OC 59.1 - Concizumab prophylaxis in patients with haemophilia A or B without inhibitors: Efficacy and safety results from the primary analysis of the phase 3 explorer8 study

Tuesday, June 27, 2023

14:45 – 15:00 ET

Room: 517

Session Available As: Live-Stream and On-Demand

Presenting Author(s)

PC

Pratima Chowdary, MD

Consultant Haematologist
Katharine Dormandy Haemophilia and Thrombosis Centre, Royal Free London NHS Foundation Trust, London, United Kingdom
London, England, United Kingdom

Co-Author(s)

Pantep Angchaisuksiri, MD

Professor of Medicine
Division of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Bangkok, Krung Thep, Thailand
SA

Shashikant Apte

Director
Sahyadri Speciality Hospital, Pune, Maharashtra, India
Pune, Maharashtra, India
Anthony KC. Chan, MBBS

Professor
McMaster University, McMaster Children’s Hospital, Hamilton, Canada
Hamilton, Ontario, Canada
SJ

Sanja H. Jacobsen

Senior Statistician
Novo Nordisk A/S, Søborg, Denmark
Søborg, Hovedstaden, Denmark
VJ

Victor Jiménez Yuste

Associate Professor of Hematology
Haematology Department, La Paz University Hospital, IdiPAZ, Universidad Autónoma Madrid, Madrid, Spain
Madrid, Madrid, Spain
JT

Jay Jay Thaung Zaw

International Medical Manager
Novo Nordisk A/S, Søborg, Denmark
Søborg, Hovedstaden, Denmark
AW

Allison P. Wheeler

Associate Professor in Pediatrics
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
Nashville, Tennessee, United States
Jerzy Windyga, Prof. dr med. (he/him/his)

Head Department of Hemostasis Disorders and Internal Medicine
Institute of Hematology and Transfusion Medicine
Warsaw, Mazowieckie, Poland
Hermann Eichler, MD (he/him/his)

Professor of Transfusion Medicine and Haemostaseology
Institute of Clinical Haemostaseology and Transfusion Medicine, University and University Hospital of the Saarland, Homburg, Germany
Homburg, Saarland, Germany

Background: Concizumab (anti-tissue factor pathway inhibitor antibody) is in development as once-daily subcutaneous prophylaxis for all haemophilia subtypes. explorer8 (NCT04082429) primary analysis results are presented.

Aims: Assess concizumab efficacy/safety in patients with haemophilia A/B without inhibitors (HA/HB).

Methods: Informed consent/ethics committee approval were obtained. Patients with HA and HB were randomised 1:2 to no prophylaxis (arm 1; ≥24 weeks) or concizumab prophylaxis (arm 2; ≥32 weeks) or assigned to non-randomised concizumab prophylaxis (arms 3&4). Safety was assessed, and treatment was paused (2020/03 – 2020/08) due to non-fatal thromboembolic events in two patients and restarted after mitigation measures including a revised dosing regimen. The primary analysis compared the number of treated spontaneous/traumatic bleeding episodes between no prophylaxis and concizumab prophylaxis (arm 1 versus arm 2) by negative binomial regression. The confirmatory secondary analysis compared the number of treated spontaneous/traumatic bleeding episodes in a subset of arm 4 patients in explorer8 versus their previous standard-of-care prophylaxis in explorer6 (NCT03741881) during stable treatment (non-inferiority was confirmed if the upper limit of 95% confidence interval [CI] for annualised bleeding rate [ABR] ratio was < 2.0; negative binomial regression).

Results: The study included 148 patients after treatment restart. Superiority of concizumab over no prophylaxis was met (Table 1). For HA, the estimated mean ABR [95% CI] on concizumab versus no prophylaxis was 2.7 [1.6–4.6] versus 19.3 [11.3–33.0], respectively (ABR ratio: 0.14 [0.07–0.29]; P< 0.001), and for HB, 3.1 [1.9–5.0] versus 14.8 [8.1–26.9], respectively (ABR ratio: 0.21 [0.10–0.45]; P< 0.001). Non-inferiority of concizumab to previous prophylaxis was not confirmed (ABR ratios: HA, 1.4 [0.7–2.6]; HB, 1.8 [0.8–3.8]), with numerically comparable (HA) or lower (HB) median ABRs (Table 2). There was no thromboembolic event after treatment restart.

Conclusion(s): Concizumab prophylaxis was effective in reducing the ABR compared with no prophylaxis in both HA/HB and considered safe and well-tolerated.

Learning Objectives:

Understand that concizumab prophylaxis was effective when compared to no prophylaxis.
Understand that the current dosing regimen and bleed management strategies have not demonstrated any thrombotic events.
Understand that concizumab has the potential to be one of the first subcutaneous treatment option for haemophilia B given the confirmed superiority of concizumab prophylaxis compared with no prophylaxis in phase 3 clinical studies.