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Clinical Trial
. 2025 Jan;100(1):78-84.
doi: 10.1002/ajh.27522. Epub 2024 Nov 20.

Effect of voxelotor on cerebral perfusion and cerebral oxygen metabolism and cardiac stress in adult patients with sickle cell disease

Kadère Konté  1   2 , Liza Afzali-Hashemi  1   2 , Koen P A Baas  2 , Anouk Schrantee  2 , John C Wood  3 , Erfan Nur  1   4 , Aart J Nederveen  2 , Bart J Biemond  1
Affiliations
Clinical Trial

Effect of voxelotor on cerebral perfusion and cerebral oxygen metabolism and cardiac stress in adult patients with sickle cell disease

Kadère Konté et al. Am J Hematol. 2025 Jan.

Abstract

Sickle cell disease (SCD) is complicated by silent cerebral infarcts (SCIs), for which anemia is an important risk factor. Despite normal oxygen delivery (OD), cerebral vascular reserve (CVR), and cerebral metabolic rate of oxygen (CMRO2) are diminished in SCD, possibly causing the formation of SCIs. Voxelotor inhibits polymerization by increasing the hemoglobin oxygen binding, ameliorating hemolytic anemia. Furthermore, anemia is related to cardiac complications. Our aims were to assess the effect of voxelotor on markers of cerebral perfusion, cerebral oxygen metabolism, and markers of cardiac stress in SCD patients. Cerebral hemodynamics and oxygen metabolism were measured with MRI before and after 3 months of voxelotor treatment (1500 mg/day) in 18 adults with SCD (HbSS/HbSβ0-thalassemia). Hemoglobin levels significantly increased (p = .001) and markers of hemolysis decreased (p < .05). OD increased from 6.5 (IQR, 6.0-7.1) mL O2/100 g/min to 8.1 (IQR, 7.2-8.7) mL O2/100 g/min (p = .001). CBF and CVR did not change. CMRO2 decreased from 2.0 (IQR, 1.9-2.1) mL O2/100 g/min to 1.9 (IQR, 1.6-2.1) mL O2/100 g/min (p = .03). N-terminal pro-B type natriuretic peptide (NT-proBNP) levels decreased (p = .048) and maximum tricuspid regurgitation flow velocity (TRVmax) normalized in all but one patient with increased TRVmax. Voxelotor treatment in patients with severe SCD did not decrease CBF despite increased Hb levels. Cerebral oxygen metabolism slightly decreased, despite raised OD, most likely due to drug-induced increase in oxygen binding. Nonetheless, voxelotor improved clinically validated markers of cardiac stress.

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Conflict of interest statement

John C. Wood is Consultant to Agios, Celgene/BMS, Hillhurst, Imago Biosciences, Pharmacosmos, World Care Clinical, part of the Regeneron, Vifor, and Bluebird Bio, and has received a research grant from Philips. EN is a member of an entity's Board of Directors or advisory committee of Novartis and received research Funding. Bart J. Biemond is part of ad hoc advisory committees of CSL Behring, Novo Nordisk, Celgene/BMS, Pfizer and Novartis and has received research funding from Novartis, BMS, GBT/Pfizer, and Sanquin. Liza Afzali‐Hashemi, Koen P. A. Baas, Aart J. Nederveen, and Kadère Konté have no disclosures to report.

Figures

FIGURE 1
FIGURE 1
Effects of 3 months of treatment with voxelotor on markers of cerebral hemodynamics. [Color figure can be viewed at wileyonlinelibrary.com]
FIGURE 2
FIGURE 2
Effects of 3 months of treatment with voxelotor on markers of cerebral hemodynamics (OD) and oxygen metabolism (OEF and CMRO2). [Color figure can be viewed at wileyonlinelibrary.com]
See this image and copyright information in PMC

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