Video resources with medical experts

Medical experts examine the many aspects of Oxbryta

Browse through the following videos to discover more about Oxbryta and its benefits.

How Oxbryta works

Listen to an expert discuss the mechanism of action for Oxbryta.

For more information about the Oxbryta MOA, watch an additional video here.

Indications and usage. Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older. This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Please see full prescribing information for Oxbryta by clicking below for more information.

Hello. I’m Nirmish Shah. I’m here to talk about the mechanism of action of Oxbryta.

What I want to show here is the pathophysiology. Hemoglobin S polymerization is the root cause of the issues that happen as a cascade of events in sickle cell disease. And it all starts with the polymerization itself. And you can see that the polymerization is the first step, which then leads to the red blood cell being in its sickle formation, and then finally leads to hemolysis and anemia. And hemolysis is important within sickle cell disease because hemolysis leads to activated neutrophils, activated platelets, a decrease in nitric oxide, which then leads to impaired vasodilation. All of this hemolysis, anemia and vaso-occlusion leads to endothelial cell damage, limitation in blood to going to where it needs to go, and tissue ischemia.

Oxbryta’s been designed specifically to intervene in this cascade. It actually goes to the root cause. If you were to look at a microscope and look at a patient’s blood when they’re not on Oxbryta, you would see a number of cells that would be sickling and undergoing that hemolysis. If you were to zoom in to that red blood cell, you’d get a better idea of really what’s happening. And what you would see is that those hemoglobin S molecules and the whole job of hemoglobin are going to deliver the oxygen, and the issue becomes once it delivers the oxygen and the oxygen’s been released those hemoglobin molecules start stacking on themselves, and that stacking on themselves is because of the conformation that, and the charges that are expressed when it delivers the oxygen, and the polymerization and the stacking hemoglobin stretches out that red blood cell. And that gives you that classic sickled formation.

Now, what does Oxbryta do? Oxbryta goes in and it inserts itself in some of those hemoglobin molecules, into those hemoglobin S molecules. And actually, in fact, about 20 to 30% of the hemoglobin molecules will take up and bind to Oxbryta. And by binding the Oxbryta, when the oxygen is delivered, as you can see, the Oxbryta is still holding onto the oxygen. And that’s important because then when it tries to polymerize, when it tries to stack on itself, you have those hemoglobin S molecules that are now protected from that polymerization. They don’t go into that polymerization morphology. Nonclinical studies suggest that Oxbryta may inhibit red blood cell sickling, improve deformability, as well as reduce whole blood viscosity. But oxygen can be released to tissue under low-oxygen conditions.

So, with that, I want to thank you very much for listening to this presentation. I hope this provides a thorough review of the mechanism of action of Oxbryta, and again, I appreciate your time. Thank you very much.

Important Safety Information and Indication

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older.

This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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 hemoglobin subtypes A, S, and F by HPLC. If precise quantitation of hemoglobin 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 out of 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 substrates.

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 Oxbryta by clicking below for more information.

Understanding the HOPE trial

Explore the Phase 3 HOPE trial, including trial design, studied endpoints, and baseline demographics.

Hello. My name is Santosh Saraf. We’ll be discussing the HOPE clinical trial design and baseline patient characteristics.

Oxbryta is indicated for the treatment of patients with sickle cell disease, including adults or pediatric patients 12 years or older. The indication is approved under accelerated approval based on the increase in hemoglobin concentration. Continued approval of this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

So the HOPE trial was a phase 3 study. It was a multicenter randomized double-blind placebo-controlled trial. The key inclusion criteria included an age between 12 and 65 years old with confirmed sickle cell disease having one to ten vaso-occlusive crises per year within the 12 months, and being on a stable dose of hydroxyurea for at least 90 days and a baseline hemoglobin concentration between 5.5 and 10.5 g/dL. The primary endpoint was the percentage of patients that achieved a hemoglobin improvement of 1 g or greater at week 24 of therapy. Key exclusion criteria included red cell transfusions within 60 days, erythropoietin use within 28 days, renal insufficiency, uncontrolled liver disease, pregnancy or lactation. The patients were randomized 1:1:1 to either placebo, Oxbryta 900 mg, or Oxbryta 1,500 mg/day. And patients were stratified by hydroxyurea use, age and geographic region.

