berlin, Germany
Angela C. Weyand, MD
Associate Professor
University of Michigan
Ann Arbor, Michigan, United States
Victor Jimenez Yuste
Associate Professor, Head of Hematology Department
Hospital Universitario de La Paz, Autónoma University
Madrid, Madrid, Spain
Keiji Nogami
Professor
Nara Medical University, Nara, Japan
Nara, Nara, Japan
Stacey Poloskey
Global Safety Office, Rare Blood Disorders
Sanofi
Cambridge, Massachusetts, United States
Bent Winding
Vice President, Head of Clinical and Translational Science
Sobi
Stockholm, Stockholms Lan, Sweden
Annemieke Willemze
Global Project Head, Efanesoctocog alfa (BIVV001), Rare Blood Disorders Development
Sanofi, Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands
Karin Knobe
Head of Development, Rare Blood Disorders
Sanofi
Chilly-Mazarin, Ile-de-France, France
Efanesoctocog alfa is a new class of factor VIII (FVIII) replacement designed to overcome the von Willebrand factor-imposed half-life ceiling.
Aims:
To evaluate the efficacy, safety, and pharmacokinetics of efanesoctocog alfa in previously treated patients, ≥12 years, with severe hemophilia A.
Methods:
After informed consent, patients on prior FVIII prophylaxis entered Arm A (52 weeks once-weekly intravenous efanesoctocog alfa prophylaxis [50 IU/kg]) (NCT04161495). Patients receiving prior on-demand therapy entered Arm B (26 weeks on-demand efanesoctocog alfa [50 IU/kg], then 26 weeks once-weekly prophylaxis [50 IU/kg]). A subset had enrolled in a 12-month observational pre-study. Primary endpoint was Arm A annualized bleed rate (ABR). Secondary endpoints included observational pre-study versus on-study intra-patient ABR (key secondary), bleed treatment, physical health, pain, joint health, pharmacokinetics, and safety.
Results: One female and 132 males enrolled in Arm A; 26 males in Arm B. Arm A mean (SD) and median (IQR) ABR were 0.71 (1.43) and 0.00 (0.00–1.04), respectively. Intra-patient ABR comparison demonstrated superior bleed protection with efanesoctocog alfa versus prior FVIII prophylaxis (P < 0.001; Figure). Most bleeds (96.7%) resolved with one efanesoctocog alfa injection, and 94.9% of responses were rated excellent/good. Once-weekly efanesoctocog alfa provided high sustained factor activity (Figure) consistent with earlier studies. Efanesoctocog alfa prophylaxis was associated with significant improvements from baseline in physical health (P=0.0001), pain (P=0.0276), and joint health (P=0.0101) at Week 52 (Table). Inhibitor development to FVIII was not detected. The most common treatment-emergent adverse events ( >5% of participants overall) were headache, arthralgia, fall, and back pain.
Conclusion(s):
Once-weekly efanesoctocog alfa prophylaxis was well-tolerated, provided superior bleed protection to prior prophylaxis, and showed clinically meaningful improvements in physical health, pain, and joint health. Efanesoctocog alfa prophylaxis provided high sustained factor activity within normal to near-normal levels ( >40%) for most of the week and >10% at Day 7.
Funding: Sanofi and Sobi.