Hemophilia and Rare Bleeding Disorders
Annette von Drygalski, MD
Director, Hemophilia and Thrombosis Treatment Center
Division of Hematology/Oncology, Department of Medicine, University of California San Diego
San Diego, California, United States
Pratima Chowdary, MD
Professor of Haemostasis and Haematology
Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free Hospital
London, England, United Kingdom
Professor and Director Emerita Pediatric Hematology Oncology
Michigan State University
East Lansing, Michigan, United States
Professor of Haematology
Centre Hospitalier Universitaire de Lille, Université de Lille
Lille, Nord-Pas-de-Calais, France
Barbara A. Konkle, MD
Professor of Medicine
Washington Center for Bleeding Disorders and the University of Washington
Seattle, Washington, United States
Institute of Experimental Hematology and Transfusion Medicine and Centre for Rare Diseases, Universitätsklinikum Bonn
Bonn, Nordrhein-Westfalen, Germany
Davide Matino, MD
Division of Hematology & Thromboembolism, Department of Medicine, McMaster University
Hamilton, Ontario, Canada
Robert Klamroth, MD, PhD
Head of Department of Internal Medicine; Director of the Hemophilia Treatment Center
Vivantes Klinikum, Friedrichshain
Berlin, Berlin, Germany
Angela C Weyand, MD
Clinical Assistant Professor
Division of Hematology/Oncology, Department of Pediatrics, University of Michigan
Ann Arbour, Michigan, United States
Victor Jimenez Yuste
Associate Professor, Head of Hematology Department
Hospital Universitario de La Paz, Autónoma University
Madrid, Madrid, Spain
Global Safety Office, Rare Blood Disorders
Cambridge, Massachusetts, United States
Vice President, Head of Clinical and Translational Science
Stockholm, Stockholms Lan, Sweden
Senior Clinical Research Director, Rare Blood Disorders
Amsterdam, Noord-Holland, Netherlands
Efanesoctocog alfa is a new class of factor VIII (FVIII) replacement designed to overcome the von Willebrand factor-imposed half-life ceiling.
To evaluate the efficacy, safety, and pharmacokinetics of efanesoctocog alfa in previously treated patients, ≥12 years, with severe hemophilia A.
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.
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.