Advancements in Sickle Cell Disease Treatment: A Review of Crizanlizumab
DOI:
https://doi.org/10.56570/zygtya82Keywords:
Sickle Cell Disease (SCD), Crizanlizumab, Vaso-occlusive crises (VOCs), P-selectin, Endothelial adhesion, Targeted therapy, Monoclonal antibody, Clinical trials, Safety profile, Voxelotor, L-glutamine, Novel therapeutics, Disease management, Quality of lifeAbstract
Sickle cell disease (SCD) is a chronic, inherited blood disorder marked by the presence of abnormal hemoglobin, which causes red blood cells to assume a rigid, sickle-like shape. These distorted cells contribute to hemolysis, impaired blood flow, and recurrent vaso-occlusive crises (VOCs), the hallmark and most debilitating complication of the disease. Beyond acute pain episodes, Sickle cell disease leads to progressive organ damage and reduced life expectancy, placing a substantial burden on patients and healthcare systems worldwide. While supportive care has long been the cornerstone of management, the emergence of targeted therapies offers new hope. Crizanlizumab, a humanized monoclonal antibody directed against P-selectin, disrupts the cellular adhesion processes that drive vaso-occlusive crises. This review highlights the pathophysiology of Sickle cell disease, details the mechanism of action of crizanlizumab, and evaluates clinical trial evidence regarding its efficacy, safety, and therapeutic potential. Collectively, the findings underscore crizanlizumab’s promise as a transformative therapy that can reduce VOC frequency and improve quality of life for individuals living with SCD.References
Kavanagh PL, Fasipe TA, Wun T. Sickle cell disease: a review. JAMA. 2022;328(1):57-68. 2. GBD 2021 Sickle Cell Disease Collaborators. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021. Lancet Haematol. 2023;10(8):e585-e599.
Mayo-Gamble TL, Schlundt D, Cunningham-Erves J, et al. Sickle cell carriers’ unmet information needs: beyond knowing trait status. J Genet Couns. 2019;28(4):812-821.
Elendu C, Amaechi DC, Alakwe-Ojimba CE, et al. Understanding sickle cell disease: causes, symptoms, and treatment options. Medicine (Baltimore). 2023;102:e35237.
Jang T, Poplawska M, Cimpeanu E, Mo G, Dutta D, Lim SH. Vaso-occlusive crisis in sickle cell disease: a vicious cycle of secondary events. J Transl Med. 2021;19:397.
Zadeh FJ, Fateh A, Saffari H, et al. The vaso-occlusive pain crisis in sickle cell patients: a focus on pathogenesis. Curr Res Transl Med. 2025;73:103512.
López Rubio M, Argüello Marina M. The current role of hydroxyurea in the treatment of sickle cell anemia. J Clin Med. 2024;13.
Gardner RV. Crizanlizumab in vaso-occlusive crisis caused by sickle cell disease. Drugs Today (Barc). 2020;56(11):705-714.
DeBonnett L, Joshi V, Silva-Pinto AC, et al. Real-world evidence of crizanlizumab showing reductions in vaso-occlusive crises and opioid usage in sickle cell disease. Eur J Haematol. 2025;114:293-302.
Sundd P, Gladwin MT, Novelli EM. Pathophysiology of sickle cell disease. Annu Rev Pathol. 2019;14:263-292.
Kaur K, Kennedy K, Liles D. Crizanlizumab in sickle cell disease. Pain Manag. 2023;13(—):—. (No page numbers available in your document.)
Karki NR, Kutlar A. P-selectin blockade in the treatment of painful vaso-occlusive crises in sickle cell disease: a spotlight on crizanlizumab. J Pain Res. 2021;14:849-856.
Ataga KI, Kutlar A, Kanter J, et al. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017;376:429-439.
Yassin M, Minniti C, Shah N, et al. Evidence and gaps in clinical outcomes of novel pharmacologic therapies for sickle cell disease: a systematic literature review. Blood Rev. 2025;73:101298.
Kanter J, Mennito S, Nair SM, et al. Pharmacokinetics, pharmacodynamics, safety, and efficacy of crizanlizumab in patients with sickle cell disease: final results from the phase II SOLACE-Adults study. Ther Adv Hematol. 2024;15:20406207241292508.
Heeney M, Rees D, de Montalembert M, et al. Safety and efficacy of crizanlizumab in adolescents with sickle cell disease: initial data from the phase II, multicenter, open-label SOLACE-Kids trial. Hemasphere. 2022;6(suppl):12.
Karkoska K, Jacob SA, McGann PT. Accelerated drug approvals and patient trust: impact of voxelotor and crizanlizumab for sickle cell disease. Blood Adv. 2025;9:2857-2862.
Abboud MR, Cançado RD, De Montalembert M, et al. Crizanlizumab with or without hydroxyurea in patients with sickle cell disease (STAND): primary analyses from a placebo-controlled, randomised, double-blind, phase 3 trial. Lancet Haematol. 2025;12:e248-e257.
Niihara Y, Miller ST, Kanter J, et al. A phase 3 trial of L-glutamine in sickle cell disease. N Engl J Med. 2018;379:226-235.
Kutlar A, Joshi V, Brueckner A, et al. Safety profile of crizanlizumab 5.0 mg/kg in sickle cell disease: pooled data from clinical trials. Blood. 2023;142:1139.