Hemoglobin S (HbS) polymerization is the root cause
of red blood cell (RBC) sickling in sickle cell disease (SCD)^1-4

HbS molecules have a lower affinity for oxygen
When HbS releases oxygen, it can polymerize into long, rigid rods
These long, rigid rods deform the RBCs into sickled RBCs which, in turn, may contribute to other complications of SCD

HbS polymerization leads to RBC sickling and may also contribute to other SCD complications, including organ damage due to^1,5-7:

Anemia
Hemolysis
Hemolysis-mediated
endothelial dysfunction
Inflammation
Adhesion-mediated
vaso-occlusion

Potential contribution of HbS polymerization and RBC sickling to the complications of SCD.

Potential contribution of HbS polymerization and RBC sickling to the complications of SCD.

Anemia, hemolysis, and vaso-occlusive crises are hallmarks of SCD^6,8

Every patient with SCD experiences anemia and hemolysis⁸

Anemia and hemolysis may have an impact on organ damage and morbidity in
patients with SCD^1,9,10

Chronic organ damage:

Has emerged as a common cause of death in SCD^10-12
Progresses slowly in SCD and is associated with chronic anemia and hemolysis⁹

The extent of the association between chronic organ damage, anemia, and hemolysis is unknown.

Lower hemoglobin (Hb) levels and
anemia in SCD are associated with
increased risk of:

Cardiovascular events¹³
Renal damage^1,9
Multiple organ complications^1,9

Heart at risk.

Kidneys at risk.

Elevated markers of hemolysis in
SCD are associated with increased
risk of:

Stroke or silent cerebral infarct^10,14
Cardiovascular events¹³
Pulmonary hypertension^1,15,16

Brain at risk.

Lungs at risk.

Oxbryta is designed to specifically address the root cause of RBC sickling in SCD¹⁷

NEXT: How Oxbryta works

More

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

Contraindications

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.

Back to top

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

Contraindications

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

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.

Drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported in postmarketing experience with Oxbryta. Patients who develop a combination of skin rash, fever, peripheral eosinophilia, and internal systemic organ involvement (e.g., hepatic, renal, pulmonary) while receiving Oxbryta should undergo medical evaluation.

Advise patients of the signs and symptoms of severe hypersensitivity reactions, including DRESS. 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.

Adverse reactions

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 occurring in ≥10% of patients treated with 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.

Drug interactions

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 of Oxbryta with sensitive CYP3A4 substrates with a narrow therapeutic index. If concomitant use is unavoidable, consider dose reduction of the sensitive CYP3A4 substrate(s).

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 that breastfeeding is not recommended during treatment with 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.

References: 1. Oxbryta Full Prescribing Information. South San Francisco, CA: Global Blood Therapeutics, Inc.; 08/2023. 2. Vichinsky E, Hoppe CC, Ataga Kl, et al. A phase 3 randomized trial of voxelotor in sickle cell disease. N Engl J Med. 2019;381(6):509-519. doi:10.1056/NEJMoa1903212