The primary endpoint of the HOPE trial was the percentage of patients that achieved a 1 g improvement in their hemoglobin concentration at week 24 compared to the baseline values. Additional key secondary endpoints included the change in hemoglobin concentration at week 24 compared to baseline, and the changes in hemolytic markers, such as indirect bilirubin level and reticulocyte counts from week 24 compared to baseline values.

So baseline demographics for patients in the phase 3 HOPE trial were similarly balanced between the placebo arm and the Oxbryta 1,500 mg arm. And this included age, with a range of 12 to 64 years, female sex, hydroxyurea use, hemoglobin concentration, frequency of vaso-occlusive crises, and regions. For hemoglobin concentration, the range was between 5.9 and 10.8 g/dL in the study.

So as a continuation of the prior slide, additional baseline demographics that were balanced between the Oxbryta arm and the placebo arm included race or ethnicity and hemoglobin genotype. And these included hemoglobin SS genotype, hemoglobin SC genotype, hemoglobin S/beta-0 thalassemia genotype and hemoglobin S/beta+ thalassemia genotype.

Please see important safety information at the end of the video. I hope this provides a useful overview of the HOPE study design and baseline characteristics to provide context for the clinical trial results.

Important Safety Information and Indication

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older.

This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon

verification and description of clinical benefit in confirmatory trials.

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 hemoglobin subtypes A, S, and F by HPLC. If precise quantitation of hemoglobin 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 out of 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 substrates.

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 Oxbryta by clicking below for more information.

Efficacy and safety of Oxbryta

An expert examines and describes the efficacy results from the Phase 3 pivotal HOPE trial and reviews the safety profile of Oxbryta.

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older. This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CONTRAINDICATIONS

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

My name is Dr. Ahmar Zaidi. Welcome to this video, where we will discuss the efficacy and safety results from the HOPE trial.

The phase 3 HOPE trial was a multicenter randomized double-blind placebo-controlled trial with 274 enrolled patients. The key inclusion criteria were patients who were age 12 to 65 years old with confirmed sickle cell disease, baseline hemoglobin between 5 and a half and 10 and a half, and patients needed to have one VOC in the 12 months preceding enrollment. If they were on hydroxyurea therapy, they were required to be on stable doses of hydroxyurea in the 90 days preceding enrollment. The key exclusion criteria included individuals who would have any reason for their hemoglobin to be falsely increased. Those are patients who were on red blood cell transfusions or received red blood cell transfusions in the 60 days preceding enrollment, or patients who were receiving erythropoietin. Patients with renal insufficiency or uncontrolled liver disease were also excluded, as were individuals who were pregnant or lactating. These individuals were then randomized 1:1:1 to three arms, one being the 1,500 mg approved dose of Oxbryta, the second being a 900 mg dose of Oxbryta arm, and the final one being the placebo arm. Patients were enrolled on the trial after a 4-week screening period, and then underwent a treatment period of 72 weeks.

The primary endpoint assessment in these individuals was the percentage of patients who achieved a greater than 1 g/dL increase in their hemoglobin at week 24. The secondary endpoint assessments included the change in hemoglobin levels from baseline to week 24, and changes in the laboratory markers that are associated with hemolysis, specifically indirect bilirubin and reticulocyte count.

This graph shows the change from baseline hemoglobin at week 24 for the patients who completed 24 weeks of therapy. It was found that Oxbryta significantly increased hemoglobin levels in the phase 3 HOPE trial. In fact, 51% of patients who received the 1,500 mg dose of Oxbryta during this trial achieved the primary endpoint of a greater than 1 g/dL increase in their hemoglobin compared to 7% of patients in the placebo arm. 42% of patients receiving Oxbryta therapy achieved a greater than 1.5 g/dL increase in hemoglobin, compared to 3% in the placebo group. 27% of patients receiving Oxbryta therapy achieved a greater than 2 g/dL increase in hemoglobin compared to 1% in the placebo group.

A rapid and durable hemoglobin response with Oxbryta was seen in the phase 3 HOPE trial. Significant increases in hemoglobin were observed within 2 weeks of starting treatment with Oxbryta, and these increases were sustained over 24 weeks.

In patients already on background hydroxyurea therapy, Oxbryta provided an incremental 1 g/dL mean increase in hemoglobin levels on top of any background hydroxyurea benefit.

Oxbryta demonstrated consistent results across clinically relevant subgroups regardless of age, VOC history or hydroxyurea use.

