Crizanlizumab halved the likelihood of priapic events among patients treated with sickle cell-associated priapism, according to findings from a phase 2 trial.
In new data from the SPARTAN trial presented last week at the American Society of Hematology (ASH) 2022 Meeting in New Orleans, a team of US researchers found that the monoclonal antibody was associated with a reduction in priapic episodes at half a year. treatment
Presented by Dr. Alan Anderson of the Prisma Health-Upstate Comprehensive Sickle Cell Disease Program at the University of South Carolina School of Medicine, researchers conducted an interim analysis of SPARTAN, the efficacy and safety of crizanlizumab in patients with sickle cell disease. from priapism—a painful penile erection that occurs in more than one-third of adult men with sickle cell disease.
As Anderson and colleagues noted, priapism may occur from the underlying mechanism of microcapillary vascular occlusion in these paitnets.
“To date, there are no drugs proven to treat priapism that modify sickle cell disease,” they wrote. “Crizanlizumab is a monoclonal antibody that binds and blocks P-selectin; an essential mechanical component of the forest-occlusive process. Based on the results of the SUSTAIN trial, crizanlizumab was approved by the US Food and Drug Administration to reduce the frequency of vaso-occlusive seizures in sickle cell disease patients aged 16 years and older.
The SPARTAN trial population included patients ≥ 12 years of age with any sickle cell genotype. Patients had ≥4 priapic episodes of ≥60 minutes in the 14 weeks prior to the clinical trial. Patients also had to experience ≥3 priapic events during the 12-week screening period and ≥1 event in the 4 weeks prior to treatment initiation.
Patients recorded priapic events via electronic self-report and outcome survey over 26 weeks, including details of start and end dates, sleep status, duration, nonpharmacological treatments, triggers, emergency room visits, and pain intensity.
Investigators treated patients with an infusion of 5.0 mg/kg crizanlizumab in weeks 1 and 3, then every 4 weeks. The primary end point of the analysis was the percent reduction from baseline in the frequency of priapic events over 26 weeks.
At the end of the March 8, 2022 interim analysis, investigators evaluated 24 patients receiving ≥1 dose of crizanlizumab and 3 patients who each missed an infusion. About 70% of the patients were between 18-40 years old; the average age was 29.5 years. All patients were African American. The most common genotype was HbSS (79.2%), and most patients (58.3%) received hydroxyurea therapy before enrollment. About 95% of patients reported pain associated with priapism.
The baseline number of priapic events at week 26 was 51 per patient. After 26 weeks of treatment, the researchers observed a reduction in priapic events in 17 of 24 patients (70.8%). Patients reported a mean reduction in events of 53.1% (95% CI, -73.4 to 9.3). Periods of 15-26 weeks were associated with a higher median baseline percentage (-72.7%; 95% CI, -94.0 to -37.1) than 0-12 weeks (-25.0%; 95% CI, -52, 9 to 1.5). ).
By subgroup analysis, patients with ≥22 baseline events had the greatest event reduction benefit (−62.2%; 95% CI, −76.3 to −17.6). Crizanlizumab was associated with good tolerability; the 2 most common treatment-emergent adverse events were headache (16.7%) and fatigue (12.5%).
Anderson and colleagues concluded that priapism associated with sickle cell disease was roughly halved among patients treated with crizanlizumab over 26 weeks.
“There was a trend toward improved efficacy with longer treatment duration and in patients with a higher number of events at baseline,” they wrote. “The final results of the SPARTAN trial will provide more definitive conclusions about the effectiveness of crizanlizumab in reducing priapism.”
A study titled “SPARTAN,” “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.