Oxbryta directly binds to HbS molecules
Dose-dependent binding of Oxbryta increases oxygen affinity, inhibiting HbS polymerization
Nonclinical studies suggest Oxbryta may reduce RBC sickling
Nonclinical studies also suggest Oxbryta may reduce whole blood viscosity
Clinical studies* have shown that Oxbryta improves anemia† and reduces hemolysis‡
*Oxbryta is approved under accelerated approval based on increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).1
†As measured by a Hb increase of >1 g/dL from baseline to week 24 vs placebo (51% vs 7%) in patients ≥12 years of age.1
‡As demonstrated by statistically significant reductions in indirect bilirubin and percent reticulocyte count in patients ≥12 years of age (-26% and -25% placebo-adjusted mean change from baseline at 24 weeks, respectively).1
Oxbryta - The first and only therapy designed to directly intervene in the sickle cell disease cascade including anemia and hemolysis.1,2
Sickle cell disease is a group of inherited disorders that is caused by a single point mutation in the beta globin gene resulting in sickled hemoglobin, designated hemoglobin S (also known as HbS).3
Hemoglobin S molecules have a lower affinity for oxygen.4-7
Once deoxygenated, HbS molecules tend to bind to one another, or polymerize, forming into long, rigid rods that deform red blood cells into a distinctive sickle shape.4-7
HbS polymerization is the root cause of sickling.4-7
It starts a domino-like cascade effect of complications, including anemia4-7 and hemolysis.3,4
Hemolysis releases red blood cell contents into the blood which promote activation of neutrophils, platelets, and endothelial cells.3,4
The hemolytic breakdown of sickled red blood cells leads to anemia, impairing oxygen delivery.3,4,8
Sickled red blood cells, platelets, and neutrophils adhere to each other and to the activated endothelium, contributing to the formation of vaso-occlusions that block blood flow.3,4,8
This continuous cycle of HbS polymerization, anemia, hemolysis, and vaso-occlusion lead to progressive vessel injury, a drop in functional red blood cells, and downstream consequences.3,4,9-12
Oxbryta is a once daily, oral medication designed specifically to intervene in the sickle cell disease cascade and is the first and only direct hemoglobin S polymerization inhibitor.1
Indicated in adults and pediatric patients, it can be taken with or without hydroxyurea for the treatment of sickle cell disease.1
Oxbryta binds directly to hemoglobin S, allowing oxygen affinity to normalize and inhibit polymerization.1
Studies on the blood of patients taking Oxbryta have shown reduced red blood cell sickling, improved red blood cell deformability, and reduced whole blood viscosity.1
By increasing the affinity for oxygen and directly inhibiting HbS polymerization, Oxbryta intervenes in the domino-like cascade of effects caused by sickling.1
Specifically, Oxbryta helps to improve anemia as measured by increases in hemoglobin.1,2
Oxbryta also helps reduce hemolysis, as measured by reductions in bilirubin and percent reticulocyte count.1
In summary, while some medications may indirectly address polymerization, only Oxbryta directly inhibits this underlying issue of hemoglobin S polymerization.1,2
Now you can prescribe once-daily oral Oxbryta for your patients in order to intervene in the sickle cell disease cascade and subsequent downstream consequences of anemia and hemolysis.1,2
INDICATIONS AND USAGE
Oxbryta is indicated for the treatment of sickle cell disease (SCD) in adults and pediatric patients 4 years of age and older.
This indication is approved under accelerated approval based on increase in hemoglobin (Hb). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
Oxbryta is contraindicated in patients with a history of serious drug hypersensitivity reaction to voxelotor or excipients. Clinical manifestations may include generalized rash, urticaria, mild shortness of breath, mild facial swelling, and eosinophilia.
WARNINGS AND PRECAUTIONS
Serious hypersensitivity reactions after administration of Oxbryta have occurred in <1% of patients treated. Clinical manifestations may include generalized rash, urticaria, mild shortness of breath, mild facial swelling, and eosinophilia.
If hypersensitivity reactions occur, discontinue Oxbryta and administer appropriate medical therapy. Do not reinitiate Oxbryta in patients who experience these symptoms with previous use.
