Randomized trial reveals voxelotor reduces cerebral blood flow velocity in children with sickle cell disease, highlighting potential benefits alongside unexpected safety concerns.
Key Points
Evaluate the efficacy and safety of voxelotor compared to placebo in reducing conditional cerebral blood flow velocities in pediatric sickle cell disease.
Phase 3 randomized trial (NCT04218084) enrolling 236 children with sickle cell disease and conditional cerebral blood flow velocities (170 to <200 cm/s), assigned 1:1 to voxelotor (N = 120) or placebo (N = 116) for a planned 96 weeks.
Conducted predominantly in sub-Saharan Africa (83%), assessing the primary endpoint of cerebral blood flow velocity change from baseline to Week 24, with treatment exposure reaching a median of 84 weeks.
Voxelotor produced a significantly greater reduction in cerebral blood flow velocity at Week 24 versus placebo (least-squares mean change: -12.06 cm/s [n = 114] vs. -4.29 cm/s [n = 108]; difference: -7.77 cm/s; 95% CI, -13.18 to -2.37; p = 0.0048), sustained through Week 48.
Sickle cell anemia with crisis occurred in 59.2% of voxelotor recipients compared to 37.9% of placebo recipients.
The trial was terminated early following an observed imbalance in deaths (voxelotor n = 8 vs. placebo n = 2), though all deaths were assessed by treating investigators as unrelated to the study drug.