Introduction: Priapism is a painful, sustained penile erection that occurs in 35% of adult men with sickle cell disease (SCD) and may result from the underlying mechanism of vaso-occlusion. To date, there is no effective disease-modifying drug proven to treat priapism. Crizanlizumab is a monoclonal antibody that binds and blocks P-selectin, a key mechanistic component of vascular endothelial adhesion. Based on the results of the SUSTAIN trial, crizanlizumab was approved by the FDA to reduce the frequency of vaso-occlusive crises in patients with SCD aged ≥16 years. In this primary analysis of the Phase 2 SPARTAN trial (NCT03938454), we evaluated the efficacy and safety of crizanlizumab after 26 weeks of treatment in patients with SCD-related priapism.

Methods: The SPARTAN trial included male patients aged ≥12 years with all SCD genotypes who experienced ≥4 priapic episodes lasting ≥60 min over the 14-week period preceding screening. Eligible patients also experienced ≥3 priapic episodes during the subsequent 12-week screening period with ≥1 event occurring within 4 weeks prior to the first treatment. After enrollment priapic events were documented through electronic self-reporting tools and validated patient-reported outcomes surveys for 26 weeks and included start/end date, sleep status, duration, non-pharmacological treatment, triggers, emergency department visit, and pain intensity during the screening period. Baseline priapic events were collected for each patient during the 12-week screening period. Patients received crizanlizumab 5.0 mg/kg IV infusion on week 1, week 3, and every 4 weeks thereafter. The primary endpoint was percent reduction from adjusted baseline period in priapic events by 26 weeks. Percent reduction from baseline in priapic events was tested using a one-sided Wilcoxon's Sign Rank test. Hodges-Lehmann estimate of median percent reduction in priapic events (with 95% CIs) was also reported.

Results: Data cutoff was March 28, 2023. Of the 36 patients enrolled, 26 (72.2%) were between 18 and 40 years, and the median (range) age was 29 (14-58) years. Most patients were HbSS genotype (n=29, [80.6%]) and more than half were on hydroxyurea (n=21, [58.3%]). Patient-reported history prior to crizanlizumab treatment revealed that more than half of patients experienced priapism daily or every other day (n=21, [58.3%]) and most reported a duration of 1 to 5 h (n=33, [91.7%]). The most common patient-reported emotions at the start of the study were frustration and exhaustion, reported by ≈50% of patients. The median (IQR) baseline number of priapic events adjusted for 26 weeks per patient was 42 (13-73) events ( Table). All patients experienced events lasting 1 to ≤4 h, although some also experienced severe events lasting >4 to 6 h (n=19, [52.8%]) and >6 to ≤12 h (n=11, [30.6%]). In one case, 38 days of screening period baseline data was not reported, resulting in a strong outlier that affected the results ( Patient 1, Figure). Thirty-six patients received ≥1 dose of crizanlizumab, with a median cumulative dose of 35.0 mg/kg over 26 weeks; 5 patients each missed 1 infusion and 1 patient missed 2 infusions. The Hodges-Lehmann estimate of median percent reduction from baseline in priapic events per patient was 46.0% (95% CI: 23.5%-65.4%; P=.068). Twenty-eight patients (77.8%) reported a reduction from baseline in priapic events ( Figure). A subgroup analysis revealed a trend towards a larger percent reduction in events for patients with ≥22 baseline events, possibly indicating that patients with severe disease benefitted more from treatment. The most frequent treatment-emergent adverse event (TEAE) was headache (16.7%). No patients discontinued crizanlizumab prematurely and only one patient withdrew consent by week 26.

Conclusions: Primary analyses from the SPARTAN trial showed that 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 towards a more significant reduction in frequency of episodes in patients with severe disease. Crizanlizumab was safe and well tolerated, with observed TEAEs consistent with the safety profile seen in other clinical trials. Final analyses of the SPARTAN trial will provide data over 52 weeks and may provide further support for the role of crizanlizumab in reducing frequency of priapic events.

