13/10/2021
Adriana Mercedes
Summary of Voxelotor: A novel treatment for sickle cell disease
Sickle cell disease (SCD) is a genetic disorder that affects amino acids inside of the β-globin
chain of the hemoglobin (Hb) which results in the production of sickle-shaped Hb
(Hbs). This genetic disorder affects a vast majority of the populations in Sub-Sharan Africa,
India, Saudi Arabia, all Mediterranean countries, and the United States.
During these past 4 decades, the mortality rate for persons with SCD has increased a
lot; persons with SCD have a life expectancy of 54yrs old while persons that do not have CSD
have a life expectancy of 76yrs old; even with this mortality rate increasing it is still a dramatic
difference. There are currently no cures for this disorder but in 2019 a treatment called
Voxelotor was released after a long period of clinical trials and experimentation.
Voxelotor is an Hbs polymerization inhibitor that reverse binds to an α- chain of Hb and
controls the affinity of Hb for oxygen. Stabilizing RBCs (red blood cells) that are in an
oxygenated state promotes a blockage of Hb polymerization which prevents sickling and
destruction of RBCs. The topic of reducing RBC sickling improves RBC malformation which
leads to an extension of red blood cell half-life.
There were two trials that occurred with a random, double-blind, placebo-controlled
study in patients with SCD, and volunteers that did not have SCD were designated to evaluate
the safety and preliminary efficiency of voxelotor. All persons that were involved in these trials
were ages 18-60yrs old who weighed at least 50kg (110.2lbs); with elimination points of a Hb
count of 10.4g/dL, transfusions, or hospitalization within 30 days of the start date.
This study required multiple dosages of voxelotor ; a small tablet that can be taken with or
without food; the first was given at 28 days, the second at 90 days and finally a 6-month
extension study dosage was given. Persons who selected the 28-day study were split up into
3 dosing schedules and were randomly selected to receive voxelotor at 500mg/d; voxelotor
700mg/d, voxelotor 1000mg/d, or a copy placebo. Persons who selected the 90 days trial were
split up into 2 groups and were randomly selected to receive voxelotor 700mg/d, voxelotor
900mg/d, or a matching placebo. Persons in the 900mg versus placebo group were allowed
into the 6-month study extension but only after the first 90-days were completed.
Changes in Hb were noted in the 500 and 700mg groups but the 1000mg and placebo
group did not have any change. All given doses of voxelotor had a sickled red cell decline in
persons receiving voxelotor at 500mg, 700mg, and 1000mg. Overall this study shows no
safety concerns and it seems that it is a well-tolerated treatment. Voxelotor does have a heavy
warning regarding hypertension reactions due to some patients going into hypertension during
the first phase of this study. The long-term effects are currently being studied in other clinical
trials. This study shows that there is a significant improvement towards a cure to SCD, this
treatment is available to any person with SCD and it is recommended to take 1500mg once a
day, six days a week, and 1000mg one day a week. Voxelotors have shown benefit in reducing
acute complications that are related to SCD so it is the first medication that targets the
pathophysiology of this disorder. As a person with SCD, it is amazing to see how far we have
come with research, with voxelotor being a one-of-a-kind treatment, we are closer to a cure.
1. Herity LB, Vaughan DM, Rodriguez LR, Lowe DK. Voxelotor: A Novel Treatment for
Sickle Cell Disease. Annals of Pharmacotherapy. 2021;55(2):240-245.
doi:10.1177/1060028020943059