Clin Exp Pediatr.  2025 Feb;68(2):106-114. 10.3345/cep.2024.00500.

Promising role of voxelotor in managing sickle cell disease in children: a narrative review

• Agrawal A
• Jadon G
• Singh J
• Janjua D

• KMID: 2564614
• DOI: http://doi.org/10.3345/cep.2024.00500

Abstract

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia and intermittent vasoocclusive crises. To date, 4 disease-modifying drugs have been approved for the treatment of SCD: hydroxyurea (an S-phase inhibitor), L-glutamine (an amino acid), crizanlizumab (a P-selectin inhibitor), and voxelotor (a hemoglobin S polymerization inhibitor). Preclinical studies suggested that voxelotor effectively treats SCD and sickle cell anemia (SCA). In a phase III trial, voxelotor-treated patients showed significantly elevated hemoglobin levels (>1 g/dL from baseline) compared to placebo-treated patients. The group that received voxelotor also showed a greater decrease in hemolytic markers but a comparable incidence of side effects. Six ongoing clinical trials also sought to ascertain the effectiveness and safety of high-dose voxelotor when administered to children younger than 12 years. Studies assessing their long-term efficacy and safety are needed to fully understand the role of voxelotor in treating SCD/SCA. In this review, we discuss the mechanisms, trials to date, and future treatment directions of voxelotor.

Keyword

Sickle cell disease; Sickle cell anemia; Voxelotor; Pharmacokinetics; Pharmacodynamics; Safety