The phase 3 HOPE trial also showed as a secondary endpoint a reduction in hemolytic markers. Specifically, we see a reduction in indirect bilirubin by almost 30%, and a reduction in percent reticulocyte count by almost 20%.

Oxbryta significantly reduced the number of sickle red blood cells in a phase 1/2 study. The graph shows a median change 25th/75th percentile from baseline in the percentage of sickled red blood cells in patients treated with placebo or Oxbryta at day 90. At day 90, there was a greater than 70% decrease from baseline in proportion of sickle cells for patients treated with Oxbryta.

In preclinical studies with SS sickle blood, Oxbryta reduced whole blood viscosity. The graph shows blood viscosity for oxygenated and deoxygenated AA and SS red blood cells, as well as deoxygenated SS red blood cells incubated with Oxbryta. Treatment with Oxbryta significantly decreased the viscosity of deoxygenated red blood cells so that it was similar to oxygenated red blood cells.

The most common adverse reactions for patients receiving Oxbryta were headache, diarrhea, abdominal pain, nausea, fatigue, rash and pyrexia.

Serious adverse reactions that occurred in 3% or three out of 88 patients receiving 1,500 mg of Oxbryta therapy were headache, drug hypersensitivity and pulmonary embolism, occurring in one patient each. The safety profile observed in pediatric patients between the ages of 12 and 17 was similar to adult patients enrolled in the phase 3 trial. 41% of patients, or 36 out of 88, who received Oxbryta therapy required a dose modification. 5%, or four out of 88 patients, permanently discontinued Oxbryta therapy. Most frequent adverse reactions requiring dosage interruption in more than one patient who received Oxbryta included diarrhea, headache, rash and vomiting. Patients needing a temporary modification based on physician discretion or adverse reaction severity could be lowered to 1,200 mg/day until the event subsided, and then patients could return to 1,500 mg/day. Clinically relevant adverse reactions occurring in less than 10% of patients included drug hypersensitivity.

The laboratory measures of erythropoietin levels are indirect measures of tissue oxygenation preservation. And while no formal statistical testing was conducted, and the interpretation of these data are limited, the finding that erythropoietin levels did not increase with Oxbryta treatment may suggest that there is no impairment of tissue oxygenation for Oxbryta. However, additional clinical studies need to be conducted to confirm that Oxbryta preserves tissue oxygenation.

Important Safety Information and Indication

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older.

This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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 hemoglobin subtypes A, S, and F by HPLC. If precise quantitation of hemoglobin 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 out of 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 substrates.

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 Oxbryta by clicking below for more information.

I hope this presentation provides a useful overview and may help you understand and discuss Oxbryta as a treatment option with your patients with sickle cell disease.

How to dose Oxbryta

Learn about how to dose Oxbryta, including how and when dose adjustments might be necessary.

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older. This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CONTRAINDICATIONS

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

Hello. My name is Santosh Saraf, and we'll be discussing the indications and the dosage of Oxbryta to treat patients with sickle cell disease.

Oxbryta can be given conveniently as a once-daily oral dosing. It's given once a day. If a dose is missed, you continue the dosing on the day following the missed dose. It's given as three pills, or 1,500 mg/day, without the need for titration. It can be taken with or without food, but it should not be cut, crushed or chewed. And importantly, it can be taken with or without hydroxyurea.

For dose adjustments in patients with severe hepatic impairment, defined by Child-Pugh C, the recommended daily dose is reduced to 1,000 mg, or two tablets per day. No dose adjustment is needed for patients with mild or moderate hepatic impairment.

Avoid concomitant use of medications that may affect the CYP3A4 system, so strong or moderate inducers or strong inhibitors, such as fluconazole, with Oxbryta. If concomitant use of a strong or moderate CYP3A4 inducer, a strong CYP3A4 inhibitor or fluconazole is unavoidable, then you need to adjust the dose as follows. With a strong CYP3A4 inhibitor or fluconazole, the dose of Oxbryta should be reduced to 1,000 mg, or two pills per day. If a strong or moderate CYP3A4 inducer is used with Oxbryta, the dose should be increased to 2,500 mg, or five tablets per day. For complete information on dosage and administration, please see the full prescribing information for Oxbryta.

Thank you very much for listening to this presentation, and I hope this information is useful so that you can consider Oxbryta for your patients with sickle cell disease.

Important Safety Information and Indication

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older.

This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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 hemoglobin subtypes A, S, and F by HPLC. If precise quantitation of hemoglobin 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 out of 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 substrates.

