S268: interim analysis of a phase 2 trial to assess the efficacy and safety of crizanlizumab in sickle cell disease patients with priapism (spartan)

Background: Priapism, a painful, sustained penile erection, occurs due to microcapillary vaso-occlusion in approximately 35% of adult males with sickle cell disease (SCD). There is no effective SCD-modifying drug proven to treat priapism. Crizanlizumab binds and blocks a key mechanistic component of the vaso-occlusive process, P-selectin. 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 crises in SCD patients aged ≥16 years. Aims: In this interim analysis of the SPARTAN trial (NCT03938454), we evaluate the efficacy and safety of crizanlizumab in SCD patients with priapism. Methods: The trial included SCD patients (all genotypes) aged ≥12 years with ≥4 priapic episodes lasting ≥60 minutes over the 14 weeks prescreening period and experiencing ≥3 priapic events during the 12-week screening period with ≥1 event occurring within 4 weeks prior to the first treatment. Priapic events were documented through electronic self-reporting tools and validated patient-reported outcomes surveys for 26 weeks. Patients received crizanlizumab 5.0-mg/kg intravenous infusion at week 1, week 3, and every 4 weeks thereafter. The primary endpoint was the percent reduction from baseline in the frequency of priapic events by 26 weeks. Results: At the interim analysis (data cut-off, March 8, 2022), 24 patients had received ≥1 dose of crizanlizumab and 3 patients missed 1 infusion each. Most patients (70.8%) were between the ages of 18 and 40 years, and the median (range) age was 29.5 (17-58) years. All patients were African American, 79.2% had HbSS genotype and 58.3% reported receiving hydroxyurea prior to enrollment. The first episode of priapism occurred between the ages of 13 and 25 years in 79.2% of the patients. The frequency and length of priapic events varied with no specific pattern; however, most patients (95.8%) reported priapism-associated pain. Common nonpharmacological methods that helped during priapism were shower/bath (58.3%) and exercise (58.3%). The most common patient-reported emotions during study initiation were exhaustion (50%), frustration (45.8%), embarrassment (41.7%) and anxiousness (41.7%). The median (IQR) baseline number of priapic events adjusted for 26 weeks per patient was 51 (11-74). By week 26, a reduction in priapic events occurred in 70.8% (17/24) patients. The median (IQR) percent reduction from baseline in priapic events per patient was −53.1% (−73.4% to 9.3%). There was a higher median (IQR) percent reduction from baseline during weeks 15 to 26 (−72.7% [−94.0% to −37.1%]) versus weeks 0 to 12 (−25.0% [−52.9% to 1.5%]). In a subgroup analysis by frequency of baseline priapic events, the largest benefit was observed in patients with ≥22 baseline events (median [IQR], −62.2% [−76.3% to −17.6%]). Results for each patient are presented in the Figure. Crizanlizumab was well tolerated with the 2 most frequent treatment-emergent adverse events (TEAEs) being headache (16.7%) and fatigue (12.5%). No patients discontinued crizanlizumab prematurely. Summary/Conclusion: Patients with SCD-related priapism treated with crizanlizumab over 26 weeks experienced approximately half as many priapic events compared with baseline. There was a trend toward improved efficacy with a longer treatment period and in patients with a higher number of events at baseline. Crizanlizumab was safe and well tolerated with observed TEAEs consistent with the reported safety profile. The final results of the SPARTAN trial will provide more definitive conclusions on the efficacy of crizanlizumab in reducing priapism. Figure:Keywords: Vasoocclusive crisis, Sickle cell patient, P-selectin, Sickle cell disease