OC 59.3 - Pooled Safety Results from the Multidose explorer Studies of Concizumab in Patients with Haemophilia

Tuesday, June 27, 2023

15:15 – 15:30 ET

Room: 517

Session Available As: Live-Stream and On-Demand

Presenting Author(s)

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

Co-Author(s)

TM

Tadashi Matsushita

Professor
Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan.
Nagoya, Aichi, Japan
Pantep Angchaisuksiri, MD

Professor of Medicine
Division of Hematology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Bangkok, Krung Thep, Thailand
Giancarlo Castaman, MD

Medical Director
Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy
Florence, Toscana, Italy
GE

Galal Eliraqi

Senior International Medical Manager
Novo Nordisk, Søborg, Denmark
Søborg, Hovedstaden, Denmark
KK

Kaan Kavakli

Medical Doctor
Department of Hematology, Ege University Children’s Hospital, Izmir, Turkey
Ege, Izmir, Turkey
MO

Michelle C. Ogden

Medical Writer
Novo Nordisk, Søborg, Denmark
Søborg, Hovedstaden, Denmark
JR

Josephine S. Rasmussen

Safety Surveillance Specialist
Novo Nordisk, 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
AS

Amy Shapiro

Medical Director
Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA
Indianapolis, Indiana, United States
JA

Jan Astermark

Professor, Senior Consultant
Department of Hematology Oncology and Radiation Physics, Skane University Hospital, and Institution of Translational Medicine, Lund University, Malmö, Sweden
Malmö, Skane Lan, Sweden

Background: Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody in development as subcutaneous prophylaxis for patients with any haemophilia subtype.

Aims: To comprehensively analyse pooled safety data from multiple-dose studies in the ‘explorer’ concizumab development programme in patients with haemophilia.

Methods: Results from five multiple-dose studies (explorer3 [phase 1], explorer4 and explorer5 [phase 2], explorer7 and explorer8 [phase 3]) were pooled without adjustments.
Concizumab was administered subcutaneously, daily (phase 2/3 studies) or every 4 days (explorer3).

Results: 320 patients aged 12–79 years were exposed to concizumab, corresponding to 415.0 patient years of exposure (PYE).
241 (75.3%) patients reported 1351 adverse events (AE) (3.3/PYE) (Table 1). The pattern of adverse events was as expected with a subcutaneous treatment within a haemophilia patient population, with most frequently reported AEs being injection-site reactions (23.8%, grouped terms, Figure 1) followed by nasopharyngitis and COVID-19. All injection-site reactions were non-serious, most were mild; one event of moderate injection-site pain led to treatment discontinuation. Safety profile was similar across haemophilia subtypes and age groups.
Three patients in phase 3 studies experienced serious non-fatal thromboembolic events (TEs), leading to permanent treatment discontinuation per protocol. Concizumab treatment was subsequently paused for all participants and restarted with risk mitigations (updated breakthrough bleed treatment guidance and new dosing regimen). No TEs were reported after restart of explorer 7/8.
Two patients experienced hypersensitivity reactions (one serious) leading to permanent treatment discontinuation per protocol.
Other reported treatment-related serious AEs (SAEs) included 3 patients with bleed-related events: one with melaena/haematemesis; two with intraabdominal haemorrhage (one fatal). Remaining single events: dizziness, atypical pneumonia, and increased coagulation parameters (D-dimer, prothrombin fragment 1+2; no TE reported). Excluding the fatality, all patients recovered.

Conclusion(s): Concizumab was overall safe and well-tolerated with a similar safety profile across haemophilia subtypes and age groups.

Learning Objectives:

have an overview of the pooled safety data from multiple-dose studies in the ‘explorer’ concizumab development programme in patients with haemophilia A and B with or without inhibitors.
understand the pattern of frequently reported adverse events and recognise serious treatment related adverse events.
acknowledge that concizumab was overall safe and well tolerated with no thromboembolic events reported after restart of the phase 3 trials.