Oxbryta is specifically designed to intervene in the
sickle cell disease (SCD) cascade1

The unique mechanism of action (MOA) of Oxbryta directly inhibits the root cause of sickling in SCD1,2

Voxelotor binding directly to your patient's hemoglobin S (HbS) molecules.

Bind

Oxbryta binds directly to your patient’s hemoglobin S (HbS) molecules

Voxelotor dose‐dependent binding increases oxygen affinity, inhibiting polymerization of the HbS molecule.

Inhibit

This dose-dependent binding increases oxygen (O2) affinity, inhibiting polymerization of the HbS molecule

Nonclinical studies suggest that voxelotor may inhibit red blood cell (RBC) sickling, improve RBC deformability, and reduce whole blood viscosity.

Reduce

Nonclinical studies suggest that Oxbryta may inhibit red blood cell (RBC) sickling, improve RBC deformability, and reduce whole blood viscosity

Improve anemia (as measured by an increase in hemoglobin) and reduce hemolysis (as measured by indirect bilirubin and percent reticulocyte count).

Improve

Improve anemia (as measured by an increase in hemoglobin) and reduce hemolysis (as measured by indirect bilirubin and percent reticulocyte count)

  • Hemoglobin S (HbS) molecules have a lower affinity for O2
  • When HbS releases oxygen, it can polymerize into long, rigid rods
  • These long, rigid rods deform the RBCs into sickled RBCs driving multiple interconnected pathologies

See how Oxbryta works

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 12 years of age and older, 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 andhemolysis.1,2

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease (SCD) in adults and pediatric patients 12 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
CONTRAINDICATIONS

Oxbryta is contraindicated in patients with a history of serious drug hypersensitivity reaction to voxelotor or excipients.

WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions

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 by (HbA, HbS, and HbF) HPLC. If precise quantitation of Hb species is required, chromatography should be performed when the patient is not receiving Oxbryta therapy.

ADVERSE REACTIONS
Clinical Trials Experience

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.

Adverse Reactions (≥10%) in patients receiving Oxbryta with a difference of >3% compared to placebo: Headache (26% vs. 22%), Diarrhea (20% vs. 10%), Abdominal Pain (19% vs. 13%), Nausea (17% vs. 10%), Fatigue (14% vs. 10%), Rash (14% vs. 10%), and Pyrexia (12% vs. 7%).

Drug interactions

Sensitive CYP3A4 Substrates

Voxelotor increased the systemic exposure of midazolam (a sensitive CYP3A4 substrate). Avoid co-administration with sensitive CYP3A4 substrates with a narrow therapeutic index. If unavoidable, consider dose reduction of the CYP3A4 substrate(s).

Strong CYP3A4 Inhibitors or Fluconazole

Co-administration of strong CYP3A4 inhibitors or fluconazole may increase voxelotor plasma concentrations and may lead to increased toxicity. Avoid co-administration of strong CYP3A4 inhibitors or fluconazole. Decrease Oxbryta dosage if unavoidable.

Strong or Moderate CYP3A4 Inducers

Co-administration of strong or moderate CYP3A4 inducers may decrease voxelotor plasma concentrations and may lead to reduced efficacy. Avoid co-administration of strong or moderate CYP3A4 inducers. Increase the Oxbryta dosage if unavoidable.

USE IN SPECIFIC POPULATIONS
Lactation

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. Reduce dose to 1,000 mg orally once daily for severe hepatic (Child Pugh C) impairment.

Please see Full Prescribing Information for more information about Oxbryta.

Results from a Phase I/II trial in patients with SCD treated with voxelotor vs placebo7,8

In a Phase I/II, randomized, double-blind, placebo-controlled study of voxelotor, patients with SCD (HbSS or HbSβ0 thalassemia), aged 18-60 years, were enrolled in 28-day cohorts (n=38) and 90-day cohorts (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.7

In this Phase I/II trial, fewer sickled RBCs were observed in patients with SCD treated with voxelotor vs placebo. A >70% decrease from baseline was observed in the proportion of sickle cells for patients with SCD treated with voxelotor vs placebo.7
Note: This study used lower doses of voxelotor than the FDA-approved Oxbryta dose of 1,500 mg daily.1

Representative blood smears from a Phase I/II trial7,8

Voxelotor-treated patient 1 with SCD (700 mg)7,8

Voxelotor-treated patient 1 with SCD (700 mg), Baseline.

Voxelotor, Baseline

Voxelotor-treated patient 1 with SCD (700 mg), Day 90.

Voxelotor, Day 90

Note: Results may not translate to clinical benefit

Voxelotor-treated patient 2 with SCD (700 mg)7

Voxelotor-treated patient 2 with SCD (700 mg), Baseline.

Voxelotor, Baseline

Voxelotor-treated patient 2 with SCD (700 mg), Day 90.

Voxelotor, Day 90

Note: Results may not translate to clinical benefit

Placebo-treated patient with SCD7,8

Placebo-treated patient 2 with SCD, Baseline.

Placebo, Baseline

Placebo-treated patient 2 with SCD, Day 90.

Placebo, Day 90

Note: Results may not translate to clinical benefit

In a Phase I/II trial, fewer sickled red blood cells (RBCs) were observed in patients with sickle cell disease (SCD) treated with voxelotor vs placebo7

Median % change from baseline in
RBC sickling at Day ≥907

Chart of median % change from baseline in RBC sickling at 90 days or more. Chart of median % change from baseline in RBC sickling at 90 days or more.

Note: Results may not translate to clinical benefit.
This study used lower doses of voxelotor than the FDA-approved Oxbryta dose of 1,500 mg daily.1

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 the 700 mg voxelotor and 900 mg voxelotor groups, respectively.7

HbSS = homozygous hemoglobin S; HbSβ0 thalassemia = hemoglobin sickle beta thalassemia

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