Systematic review of voxelotor: a first ‐in‐class sickle hemoglobin polymerization inhibitor for management of sickle cell disease

This article reviews published data about voxelotor treatment of SCD based on a search of Medline, Embase, and International Pharmaceutical Abstracts. In a phase I/II trial, voxelotor demonstrated a dose ‐dependent pharmacokinetic and pharmacodynamic response and was well‐tolerated in healthy volunteers and patients with SCD. In a multi‐center, randomized, double‐blind, phase III trial (HOPE trial), a significantly higher percentage of patients randomized to voxelotor had increased hemoglobi n (> 1g/dL from baseline) compared to placebo. A greater reduction of hemolytic markers was also observed in the voxelotor ‐treated group, whereas the incidence of adverse effects was comparable. Three case series or reports also demonstrated the efficacy and safety of voxelotor use in a limited number of SCD patients in the real‐world situation, although one patient with SCD, severe anemia, and a history of autoant ibody‐mediated hemolysis failed to respond to voxelotor. An ongoing trial (HOPE‐KIDS) is designed to establish the use of voxelotor in younger pediatric patients with SCD. There is a theoretical concern that voxelotor may impair oxygen delivery, due to modification of the oxygen affinity of hemo globin, which needs to be further evaluated. As a first‐in‐class hemoglobin modulator, voxelotor offers a new treatment option targeting the root cause of SCD.
Source: Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Category: Drugs & Pharmacology Authors: Tags: REVIEW OF THERAPEUTICS Source Type: research