HOPE Kids 2: Phase 3, Randomized Trial of Voxelotor in Children With SCD and Conditional Cerebral Blood Flow Velocities

) and conditional CBFV (170 to < 200 cm/s) were randomized 1:1 to voxelotor (N = 120) or placebo (N = 116) for 96 weeks; 195 (83%) were in sub-Saharan Africa. The primary endpoint, CBFV change from baseline to Week 24, was significantly greater with voxelotor (least-squares mean change: voxelotor [n = 114] -12.06 cm/s, placebo [n = 108] -4.29 cm/s; difference -7.77 cm/s; 95% CI -13.18 to -2.37; p = 0.0048), with significant difference sustained through Week 48. Hemoglobin levels increased at Weeks 24 and 48 with voxelotor. Drug administration was paused in May 2024 when an imbalance of deaths was observed between treatment groups; subsequently, the trial discontinued when all active voxelotor trials were discontinued in September 2024. At study end, median (range) exposure was 84 (3-104) weeks for voxelotor and 84 (3-106) weeks for placebo. The most common SCD-related treatment-emergent adverse event was sickle cell anemia with crisis (voxelotor 59.2%; placebo 37.9%). All deaths (voxelotor n = 8; placebo n = 2) were considered unrelated to study drug by treating investigators. Overall, voxelotor showed CBFV reduction in children with SCD and conditional CBFV, suggesting HbS polymerization inhibition has a potential therapeutic role for this group; nevertheless, additional studies evaluating potential regional risks for sickle cell anemia with crisis or mortality are warranted. Trial Registration: ClinicalTrials.gov identifier: NCT04218084.

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Publication Details

Journal
American Journal of Hematology
Published
2026-08-28
DOI
https://doi.org/10.1002/ajh.70457
Primary Topic
Hemoglobinopathies and Related Disorders
Type
article
Field-Weighted Citation Impact
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article

HOPE Kids 2: Phase 3, Randomized Trial of Voxelotor in Children With SCD and Conditional Cerebral Blood Flow Velocities

Fenella J. Kirkham, Adeseye Michael Akinsete, Paul Telfer, Videlis Nduba et al.
American Journal of Hematology
Hemoglobinopathies and Related Disorders
article

HOPE Kids 2: Phase 3, Randomized Trial of Voxelotor in Children With SCD and Conditional Cerebral Blood Flow Velocities

Fenella J. Kirkham, Adeseye Michael Akinsete, Paul Telfer, Videlis Nduba, Yasser Wali, Mohammed Essa, Vivian Paintsil, H. Hassab, Halima Bello‐Manga, Venée N. Tubman, Diana Hanna, R. Clark Brown, Jeremy W. Rupon, Jennifer Doss, Shehu U. Abdullahi, Catherine I. Segbefia, Mark W. Davis, Anne Hickman, Sandy Dixon, Amal El-Beshlawy, Jessie Githang’a, the HOPE Kids 2 Investigators, Bernhards Ogutu, Biobele Brown, Azza Tantawy, Iheanyi Okpala
article en

Abstract

) and conditional CBFV (170 to < 200 cm/s) were randomized 1:1 to voxelotor (N = 120) or placebo (N = 116) for 96 weeks; 195 (83%) were in sub-Saharan Africa. The primary endpoint, CBFV change from baseline to Week 24, was significantly greater with voxelotor (least-squares mean change: voxelotor [n = 114] -12.06 cm/s, placebo [n = 108] -4.29 cm/s; difference -7.77 cm/s; 95% CI -13.18 to -2.37; p = 0.0048), with significant difference sustained through Week 48. Hemoglobin levels increased at Weeks 24 and 48 with voxelotor. Drug administration was paused in May 2024 when an imbalance of deaths was observed between treatment groups; subsequently, the trial discontinued when all active voxelotor trials were discontinued in September 2024. At study end, median (range) exposure was 84 (3-104) weeks for voxelotor and 84 (3-106) weeks for placebo. The most common SCD-related treatment-emergent adverse event was sickle cell anemia with crisis (voxelotor 59.2%; placebo 37.9%). All deaths (voxelotor n = 8; placebo n = 2) were considered unrelated to study drug by treating investigators. Overall, voxelotor showed CBFV reduction in children with SCD and conditional CBFV, suggesting HbS polymerization inhibition has a potential therapeutic role for this group; nevertheless, additional studies evaluating potential regional risks for sickle cell anemia with crisis or mortality are warranted. Trial Registration: ClinicalTrials.gov identifier: NCT04218084.

American Journal of Hematology
Ain Shams University (EG), University of Nairobi (KE), University of Ghana (GH), Cairo University (EG), Strathmore University (KE), Pfizer (United States) (US), University of Ibadan (NG), King Saud bin Abdulaziz University for Health Sciences (SA), Zagazig University (EG), University of Lagos (NG), Barts Health NHS Trust (GB), Kwame Nkrumah University of Science and Technology (GH), Kenya Medical Research Institute (KE), Kaduna State University (NG), Texas Children's Hospital (US), University of Nigeria Teaching Hospital (NG), University College London (GB), Sultan Qaboos University (OM), Alexandria University (EG), Bayero University Kano (NG)
Pfizer
Good health and well-being
Openalex Percentile: Top 11%
Hemoglobinopathies and Related Disorders
DOIOpen Access PDFOpenAlex
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