Long-term safety profile of sutimlimab in adult Japanese patients with cold agglutinin disease

Abstract

Sutimlimab, a complement inhibitor, has recently been approved in Japan for treating cold agglutinin disease (CAD). We report the safety and efficacy of sutimlimab in Japanese patients with CAD who completed a global phase 3 clinical trial (CARDINAL/CADENZA: 26-week treatment with 1-2 years of open-label extension [OLE] periods) and subsequently participated in the Japanese OLE study. Patients with a recent history of blood transfusion (CARDINAL, n = 3) and those without (CADENZA, n = 4) were analyzed (71.4% female; median [range] baseline age: 70 [46-83] years). For CARDINAL/CADENZA, the treatment duration (median [range]) was 140.9 (104.9-157.3) weeks, and the cessation period was 70 (61-133) weeks. For the Japanese OLE study, the treatment duration was 47.1 (15.1-49.1) weeks. Three (42.9%) patients experienced treatment-related and treatment-emergent adverse events (TEAEs): injection site erythema, cystitis bacterial, viral infection, and blood pressure increased during CARDINAL/CADENZA. One (14.3%) patient experienced one treatment-related TEAE (urinary tract infection) during the Japanese OLE study. One patient died of renal failure, considered unrelated to sutimlimab, that was exacerbated by hepatorenal syndrome due to liver cirrhosis and bacterial peritonitis, in addition to CKD. Hemoglobin and bilirubin levels improved during treatment but deteriorated after withdrawal and recovered on retreatment. Sutimlimab was well tolerated over a median of 3.8 years, with no new safety concerns identified during retreatment.

Keywords: Cold agglutinin disease; Complement inhibitor; Hemolytic anemia; Long-term; Sutimlimab.

Fig. 1

Study design. a Of the seven patients who participated in the Japan OLE study, one patient was assigned to placebo group in the CADENZA study during the 26-week treatment period (Part A). The study drug was administered on Day 0, Day 7, and subsequently every 2 weeks. b OLE phase (Part B) was 2 years in the CARDINAL study and 1 year in the CADENZA study after the last patient completed Part A, followed by a 9-week safety follow-up period. All patients received sutimlimab every 2 weeks. c Patients to receive sutimlimab until it is commercially available or discontinuation of study drug in the Japan OLE study. d The data were collected up to 2 weeks after the last (available) dose. BL baseline, EOS end of study, OLE open-label extension

Fig. 2

Box–whisker plot for serum hemoglobin levels at each time point. The upper and lower limits of the box plot denote interquartile ranges; whiskers denote maximum and minimum ranges. The line and X in the box plot denote median and mean, respectively. The circle denotes outlier. The number below each timepoint denotes median (range) of the hemoglobin levels (N = 7). EOS, end of study; OLE, open-label extension

Fig. 3

Box–whisker plot for serum bilirubin levels at each time point. The upper and lower limits of the box plot denote inter-quartile ranges, whiskers denote maximum and minimum ranges. The line and X in the box plot denote median and mean, respectively. The number below each timepoint denotes median (range) of the bilirubin levels (N = 7). EOS, end of study; OLE, open-label extension