The anti-P-selectin monoclonal antibody, crizanlizumab, reduced the annualized rate of vaso-occlusive crises (VOCs) and was well-tolerated among patients with sickle cell disease (SCD), according to interim results of an ongoing phase 2 study published in Blood Advances.
Crizanlizumab is approved by the U.S. Food and Drug Administration to reduce the frequency or to prevent recurrent VOCs among patients with SCD who are age 16 years or older. This approval was based on the results from the SUSTAINE trial. This study evaluated the long-term pharmacokinetics (PK), pharmacodynamics (PD), safety and efficacy of crizanlizumab among adults with SCD.
The open-label, phase 2 SOLACE-adults study (ClinicalTrials.gov Identifier: NCT03264989) treated 57 patients with SCD and a history of VOCs with 5.0 or 7.5 mg/kg of crizanlizumab every 4 weeks for a median duration of 104.7 and 85.7 weeks, respectively. The primary objective of the study was to evaluate the PK and PD, and the secondary objective was to evaluate efficacy and safety.
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At baseline, the median age was 25 and 53% of patients were female. The most common genotypes were HbSS and HbSC. Concomitant hydroxycarbamide or hydroxyurea was taken by 73% and 58% of patients in the 5.0 and 7.5 mg/kg groups, respectively. There were 42% and 25% of patients in the 5.0 and 7.5 mg/kg groups, respectively, who had experienced 5 or more VOCs in the previous 12 months, the majority of which were uncomplicated.
Crizanlizumab decreased the annualized rate of VOCs that led to a health care visit with a median absolute reduction from baseline of -0.88 with the 5.0 mg/kg dose and -0.93 with the 7.5 mg/kg dose. The baseline rates were 4.0 and 2.0 in the 5.0 and 7.5 mg/kg groups, respectively, which decreased to 2.25 and 2.0. Freedom from VOC was achieved by 20.0% of patients in the 5.0 mg/kg group and 41.7% of patients in the 7.5 mg/kg group during the first 12 months of treatment.
The serum levels of crizanlizumab reached near maximum levels by the end of its infusion and began to decrease after 6 hours.
There was 1 treatment-related grade 3 adverse event (AE) in the 7.5 mg/kg group and no treatment-related serious AEs. There was 1 patient who experienced a grade 2 infusion-related reaction that resolved without treatment withdrawal. There were no treatment-related bleeding events or infections.
The authors concluded that the results from this study demonstrate “the potential sustained efficacy and long-term safety of the drug after >12 months treatment.”
Disclosures: This study was supported by Novartis. Please see the original reference for a full list of disclosures.
Reference
Kanter J, Brown C, Norris C, et al. Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease. Blood Adv. 2023;7:943-952. doi: 10.1182/bloodadvances.2022008209
