Safety profile of crizanlizumab 5.0 mg/kg in sickle cell disease: pooled data from clinical trials

Objectives This pooled analysis evaluated key safety endpoints in patients with sickle cell disease treated with crizanlizumab. Methods Two clinical data pools were created: Pool 1 (crizanlizumab group from three Phase 2 [SUSTAIN, SOLACE-adults, and SOLACE-Kids] and one Phase 3 study [STAND]) and Pool 2 comprising only placebo-controlled trials (crizanlizumab and placebo group from SUSTAIN and STAND). Adverse events (AEs), treatment-related AEs (TRAEs), discontinuations due to AEs and deaths were evaluated. SAS v.9.4 was used for all analyses. Results Overall, 245 patients in Pool 1 and 150 in Pool 2 received crizanlizumab and 147 in Pool 2 received placebo. The median crizanlizumab exposure was 87.4 and 54.1 weeks in Pool 1 and 2. Headache and pyrexia were common AEs across groups. Infection-related events were reported in 62.4%, 56.7%, and 55.1% of patients, infusion-related reactions were reported in 38.8%, 36.7%, and 27.9% of patients and bleeding-related events occurred in 16.7%, 14.0%, and 10.2% of patients in Pool 1, Pool 2 crizanlizumab, and Pool 2 placebo, respectively. TRAEs were reported in 31.8%, 34.7%, and 24.5% of patients in Pool 1, Pool 2 crizanlizumab, and Pool 2 placebo, respectively. Discontinuations due to AEs were low in Pool 1 (3.3%), Pool 2 crizanlizumab (2.7%), and Pool 2 placebo (3.4%). On-treatment deaths were seen in five (2%) patients in Pool 1 and three (2%) each in Pool 2 crizanlizumab and placebo groups. Conclusions Crizanlizumab was well tolerated, with an acceptable safety profile. Most AEs were mild to moderate, and discontinuations due to AEs were infrequent.