Idowu:Novo Nordisk: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Bluebird Bio: Consultancy; Vertex: Consultancy; Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion: Research Funding; Pfizer: Consultancy, Research Funding, Speakers Bureau; Forma Therapeutics: Research Funding; Agios Pharmaceuticals, Inc.: Research Funding. DeBaun:Vertex/CRISPR: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Other: Study steering committee member; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; FORMA: Consultancy. Burnett:Novartis Pharmaceuticals Corporation: Other: Study Steering Committee member. Darbari:Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics (Pfizer): Membership on an entity's Board of Directors or advisory committees. Adam:Novartis Pharmaceuticals Corporation: Research Funding. Anderson:Pfizer: Consultancy, Research Funding, Speakers Bureau; Vertex: Consultancy; Novartis Pharmaceuticals Corporation: Consultancy; Novo Nordisk: Consultancy. Kanter:National Alliance of Sickle Cell Centers: Other: President; Watkins, Lourie, Roll & Chance: Consultancy; Vertex: Consultancy; Guidepoint Global: Honoraria; CDC: Research Funding; Chiesi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bausch: Consultancy; Austin Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; HRSA: Research Funding; Bluebird Bio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; ECOR-1: Consultancy; Fulcurm: Consultancy; Glycomimetics: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; BEAM: Consultancy, Research Funding; NHLBI: Research Funding. Billett:Novartis: Research Funding; Global Blood Therapeutics/Pfizer: Other: Clinical trial activity, Research Funding. Liles:Abbvie: Other: Clinical trial activity (Principal investigator or sub-investigator); Alpine Immune Sciences: Other: Clinical trial activity (Principal investigator or sub-investigator); Annexon Biosciences: Other: Clinical trial activity (Principal investigator or sub-investigator); Astex Pharmaceuticals: Other: Clinical trial activity (Principal investigator or sub-investigator); Baxalta: Other: Clinical trial activity (Principal investigator or sub-investigator); BeiGene: Other: Clinical trial activity (Principal investigator or sub-investigator); Bioverativ: Other: Clinical trial activity (Principal investigator or sub-investigator); CSL Behring: Other: Clinical trial activity (Principal investigator or sub-investigator); Celgene: Other: Clinical trial activity (Principal investigator or sub-investigator); Delta-Fly Pharma: Other: Clinical trial activity (Principal investigator or sub-investigator); Exact Sciences: Other: Clinical trial activity (Principal investigator or sub-investigator); Forma Therapeutics: Other: Clinical trial activity (Principal investigator or sub-investigator); Global Blood Therapeutics: Other: Clinical trial activity (Principal investigator or sub-investigator); Immunovant: Other: Clinical trial activity (Principal investigator or sub-investigator); Incyte: Other: Clinical trial activity (Principal investigator or sub-investigator); Janssen Pharmaceuticals: Other: Clinical trial activity (Principal investigator or sub-investigator); NeoImmuneTech: Other: Clinical trial activity (Principal investigator or sub-investigator); Novartis: Other: Clinical trial activity (Principal investigator or sub-investigator); Novo Nordisk: Other: Clinical trial activity (Principal investigator or sub-investigator); Partner Therapeutics: Other: Clinical trial activity (Principal investigator or sub-investigator); Pharm-Olam: Other: Clinical trial activity (Principal investigator or sub-investigator); Principia Biopharma: Other: Clinical trial activity (Principal investigator or sub-investigator); Salix Pharmaceuticals: Other: Clinical trial activity (Principal investigator or sub-investigator); Sanofi-Aventis: Other: Clinical trial activity (Principal investigator or sub-investigator); Takeda: Other: Clinical trial activity (Principal investigator or sub-investigator); Vifor Pharma: Other: Clinical trial activity (Principal investigator or sub-investigator). Decastro:Global Blood Therapeutics: Other: Advisory board; Forma Therapeutics: Other: Advisory board; GlycoMimetics: Other: Advisory board; Novartis: Other: Advisory board. Andemariam:Pfizer: Research Funding; NovoNordisk: Consultancy; GSK: Consultancy; Global Blood Therapeutics: Consultancy, Research Funding; Accordant: Consultancy; Hemanext: Consultancy, Research Funding; Forma Therapeutics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; HRSA: Research Funding; PCORI: Research Funding; Sanofi Genzyme: Consultancy; Emmaus: Consultancy; Connecticut Department of Public Health: Research Funding; Bluebird: Consultancy; American Society of Hematology: Research Funding; Agios: Consultancy; Afimmune: Consultancy; Vertex: Consultancy. Heeney:Novartis, FORMA Therapeutics, Global Blood Therapeutics, Oric Pharma and Bluebird Bio and Pharmacosmos, Weatherden, Blueprint Medicines, Alexion, Bluebird Bio and Pharmacosmos: Consultancy; Novartis: Research Funding; Agios: Other: podcast speaker; Vertex/CRISPR: Other: Membership of a data and safety monitoring board. McLemore:Novartis, Pfizer, NHLBI: Research Funding. Kolekar:Novartis Healthcare Pvt. Ltd.: Current Employment. Laine:Novartis Pharmaceuticals Corporation: Current Employment. Paulose:Novartis Pharmaceuticals Corporation: Current Employment. Sarkar:Novartis Healthcare Pvt. Ltd.: Current Employment. Vignogna:Novartis Pharmaceuticals Corporation: Current Employment. El Rassi:Novartis, Forma Therapeutics, Agios: Research Funding.

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2023
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