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

In 30 seconds

HOPE Kids 2 was a phase 3, multicenter, double-blind, placebo-controlled randomized trial of voxelotor in children aged 2 to <15 years with sickle cell disease (HbSS/HbSβ⁰) and conditional cerebral blood flow velocities (CBFV). Participants received voxelotor or placebo for up to 96 weeks. At Week 24, CBFV decreased more with voxelotor than placebo: least-squares mean change -12.06 cm/s versus -4.29 cm/s, a difference of -7.77 cm/s (95% CI -13.18 to -2.37; p = 0.0048). Treatment was paused after an imbalance in deaths was observed, and the trial was subsequently discontinued.

Key findings

• At Week 24, CBFV change was -12.06 cm/s with voxelotor and -4.29 cm/s with placebo; difference -7.77 cm/s (95% CI -13.18 to -2.37; p = 0.0048).
• The CBFV difference remained significant through Week 48, and hemoglobin levels increased with voxelotor at Weeks 24 and 48.
• Sickle cell anemia with crisis was the most common SCD-related treatment-emergent adverse event (voxelotor 59.2%; placebo 37.9%).
• Eight deaths occurred in the voxelotor group and two in the placebo group; investigators considered all unrelated to study drug.

Why it matters

Conditional CBFV is associated with elevated stroke risk in children with SCD, making the observed reduction a clinically relevant physiological signal. However, the mortality imbalance and higher frequency of sickle cell anemia with crisis complicate interpretation of potential benefit. The findings underscore the need to assess both cerebrovascular measures and clinical safety outcomes when evaluating therapies in this population.

What to keep in mind

The trial was discontinued after an imbalance in deaths was observed and active voxelotor trials were discontinued, limiting interpretation of the planned follow-up. The abstract does not establish whether the CBFV change translates into fewer strokes.