Crizanlizumab was associated with a halved likelihood of priapic events in treated patients with sickle-cell priapism, according to results from a phase 2 trial.
In new data from the SPARTAN trial presented at the 2022 American Society of Hematology (ASH) annual meeting in New Orleans last week, a team of American researchers observed that the monoclonal antibody was associated with a reduction in priapic episodes over one semester of treatment.
Presented by Alan Anderson, MD, of the Prisma Health-Upstate Comprehensive Sickle Cell Disease Program at the University of South Carolina School of Medicine, investigators performed an interim analysis of SPARTAN to assess the efficacy and safety of crizanlizumab in patients with sickle cell disease suffering from priapism – a painful penile erection that occurs in more than a third of adult men with sickle cell disease.
As noted by Anderson and colleagues, priapism may arise from the underlying mechanism of microcapillary vaso-occlusion in these paitnets.
“To date, there are no effective sickle-cell modifying drugs to treat priapism,” they wrote. “Crizanlizumab is a monoclonal antibody that binds and blocks P-selectin; a key mechanistic component of the vaso-occlusive process. Based on the results of the SUSTAIN trial, crizanlizumab has been approved by the United States Food and Drug Administration to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease aged 16 and older.
The SPARTAN trial population included patients ≥ 12 years of age with any sickle cell genotype. Eligible patients had experienced ≥ 4 priapic episodes of ≥ 60 minutes in the 14 weeks prior to the clinical trial. Patients were additionally required to experience ≥ 3 priapic events during the 12-week screening period and ≥ 1 event within 4 weeks prior to treatment initiation.
Patients recorded priapic events via electronic self-reports and 26-week outcome surveys, including details of onset and end date, sleep status, duration, non-pharmacological treatments, triggers, emergency room visits and pain intensity.
Investigators treated patients with 5.0 mg/kg crizanlizumab by intravenous infusion at weeks 1 and 3, then every 4 weeks thereafter. The primary endpoint of the analysis was percent reduction from baseline in the frequency of priapic events over 26 weeks.
As of the interim analysis deadline of March 8, 2022, investigators had evaluated 24 patients receiving ≥ 1 dose of crizanlizumab, and 3 patients who had each missed 1 infusion. About 70% of patients were between 18 and 40 years old; the median age was 29.5 years. All patients were African American. The most common genotype was HbSS (79.2%) and the majority of patients (58.3%) had received hydroxyurea therapy prior to enrolment. About 95% of patients reported pain associated with priapism.
The median baseline number of priapic events per 26 weeks was 51 per patient. After 26 weeks of treatment, investigators observed a reduction in priapic events in 17 of 24 patients (70.8%). Patients reported a median 53.1% reduction in events (95% CI, -73.4 to 9.3). Weeks 15 to 26 was associated with a greater median percentage reduction from baseline (-72.7%; 95% CI, -94.0 to -37.1) than weeks 0 to 12 ( -25.0%; 95% CI, -52.9 to 1.5).
By subgroup analyses, patients with ≥ 22 baseline events experienced the greatest benefit in event reduction (-62.2%; 95% CI, -76.3 to -17.6). Crizanlizumab was associated with good tolerance; the 2 most common treatment-related adverse events included headache (16.7%) and fatigue (12.5%).
Anderson and colleagues concluded that sickle cell priapism was approximately halved in affected patients treated with crizanlizumab for 26 weeks.
“There was a trend for improved efficacy with a longer treatment period and in patients with a higher number of events at baseline,” they wrote. “The final results from the SPARTAN trial will provide more definitive conclusions regarding the efficacy of crizanlizumab in decreasing priapism.”
The study, “Interim Analysis of a Phase 2 Trial to Assess the Efficacy and Safety of Crizanlizumab in Sickle Cell Disease Patients with Priapism (SPARTAN),” was presented at ASH 2022.
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