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ASH 2025 | Rheological effects of voxelotor in sickle cell disease: the HEMOPROVE trial
Gonzalo De Luna, MD, Henri-Mondor University Hospital, Créteil, France, discusses 12-month rheological findings from the HEMOPROVE study (NCT05199766), a single-arm trial assessing the effects of voxelotor in patients with sickle cell disease (SCD). Treatment-related improvements in red blood cell deformability and aggregation were observed, contributing to reduced sickling in patients. However, the associated increase in hematocrit elevated blood viscosity, which may contribute to increased risk of vaso-occlusive crises (VOCs). This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
This is our abstract concerning the results about the 12 months of voxelotor treatment. It’s a phase 2 trial, the HEMPROVE trial, and you know that voxelotor is an anti-sickling polymerization inhibitor approach in sickle cell disease that improves hemoglobin level and red blood cell properties. However, its impact on blood viscosity raises questions about the potential vaso-occlusive crisis risk...
This is our abstract concerning the results about the 12 months of voxelotor treatment. It’s a phase 2 trial, the HEMPROVE trial, and you know that voxelotor is an anti-sickling polymerization inhibitor approach in sickle cell disease that improves hemoglobin level and red blood cell properties. However, its impact on blood viscosity raises questions about the potential vaso-occlusive crisis risk. We have evaluated 19 patients treated with voxelotor, 1,500 milligram daily, for 48 weeks. After 12 months of treatment, hemoglobin increased significantly from 7.3 to 9 g per deciliter, and hematocrit rose from 21% to 26%. Red blood cell deformability improved under both oxygenated and deoxygenated conditions, and red blood cell aggregation normalized. This change correlated with reduced sickling. However, blood viscosity at high shear rates increased from 4.6 to 5.8 centipoise, mainly due to a higher hematocrit. We know also in this call that four patients experienced a vaso-occlusive crisis during the follow-up, three of them complicated by acute chest syndrome. These patients showed a higher baseline reticulocyte count and lacked improvement in the hematocrit to viscosity ratio. In conclusion, voxelotor enhances the red blood cell rheology and oxygen delivery, but also raises blood viscosity, which may contribute to vaso-occlusive risk. Monitoring viscosity should be integrated in future therapeutic strategies like this kind of anti-sickling approach like voxelotor or other drugs like, for example, mitapivat or etavopivat in the future.
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