SUSTAIN study shows crizanlizumab increased the number of patients free of sickle cell pain crises vs placebo - Novartis

Results from a post hoc analysis of the Phase II SUSTAIN study of crizanlizumab, a humanized anti-P-selectin monoclonal antibody being investigated for the treatment of sickle cell disease (SCD), have been published in the American Journal of Hematology. The analysis showed that more patients treated with crizanlizumab did not experience a vaso-occlusive crisis (VOC) vs those treated with placebo (35.8% vs 16.9%), specifically patients with a history of 2-10 VOCs in the previous year.

VOCs are a painful complication of SCD and the main reason why patients seek medical care in hospitals. VOCs, which are triggered by multi-cell adhesion, are associated with increased morbidity and mortality, and can result in stroke, as well as organ damage or failure. Currently, treatment options for VOCs are limited.

The post hoc analysis reviewed 52-week results from 132 patients, including 67 treated with crizanlizumab 5 mg/kg and 65 who received placebo. All evaluated patients had a history of at least 2 VOCs in the year prior to the study, with 62.9% (n=83) having experienced 2-4 events and 37.1% (n=49) with 5-10 events. The most common genotype in SCD, homozygous hemoglobin S (HbSS), was identified in most SUSTAIN patients (n=94; 71.2%), and patients with this genotype were evenly distributed between study arms. The analysis found that treatment with crizanlizumab may prevent VOCs, both in patients who had 2-4 and 5-10 disease-related pain events in the year prior to the study, as well as those with HbSS. Of the subgroups evaluated, a considerable number of patients across multiple subgroups treated with crizanlizumab did not experience a VOC compared with those treated with placebo, including: Those with 2-4 events in the year prior to participating in the study (17 out of 42 patients or 40.5% vs 10 out of 41 patients, or 24.4%). Those with 5-10 events in the year prior to participating in the study (7 out of 25 patients or 28.0% vs 1 out of 24 patients, or 4.2%). Those with the HbSS genotype (15 out of 47 patients or 31.9% vs 8 out of 47 patients, or 17.0%). Those also with concomitant use of hydroxyurea (14 out of 42 patients 33.3% vs 7 out of 40 patients, or 17.5%). No new safety concerns emerged in the post hoc analysis as adverse events attributed to treatment were similar between the crizanlizumab and placebo arms across all subgroups. Adverse events that occurred in 10% or more of the patients in either active-treatment group (2.5 mg/kg; 5 mg/kg) and at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritus, vomiting, and chest pain. There were no apparent increases in infections with crizanlizumab treatment.

See- "Effect of crizanlizumab on pain crises in subgroups of patients with sickle cell disease: A SUSTAIN study analysis"-Abdullah Kutlar MD Julie Kanter MD Darla K Liles MD Ofelia A Alvarez MD Rodolfo D Can�ado MD Jo�o R Friedrisch MD Jennifer M Knight?Madden PhD Andreas Bruederle MD � First published: 08 October 2018 https://doi.org/10.1002/ajh.25308.