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. 2022 Aug;69(8):e29716.
doi: 10.1002/pbc.29716. Epub 2022 Apr 21.

Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years

Jeremie H Estepp  1 , Ram Kalpatthi  2 , Gerald Woods  3 , Sara Trompeter  4 , Robert I Liem  5 , Kacie Sims  6 , Adlette Inati  7 , Baba P D Inusa  8 , Andrew Campbell  9 , Connie Piccone  10 , Miguel R Abboud  11 , Kim Smith-Whitley  12 , Sandra Dixon  13 , Margaret Tonda  13 , Carla Washington  13 , Noelle M Griffin  13 , Clark Brown  14
Affiliations

Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years

Jeremie H Estepp et al. Pediatr Blood Cancer. 2022 Aug.

Abstract

Background: Sickle cell disease (SCD) is a devastating, multisystemic disorder that affects millions of people worldwide. The earliest clinical manifestations of SCD can affect infants as young as 6 months of age, and pediatric patients are at risk for acute and life-threatening complications. Early intervention with treatments that target the underlying pathophysiological mechanism of SCD, sickle hemoglobin (HbS) polymerization, are expected to slow disease progression and circumvent disease-associated morbidity and mortality.

Procedure: The HOPE-KIDS 1 trial (NCT02850406) is an ongoing four-part, phase 2a, open-label, single- and multiple-dose study to evaluate the pharmacokinetics, efficacy, and safety of voxelotor-a first-in-class HbS polymerization inhibitor-in patients aged 6 months to 17 years with SCD. Initial findings from a cohort of 45 patients aged 4 to 11 years who received voxelotor treatment for up to 48 weeks are reported.

Results: Hemoglobin (Hb) response, defined as a >1.0 g/dl increase from baseline, was achieved at week 24 by 47% (n = 16/34) of patients with Hb measurements at baseline and week 24. At week 24, 35% (n = 12/34) and 21% (n = 7/34) of patients had a >1.5 g/dl increase and a >2.0 g/dl increase from baseline in Hb concentration, respectively. Concurrent improvements in hemolytic markers were observed. Voxelotor was well tolerated in this young cohort, with no newly emerging safety signals.

Conclusions: Based on its mechanism as an HbS polymerization inhibitor, voxelotor improves Hb levels and markers of hemolysis and has the potential to mitigate SCD-related complications; these results support its use in patients aged ≥4 years.

Keywords: clinical data; hemolytic anemia; pediatric; sickle cell disease.

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References

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