PB1174 - Eptacog beta for resolution of bleeding episodes in patients with hemophilia A or B with inhibitors: Efficacy and safety according to inhibitor titer

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Dan P. Hart, BSc, MBChB, MRCP, FRCPath

Senior Clinical Lecturer in Haematology & Honorary Consultant in Haematology
The Royal London Hospital Haemophilia Centre, Barts and The London School of Medicine and Dentistry
London, England, United Kingdom

Co-Author(s)

Robert F. Sidonio, Jr., MD, MSc

Associate Professor of Pediatrics
Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine
Atlanta, Georgia, United States
YA

Yasmina Abajas

Clinical Assistant Professor
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
SA

SANJAY AHUJA

Director - Hemophilia Program
University Hospitals Health System, Cleveland, OH
Cleveland, Ohio, United States
María Teresa Alvarez-Román, MD, PhD

Head of the Thrombosis and Haemostasis Unit
La Paz University Hospital, Madrid, Spain
Madrid, Madrid, Spain
Manuel Carcao, MD, FRCPC

Director, Haemophilia Clinic and Haemostasis Program
Hospital for Sick Children, Toronto, Canada
Toronto, Ontario, Canada
YD

Yesim Dargaud

Director Hemostasis Unit
Hôpital Cardiologique Louis Pradel, Université Lyon 1
Lyon, Rhone-Alpes, France
Miguel Escobar, MD

Professor of Medicine, Medical Director
University of Texas Health Science Center of Houston, McGovern Medical School, Gulf States Hemophilia and Thrombophilia Center, Houston, Texas
Houston, Texas, United States
Craig Kessler, MD

Professor of Medicine and Pathology and Section Chief of Hematology
Georgetown University Hospital
Washington DC, Washington, United States
OK

Osman Khan

Associate Professor, Interim Section Chief, Pediatric Hematology/Oncology
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
CL

Cindy Leissinger

Adult Hematologist
Tulane University
New Orleans, California, United States
PM

Philip Maes

Head of Clinic
Antwerp University Hospital
Egedem, Antwerpen, Belgium
Maria Elisa Mancuso, MD, PhD

Senior Consultant in Haematology
IRCCS Humanitas Research Hospital
Milan, Lombardia, Italy
AM

Abraham Majluf-Cruz

Medical chief
Unidad médica de investigación de trombosis, hemostasia y aterogénesis, Instituto Mexicano del Seguro Social
Mexico City, Distrito Federal, Mexico
Wolfgang Miesbach, MD

Professor and Head of Coagulation Disorders and Comprehensive Care Centre
University Hospital Frankfurt, Frankfurt, Germany
Frankfurt, Hessen, Germany
MS

Mindy L. Simpson

Pediatric Hematologist-Oncologist
Rush University medical Center
chicago, Illinois, United States
Michael Wang, MD

HTC Clinical Director
University of Colorado Denver Hemophilia and Thrombosis Center
Aurora, Colorado, United States
CM

Christopher Macie

Senior Medical Director
HEMA Biologics
Louisville, Kentucky, United States
HW

Hongying Wang

Director Biostatistics
LFB-USA
Framingham, Massachusetts, United States
Alok Srivastava, MD, FRACP, FRCPA, FRCP

Professor of Medicine
Christian Medical College, Vellore, India
Vellore, Tamil Nadu, India

Background: Eptacog beta (LFB/HEMA Biologics) is a new bypassing agent approved in the US for treatment of bleeding episodes (BEs) in patients with hemophilia A/B with inhibitors (PwHABI) aged ≥12 years.

Aims: To evaluate eptacog beta for treatment of BEs according to low ( < 5 BU) or high (≥5 BU) inhibitor titer.

Methods: This analysis pertains to PERSEPT 1, a phase 3 study performed by LFB in PwHABI aged ≥12 years (NCT02020369). IEC/IRB approvals and informed consent were obtained. PwHABI received eptacog beta for treatment of BEs at an initial dose of 75 or 225μg/kg, followed by 75μg/kg at predefined intervals over 24 hours. The primary endpoint (EMA definition) was the proportion of successfully treated BEs (i.e., ‘good’/‘excellent’ response), irrespective of BE severity, 12 hours after initial dose.

Results: Twenty-seven patients with 468 BEs were analyzed (low-titer subgroup, 218 BEs; high-titer subgroup, 250 BEs) (Table 1). The proportion (95%CI) of successfully treated BEs at 12 hours with 75 and 225µg/kg initial dose regimens (IDRs), respectively, was 75.2% (63.6–86.8) versus 87.1% (79.8–94.5) in the low-titer subgroup (p=0.006), and 94.6% (88.2–100) versus 100% (100–100) in the high-titer subgroup (p=0.034) (Figure 1). Corresponding results at 24 hours were 96.4% (91.5–100) versus 99.0% (97.1–100) in the low-titer subgroup (p=0.118), and 96.9% (92.4–100) versus 100% (100–100) in the high-titer subgroup (p=0.125). Two patients in the low-titer subgroup experienced seven treatment-related adverse events (infusion site discomfort [n=4]; infusion site hematoma [n=2]; body temperature increase [n=1]). None occurred in the high-titer subgroup. No thromboembolic events, hypersensitivity reactions, or deaths were reported. No eptacog beta neutralizing antibodies were detected.

Conclusion(s): Both eptacog beta IDRs achieved successful resolution of BEs in PwHABI irrespective of inhibitor titer with a higher response rate for 225μg/kg IDR at 12 hours. No safety issues were noted.