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

Introduction 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. Here, we assess the TE events PRE- and ON-sutimlimab treatment from the Phase 3 CARDINAL (NCT03347396) and CADENZA (NCT03347422) studies.

Method 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 ([Fig. 1]). The median (min, max) follow-up time in each period was 1.8 (0.1, 3.4) years ( [Fig. 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.

Fig. 1  Summary of Baseline Characteristics of Patients That Met the Inclusion Criteria for the Post-hoc Analysis by Matcheda Thromboembolic (TE) Events After Treatment in the CARDINAL and CADENZA Studies

Fig. 2  Summary of Matched^a Adjudicated Thromboembolic (TE) Events for CARDINAL and CADENZA Studies

Conclusion 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.

 

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Conflict of Interest

AR has received honoraria from and participated in a data safety monitoring board or advisory board for Alexion, Amgen, Apellis, Novartis, Roche, Sanofi, and Sobi; partook in a data safety monitoring board or advisory board for Bioverativ; and has had support provided for meetings from Sobi. YU has received research support from Chugai Pharma, consultancy fees from Alexion, Asahi Kasei, Chugai Pharma, Incyte, Novartis, Sanofi and Sobi, and Janssen Pharmaceutical, honoraria from Alexion, Novartis and Sanofi, participation in an advisory board from Novartis and has a membership on an entity’s board of directors or advisory committees from Sanofi and Sobi. KM has participated in data and safety monitoring boards for Argenex and Principia, and consulted/participated in advisory boards for Sanofi and Novartis. CMB has received grants from Alexion, Argenx, Incyte, and Rigel; honoraria from Alexion, Argenx, Novartis; and Sanofi; and partook in a data safety monitoring board or advisory board for Alexion, Argenx, Incyte, Novartis, and Sanofi. UK, KK, MW, FS, and RY are employees of Sanofi and may hold stock options in the company. This work and the CADENZA and CARDINAL studies were funded by Sanofi.

Publication History

Article published online:
26 February 2024