The median age of participants was 24 years and baseline hemoglobin (Hb) range was 5.5 to 10.5 g/dL.
Approximately 65% of enrolled patients were taking hydroxyurea at the time of enrollment; those on stable hydroxyurea doses continued therapy throughout the trial.
For voxelotor, the response rate was 51% compared with 6.5% for the placebo group.
Adverse events that occurred in >10% of patients include headache, diarrhea, abdominal pain, nausea, rash, fatigue, and pyrexia.
The recommended starting dosage is 1,500 mg orally once daily.
Voxelotor approved for the treatment of sickle cell disease in adults and pediatric patients 12 years or older.
Trade names Oxbryta.
A polymerization inhibitor.
A once-daily oral therapy that modulates hemoglobin affinity for oxygen by binding to hemoglobin S and stabilizing it, to treat patients with sickle cell disease (SCD) aged 12 and older.
Voxelotor inhibits hemoglobin polymerization, reduces sickling and improves red blood cell survival.
The drug binds covalently to the N– terminal of alpha globulin in oxyhemoglobin, S and F, resulting in stabilization of a conformstion of hemoglobin that cannot polymerize, as well as in a marked increase in overall oxygen affinity.
The drug is a potent inhibitor of red cell, signaling, which depends on the D oxygenation of hemoglobin.
It stabilizes the sickle hemoglobin molecule as a monomer in its high oxygen state.
Deoxygenated sickle hemoglobin polymerizes and drives the pathophysiology of sickle cell disease,
Direct inhibition of hemoglobin polymerization can modify disease outcome.
Voxelotor is a hemoglobin S polymerization inhibitor.
Thus, polymerization of the hemoglobin molecules is inhibited, which decreases the amount of red blood cell damage.
It is proposed that because oxygenated HbS cannot polymerize, modifying HbS to increase the proportion of oxygenated to deoxygenated HbS in red blood cells would alter disease severity.
First-in-class therapy regulates the affinity of hemoglobin (Hb) for oxygen, resulting in a decrease in the concentration of deoxygenated sickle hemoglobin (HbS), which forms polymers.
Other beneficial include improved rheology and reduced hemolysis, as well as a boost to the oxygen-carrying capacity of the sickle hemoglobin molecules.
All adult patients in a preliminary study had rapid increases in serum hemoglobin, with increases of at least 1 g/dL.
Studies demonstrate that voxelotor inhibits red blood cell sickling, improves red blood cell deformability and improves the blood’s ability to flow.
The approval was based on the results of a clinical trial with 274 patients with SCD.
This approval is based on results from the phase III HOPE trial, in which 274 patients were randomized to receive either:
voxelotor 1,500 mg (n=90) voxelotor 900 mg (n=92) placebo (n=92)
92 patients received 900 mg of voxelotor, and 92 patients received a placebo: Effectiveness was based on an increase in hemoglobin response rate in patients who received 1500 mg of voxelotor, which was 51.1% for these patients compared to 6.5% in the placebo group.
In a study of 274 participants once daily voxelotor versus placebo resulted in significant increased hemoglobin levels and reduced markers of hemolysis(HOPE Trial Investigators).
The median age of participants was 24 years and baseline hemoglobin (Hb) range was 5.5 to 10.5 g/dL.
Approximately 65% of enrolled patients were taking hydroxyurea at the time of enrollment; those on stable hydroxyurea doses continued therapy throughout the trial.
The trial examined was the number of hospitalizations for pain from vaso-occlusive crises (VOCs):there was a 67% reduction in hospitalizations among the participants,.
The total number of red blood cell transfusions required by the study population declined by 60% over 24 weeks.
Adverse events that occurred in >10% of patients include headache, diarrhea, abdominal pain, nausea, rash, fatigue, and pyrexia.
Studies have revealed no significant effect on the frequency or severity of vaso-occlusive events.
The recommended starting dosage is 1,500 mg orally once daily.