Voxelotor for the treatment of sickle cell disease in pediatric patients

ABSTRACT

Introduction

Sickle cell disease (SCD) describes a group of heritable blood disorders caused by the polymerization of sickle hemoglobin (HbS). HbS polymerization leads to anemia and vaso-occlusion, a process that impedes delivery of oxygen to tissues throughout the body, resulting in end-organ damage (EOD). Given the lifelong complications associated with SCD, identification and treatment of early symptoms in childhood is increasingly important. Voxelotor is an oral therapy that inhibits the polymerization of HbS and offers a unique therapeutic mechanism to reduce the causes of EOD. Voxelotor was approved in December 2021 for the treatment of SCD in patients aged ≥4 years.

Areas covered

Clinical data on the use of voxelotor in pediatric patients with SCD is reviewed. Ongoing studies examining the clinical efficacy and safety profile of voxelotor in pediatric patients are compared with similar clinical outcomes in adults with SCD. Planned studies of voxelotor in children are also discussed.

Expert opinion

Voxelotor provides a unique therapeutic option to target the root causes of EOD and can potentially be used alongside other SCD therapies. Future studies directly observing the impact of voxelotor on EOD will be important for determining treatment strategies.

KEYWORDS:

• end-organ damage
• hemoglobin
• sickle cell disease
• voxelotor

Article highlights

• Sickle cell disease (SCD) manifests early in life and can lead to overt symptoms and silent end-organ damage; therefore, disease-modifying therapies for pediatric patients are exceedingly important in this lifelong disease.

• Voxelotor is a first-in-class polymerization inhibitor of sickle hemoglobin that has previously been shown to increase hemoglobin levels and reduce erythrocyte hemolysis in patients with SCD.

• Voxelotor efficacy and safety results from the HOPE-KIDS 1 trial in patients with SCD aged 4 to 11 years were similar to results observed in adult patients and patients aged ≥12 years with SCD from the pivotal HOPE trial.

• Post-marketing surveillance and real-world evidence have indicated improvements in symptoms of SCD and overall quality of life in patients receiving voxelotor.

• As a result of the HOPE-KIDS 1 trial, voxelotor is approved for use in the United States in patients as young as 4 years of age and in the European Union and United Arab Emirates in patients as young as 12 years of age; voxelotor is available as tablets for oral use and as tablets for oral suspension.

• Although a theoretical decrease in oxygen offloading due to greater hemoglobin-oxygen affinity with voxelotor has been suggested, clinical trial evidence and real-world clinical experience show no evidence of insufficient oxygen delivery.

Declaration of Interest

C Brown declares consultancy work for Global Blood Therapeutics, Inc. M Tonda is an employee and equity owner of Global Blood Therapeutics, Inc. MR Abboud is a consultant for Novartis and Novo Nordisk and receives additional research funding from Eli Lilly and Modus Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A peer reviewer on this manuscript is a speaker and consultant for Global Blood Therapeutics, Inc. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was developed with assistance from a professional medical writer, supported by Global Blood Therapeutics Inc.