Treatment with the investigational drug crizanlizumab (SEG101) reduced pain in patients with sickle cell disease (SCD) who were experiencing vaso-occlusive crisis according to posthoc results of the phase II SUSTAIN study published online in The American Journal of Hematology. The study found that more than twice as many patients with SCD treated with crizanlizumab did not experience a VOC compared with those treated with placebo.
Treatment with the investigational drug crizanlizumab (SEG101) reduced pain in patients with sickle cell disease (SCD) who were experiencing vaso-occlusive crisis (VOC), according to posthoc results of the phase II SUSTAIN study, published online in The American Journal of Hematology.1 The study found that more than twice as many patients with SCD treated with crizanlizumab did not experience a VOC compared with those treated with placebo (35.8% vs 16.9%).
Crizanlizumab was shown to prevent VOCs in patients with 2 to 4 events in the year leading up to the study initiation. The drug prevented VOC events for 17 of 42 patients in the treated arm of the study and also prevented VOCs in patients with between 5 and 10 events in the year leading up to the study intervention, working for 7 of 25 patients in the treatment group and only 1 of 24 in the placebo group.
Crizanlizumab binds with P-selectin on the surface of endothelial cells and platelets in blood vessels, causing a blockage of P-selectin, which is one of the major drivers of the vaso-occlusive process. Novartis, the developer, expects to file a New Drug Application for the drug with the FDA in 2019.
VOC is the most common and painful complication among patients with SCD, and the main reason for these patients to be hospitalized for treatment. VOCs, which are triggered by multicell adhesion, are also associated with increased morbidity and mortality and can result in stroke, organ damage, or failure. There are few treatment options for VOC to date.
The SUSTAIN trial was a multicenter, multinational, randomized, placebo-controlled, double-blind 12-month study to assess safety and efficacy of crizanlizumab, with or without the concomitant use of hydroxyurea therapy in patients with SCD who have sickle-cell related pain crises. The primary results of SUSTAIN were published in The New England Journal of Medicine2 in 2017 and showed that crizanlizumab reduced the median annual rate of sickle cell pain crises by 45.4% compared with placebo (1.64 vs 2.98; P = .10) in patients with or without hydroxyurea therapy.
In the current posthoc analysis of the SUSTAIN study data, researchers analyzed data from 132 patients to determine the annual rate of VOC in patients who were treated with crizanlizumab compared with placebo. A total of 67 patients received crizanlizumab (5 mg/kg) and 65 received placebo. Each patient enrolled in the study had experienced at least 2 VOCs in the 12 months prior to study initiation. A total of 83 patients experienced between 2 and 4 VOC events, and 49 experienced between 5 and 10 VOCs. Most patients in the study (71.2%) had homozygous hemoglobin S subtype (HbSS) of disease, the most common SCD type. These patients were evenly split among the study cohorts. The remaining study subjects were classified as non-HbSS patients.
No new safety concerns emerged from the analysis; adverse events attributable to treatment were similar between the crizanlizumab and placebo arms across all subgroups. Adverse events that occurred in 10% or more patients in either the active treatment group or at a frequency that was at least twice as high as that in the placebo group were arthralgia, diarrhea, pruritis, vomiting, and chest pain. There were no apparent increases in infections with crizanlizumab treatment.
The study’s findings suggest that if approved by the FDA, crizanlizumab may become an important new therapeutic option for SCD. The investigators said they were encouraged that results from this analysis of SUSTAIN study data found that crizanlizumab could substantially delay or prevent these crises, which may also mean less organ damage in the long run.