Hematology · 3 h ago
RESOLVE trial finds no benefit of voxelotor for sickle cell leg ulcers
In the phase 3 RESOLVE trial, 88 participants with sickle cell disease and active leg ulcers were randomised to voxelotor or placebo for 12 weeks. Ulcer resolution rates were similar, and voxelotor was subsequently withdrawn from all markets after safety concerns emerged across trials.
- Ulcer resolution was 6.7% with voxelotor and 7.0% with placebo.
- The primary endpoint was not met.
- Voxelotor was withdrawn from all markets globally.
- No fatal event was considered treatment-related.
RESOLVE was a phase 3, randomised, double-blind, placebo-controlled trial in participants aged 12 years or older with sickle cell disease (HbSS or HbSβ⁰-thalassaemia) and at least one active lower-extremity ulcer. Participants in Kenya, Nigeria and Brazil received voxelotor 1500 mg (n=45) or placebo (n=43) for 12 weeks. The primary endpoint was complete resolution of all target ulcers at week 12.
Resolution occurred in 3 of 45 participants receiving voxelotor (6.7%) and 3 of 43 receiving placebo (7.0%; p>0.99), so the primary endpoint was not met. The most common sickle cell-related treatment-emergent adverse event was sickle cell anaemia with crisis, reported in 44.4% of the voxelotor group and 25.6% of the placebo group during the randomised period. Eleven participants had fatal events; none was considered treatment-related by the investigators.
Dosing was paused in May 2024 after preliminary safety signals across four voxelotor trials, including RESOLVE. The trial was discontinued in September 2024 after voxelotor was withdrawn from all markets globally. The findings do not support benefit for leg-ulcer resolution; interpretation of safety outcomes should account for the trial’s discontinuation and the broader safety review.
In practice
For people aged 12 years or older with HbSS or HbSβ⁰-thalassaemia and active leg ulcers, RESOLVE found no evidence that 12 weeks of voxelotor improved complete ulcer resolution compared with placebo: rates were 6.7% and 7.0%, respectively. The trial was discontinued after voxelotor was withdrawn from all markets globally following safety signals across trials. These results do not support voxelotor for this ulcer indication; the trial findings should be interpreted in the context of its discontinuation and the broader safety review.
AI-generated clinical interpretation · Not editor-reviewed
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British Journal of Haematology: Phase 3, randomised, placebo‐controlled trial of voxelotor for the resolution of leg ulcers in sickle cell disease: RESOLVE ↗This is an automated AI-condensed summary that has not yet been reviewed by an editor. Always consult the full item at the original source.