References: 1. Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750-760. doi:10.1172/JCI89741 2. Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004;364(9442):1343-1360. doi:10.1016/S0140-6736(04)17192-4 3. Gordeuk VR, Castro OL, Machado RF. Pathophysiology and treatment of pulmonary hypertension in sickle cell disease. Blood. 2016;127(7):820-828. doi:10.1182/blood-2015-08-618561 4. Kapoor S, Little JA, Pecker LH. Advances in the treatment of sickle cell disease. Mayo Clin Proc. 2018;93(12):1810-1824. doi:10.1016/j.mayocp.2018.08.001 5. Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018-2031. doi:10.1016/S0140-6736(10)61029-X 6. Kato GJ, Piel FB, Reid CD, et al. Sickle cell disease. Nat Rev Dis Primers. 2018;4:18010. doi:10.1038/nrdp.2018.10 7. Caboot JB, Allen JL. Hypoxemia in sickle cell disease: significance and management. Paediatr Respir Rev. 2014;15(1):17-23. doi:10.1016/j.prrv.2013.12.004 8. Nader E, Romana M, Connes P. The red blood cell—inflammation vicious circle in sickle cell disease. Front Immunol. 2020;11:454. doi:10.3389/fimmu.2020.00454 9. Saraf S, Farooqui M, Infusino G, et al. Standard clinical practice underestimates the role and significance of erythropoietin deficiency in sickle cell disease. Br J Haematol. 2011;153(3):386-392. doi:10.1111/j.1365-2141.2010.08479.x 10. Ataga KI, Gordeuk VR, Agodoa I, Colby JA, Gittings K, Allen IE. Low hemoglobin increases risk for cerebrovascular disease, kidney disease, pulmonary vasculopathy, and mortality in sickle cell disease: a systematic literature review and meta-analysis. PLoS One. 2020;15(4):e0229959. doi:10.1371/journal.pone.0229959 11. Elmariah H, Garrett ME, De Castro LM, et al. Factors associated with survival in a contemporary adult sickle cell disease cohort. Am J Hematol. 2014;89(5):530-535. doi:10.1002/ajh.23683 12. Chaturvedi S, Ghafuri DL, Jordan N, Kassim A, Rodeghier M, DeBaun MR. Clustering of end-organ disease and earlier mortality in adults with sickle cell disease: a retrospective-prospective cohort study. Am J Hematol. 2018;93(9):1153-1160. doi: 10.1002/ajh.25202 13. Damy T, Bodez D, Habibi A, et al. Haematological determinants of cardiac involvement in adults with sickle cell disease. Eur Heart J. 2016;37(14):1158-1167. doi:10.1093/eurheartj/ehv555 14. Ford AL, Ragan DK, Fellah S, et al. Silent infarcts in sickle cell disease occur in the border zone region and are associated with low cerebral blood flow. Blood. 2018;132(16):1714-1723. doi:10.1182/blood-2018-04-841247 15. Gladwin MT, Kato GJ. Cardiopulmonary complications of sickle cell disease: role of nitric oxide and hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2005;51-57. doi:10.1182/asheducation-2005.1.51 16. Wood KC, Gladwin MT, Straub AC. Sickle cell disease: at the crossroads of pulmonary hypertension and diastolic heart failure. Heart. 2020;106(8):562-568. doi:10.1136/heartjnl-2019-314810 17. Oxbryta Full Prescribing Information. South San Francisco, CA: Global Blood Therapeutics, Inc.; 08/2023.

References: 1. Oxbryta Full Prescribing Information. South San Francisco, CA: Global Blood Therapeutics, Inc.; 08/2023. 2. Vichinsky E, Hoppe CC, Ataga Kl, et al. A phase 3 randomized trial of voxelotor in sickle cell disease. N Engl J Med. 2019;381(6):509-519. doi:10.1056/NEJMoa1903212 3. Howard J. Hemmaway CJ, Telfer P, et al. A phase 1/2 ascending dose study and open-label extension study of voxelotor in patients with sickle cell disease. Blood. 2019;133(17):1865-1875. doi:10.1182/blood-2018-08-868893 4. Data on file. Pfizer Inc.

References: 1. Oxbryta Full Prescribing Information. South San Francisco, CA: Global Blood Therapeutics, Inc.; 08/2023. 2. Vichinsky E, Hoppe CC, Ataga Kl, et al. A phase 3 randomized trial of voxelotor in sickle cell disease. N Engl J Med. 2019;381(6):509-519. doi:10.1056/NEJMoa1903212 3. Data on file. Pfizer Inc. 4. Howard J, Ataga KI, Brown RC, et al. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021;8(5):e323-e333. doi:10.1016/S2352-3026(21)00059-4 5. Study to evaluate the effect of GBT440 in pediatrics with sickle cell disease (HOPE Kids). ClinicalTrials.gov identifier: NCT02850406. Updated January 19, 2022. Accessed February 24, 2022. https://clinicaltrials.gov/ct2/show/NCT02850406

References: 1. Oxbryta Full Prescribing Information. South San Francisco, CA: Global Blood Therapeutics, Inc.; 08/2023. 2. Data on file. Pfizer Inc. 3. Howard J, Ataga KI, Brown RC, et al. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haemotol. 2021;8(5):e323-e333. doi:10.1016/S2352-3026(21)00059-4

Reference: 1. Oxbryta Full Prescribing Information. South San Francisco, CA: Global Blood Therapeutics, Inc.; 08/2023.