Laboratory Test Interference
Oxbryta administration may interfere with measurement of Hb subtypes (HbA, HbS, and HbF) by high-performance liquid chromatography (HPLC). If precise quantitation of Hb species is required, chromatography should be performed when the patient has not received Oxbryta therapy in the immediately preceding 10 days.
Clinical Trials Experience
Adults and Pediatric Patients 12 Years of Age and Older
Serious adverse reactions occurred in 3% (3/88) of patients receiving Oxbryta 1,500 mg, which included headache, drug hypersensitivity, and pulmonary embolism occurring in 1 patient each. Permanent discontinuation due to an adverse reaction (Grades 1-4) occurred in 5% (4/88) of patients who received Oxbryta 1,500 mg.
The most common adverse reactions (≥10%) in patients receiving Oxbryta 1,500 mg with a difference of >3% compared to placebo: Headache (32% vs. 25%), Diarrhea (23% vs. 11%), Abdominal Pain (23% vs. 16%), Nausea (19% vs. 10%), Rash (15% vs. 11%), and Pyrexia (15% vs. 8%).
Pediatric Patients 4 to <12 Years
The safety of Oxbryta in pediatric patients 4 to <12 years with SCD was evaluated in an open‑label, Phase 2 study. In this study, 45 patients 4 to <12 years of age received doses of Oxbryta tablets for oral suspension based on weight at baseline. Thirty‑five patients received Oxbryta for 24 weeks and 26 patients for 48 weeks. The most common adverse reactions (>10%) reported in pediatric patients 4 to <12 years were pyrexia (36%), vomiting (33%), rash (20%), abdominal pain (18%), diarrhea (18%), and headache (18%).
The overall safety profile of Oxbryta in pediatric patients 4 to <12 years was similar to that seen in adults and pediatric patients 12 years and older.
Strong or Moderate CYP3A4 Inducers
Coadministration of strong or moderate CYP3A4 inducers may decrease voxelotor plasma and whole blood concentrations and may lead to reduced efficacy. Avoid coadministration of Oxbryta with strong or moderate CYP3A4 inducers. Increase the Oxbryta dosage when coadministration with a strong or moderate CYP3A4 inducer is unavoidable.
Sensitive CYP3A4 Substrates
Voxelotor increased the systemic exposure of midazolam (a sensitive CYP3A4 substrate). Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. If unavoidable, consider dose reduction of the CYP3A4 substrate(s).
USE IN SPECIFIC POPULATIONS
Because of the potential for serious adverse reactions in the breastfed child, including changes in the hematopoietic system, advise patients not to breastfeed while taking Oxbryta and for at least 2 weeks after the last dose.
Recommended Dosage for Hepatic Impairment
Severe hepatic impairment increases voxelotor exposures. For severe hepatic impairment (Child Pugh C) reduce dose to 1,000 mg orally once daily for adults and pediatric patients ≥ 12 years. Dose reduction for pediatric patients 4 to <12 years is dependent on body weight (please refer to Table 2 in the Full Prescribing Information).
Please see Full Prescribing Information for more information about Oxbryta.
In a Phase 1/2, randomized, double-blind, placebo-controlled study of voxelotor, patients with SCD (HbSS or HbSβ0 thalassemia), aged 18-60 years, were enrolled in either a 28-day cohort (n=38) or a 90-day cohort (n=16). In the 90-day cohort, voxelotor was administered as multiple doses, 700 mg or 900 mg. This analysis was done at 90 days.3
Median percent change in sickled RBC count from baseline at day ≥903
Percentage of sickled RBCs was analyzed from blood smears by 2 independent blinded readers. Six independent microscopy fields were randomly selected and >500 RBCs from >3 different fields were counted per blood smear. Elongated, crescent-shaped RBCs with tapering of opposite ends that culminated in a point were counted as sickled. Reductions in sickled RBCs of 73% and 79% from baseline were seen in patients receiving 700 mg and 900 mg voxelotor, respectively.3
HbSS = homozygous hemoglobin S; HbSβ0 = hemoglobin sickle beta zero.
Voxelotor, day 90
Placebo, day 90