Author(s)

Shuyang Jin, Yujia Xu, Jieyu Yu

Corresponding Author

Yujia Xu

ABSTRACT

Sickle cell disease has been affecting millions of people all around the world, but it was never the focus in pharmaceutical researches until recent years. A novel 2019 FDA-approved drug, voxelotor, was developed as a silver lining for the millions who suffer from sickle cell disease. Voxelotor reversibly binds to hemoglobin to prevent red blood cells from sickling and destruction. Phase 1/2 and phase 3 clinical trials both revealed increased hemoglobin levels and reduced sickles cells in sickle cell disease patients. Voxelotor forms covalent bonds with the N-terminal α chain of Hb to increase its oxygen affinity, which improved patient clinical performance. Single doses of voxelotor are well tolerated in both healthy volunteers and SCD patients, but multiple doses in healthy subjects revealed more severe side effects, such as jaundice and leg ulcers. Although common adverse effects have been identified, more researches about side effects need to be studied. This review will first introduce the background of the disease and voxelotor, including basic drug properties. Followed by the efficacy of voxelotor and adverse reactions as well as risks associated with it.

KEYWORDS

Sickle cell disease (SCD), Voxelotor, hemoglobin (Hb), oxygen affinity, side effects