Estepp, JH;
Kalpatthi, R;
Woods, G;
Trompeter, S;
Liem, RI;
Sims, K;
Inati, A;
... Brown, C; + view all
(2022)
Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years.
Pediatric Blood and Cancer
, 69
(8)
, Article e29716. 10.1002/pbc.29716.
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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.
| Type: | Article |
|---|---|
| Title: | Safety and efficacy of voxelotor in pediatric patients with sickle cell disease aged 4 to 11 years |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/pbc.29716 |
| Publisher version: | http://dx.doi.org/10.1002/pbc.29716 |
| Language: | English |
| Additional information: | © 2022 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| Keywords: | clinical data, hemolytic anemia, pediatric, sickle cell disease, Anemia, Sickle Cell, Benzaldehydes, Biomarkers, Child, Child, Preschool, Female, Hemoglobin, Sickle, Hemolysis, Humans, Male, Pyrazines, Pyrazoles |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10184643 |
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