PB1458 - Thromboembolic (TE) Events in Cold Agglutinin Disease (CAD): Post-hoc Analysis PRE- and ON-sutimlimab Treatment in the Phase 3 CARDINAL and CADENZA Studies

Tuesday, June 27, 2023

18:30 – 19:30 ET

Room: Exhibition

Co-Author(s)

AR

Alexander Röth

Senior Physician
University Hospital Essen, Germany
Essen, Nordrhein-Westfalen, Germany

Co-Author(s)

YU

Yasutaka Ueda

Assistant Professor
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Japan
Osaka, Osaka, Japan
KM

Keith R. McCrae

Director. Benign Hematology, Taussig Cancer Institute
Cleveland Clinic Foundation, Cleveland, OH, USA
Clevelend, Ohio, United States
UK

Umer Khan

Biostatistics Lead
Sanofi, San Diego, CA, USA
San Diego, California, United States
KK

Katarina Kralova

Global Safety Officer
Sanofi, Paris, France
Paris, Ile-de-France, France
MW

Marek Wardȩcki

Clinical Research Director
Sanofi, Warsaw, Poland
Warsaw, Mazowieckie, Poland
FS

Frank Shafer

Senior Clinical Research Director, Complement Biology Therapeutics
Sanofi, Bridgewater, NJ, USA
Bridgewater, New Jersey, United States

Presenting Author(s)

Ronnie Yoo, PhD

Life Science Management Director, Global Medical
Sanofi, Cambridge, MA, US
Cambridge , Massachusetts, United States

Co-Author(s)

Catherine M. Broome, PhD

Clinician
Department of Medicine, Georgetown University
Washington, DC, District of Columbia, United States

Background: Cold agglutinin disease (CAD), a rare chronic autoimmune hemolytic anemia mediated by classical complement pathway activation, is associated with increased risk of thromboembolic (TE) events compared with the general population. Sutimlimab inhibits complement C1s, providing a therapeutic approach for CAD.

Aims: To assess the TE events PRE- and ON-sutimlimab treatment from the Phase 3 CARDINAL (NCT03347396) and CADENZA (NCT03347422) studies.

Methods: TE event analysis included participants who had initiated sutimlimab, had a CAD diagnosis date, and had a treatment start and end date. TE events recorded during the study were medically adjudicated before inclusion. ON-sutimlimab events include all events from treatment initiation until 17 days post last dose of sutimlimab. PRE-sutimlimab and ON-sutimlimab follow-up times were matched for each patient.

Results: 66 participants (24 from CARDINAL and 42 from CADENZA), were included in this analysis (Table 1). The median (min, max) follow-up time in each period was 1.8 (0.1, 3.4) years (Table 2). In the PRE-sutimlimab period, the TE incidence rate was 7.5 per 100 patient-years compared to 4.4 ON-sutimlimab (p=0.3056). TE events in the ON-sutimlimab period included cerebral venous sinus thrombosis (CVST) (n=1), device-related thrombosis (n=1), peripheral artery thrombosis (n=1), transient ischemic attack (TIA) (n=1), and deep vein thrombosis (n=1). CVST and peripheral artery thrombosis were reported as serious events, and all other events were reported as nonserious. Only the CVST was assessed as related to sutimlimab by the investigator; sutimlimab was temporarily interrupted due to the event. Of the participants that experienced a TE event in the ON-sutimlimab period, 4/5 had a history of TE risk factors and of those, 1 had a confirmed previous TIA.

Conclusion(s): Analysis of matched adjudicated TE events from the CARDINAL and CADENZA studies suggests a trend toward a reduced risk of TE ON-sutimlimab compared to the PRE-sutimlimab period in this medically complex CAD cohort.