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. Clinical trial registration information NCT01895361, NCT03264989, NCT03474965, NCT03814746; ClinicalTrials.gov