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 Oxbryta by clicking below for more information.

Patient profiles

See some examples of patients who might be appropriate for Oxbryta. Please note these are not actual patients.

Maria

A 30-year-old female with SCD genotype HbSS, with an Hb level of 6.5 g/dL and 3 VOCs in the past year.

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older. This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CONTRAINDICATIONS

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

Hello, I’m Nirmish Shah. Now, I’m here to discuss a patient case.

And, a theoretical patient case named Maria. Now, Maria is a 30-year-old. She’s a Hispanic female with sickle cell disease type SS, as her genotype. She works in a bank. She’s quite busy with -- as a mother of two children. Some relevant past medical history that’s included here in the case is that she has shortness of breath over the past 2 months, and the workup included having a cardiac ECHO, and that ECHO did show that she had a TRV, or a tricuspid regurgitant velocity jet of over 3 m/s. They followed that out appropriately with a right heart catheterization, and with that they confirmed the diagnosis of pulmonary hypertension. In addition to that, she’s had two blood transfusions in the past year, and she’s had three vaso-occlusive crises in the past year. Now, in regards to treatment, very appropriately, they have her on hydroxyurea. And she’s actually on maximum tolerated dose. She’s been titrated and taken this -- taking this as directed. And in addition to her hydroxyurea, she’s on folic acid.

So we look at her labs, and we see that her labs show that her hemoglobin is 6.5 g/dL. Her electrophoresis shows that her hemoglobin F is at 15%, a very good response, with an MCV of 110. Her white count showing that she’s a little bit myelosuppressed with hydroxyurea, which is, again, a good response, an indication that we’re really pushing her to be at maximum tolerated dose. Her white count’s at 6,000. ANC is at 2,500. But her retic count is at 12%. Her absolute retic count is 371. So she’s still got a fair amount of hemolysis. If you see there, her total bilirubin and indirect are still quite elevated, at 10 and 9.5, respectively.

So the question comes up for Maria, again, as a theoretical case, would she be a good candidate for Oxbryta? And I think she would be. I think she’d be a good candidate for Oxbryta, and I think the two things to really highlight here are, number one, her hemoglobin is 6.5 while on hydroxyurea. And number two, she has a good amount of hemolysis. Her retic count is elevated. Her bilirubin is elevated. And so I think the combination of these factors that you see in her labs really show that she probably would be a great candidate to have a good discussion about Oxbryta.

Now, the clinical safety of Oxbryta from the phase 3 is another aspect that we want to make sure that we highlight. The adverse reactions which occurred in over 10% of patients receiving Oxbryta and with a difference between the arms of over 3% are listed here. And those adverse reactions include headache, diarrhea, abdominal pain, nausea. And then finally, fatigue, rash, and pyrexia.

Now, serious adverse reactions occurred in 3 patients, 3 out of 88, which is 3% of the patients receiving the 1,500 mg of Oxbryta and that would be headache, drug hypersensitivity, and pulmonary embolism occurring in one patient each. The safety profiles observed in pediatric patients 12 to 17 treated with Oxbryta were similar in comparison to those in the adult subgroup. 41%, that would be 36 of the 88 patients who received Oxbryta required a dose modification. 5%, or 4 patients, permanently discontinued therapy due to an adverse reaction, and that would be Grades 1-4. And the most frequent adverse reactions requiring dose interruption occurring in more than 1 patient receiving this 1,500-mg dose were diarrhea, headache, rash, and vomiting. Patients needing a temporary modification based on physician’s discretion or adverse reaction severity were to have patients lowered to the 1,200-mg dose in that HOPE trial until that event subsided, which could be returned back to the 1,500-mg dose. Clinically relevant adverse reactions occurred in <10% of patients and included drug hypersensitivity.

So with that, I want to thank you for your time today. Please see the important safety information at the end of the video. Reviewing Maria’s case will hopefully help you identify patients in your practice that may be appropriate for Oxbryta, as well. Thank you, again.

Important Safety Information and Indication

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older.

This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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 hemoglobin subtypes A, S, and F by HPLC. If precise quantitation of hemoglobin species is required, chromatography should be performed when the patient is not receiving Oxbryta therapy.

DVERSE REACTIONS

Clinical Trials Experience

Serious adverse reactions occurred in 3% (3 out of 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 substrates.

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 Oxbryta by clicking below for more information.

Henry

A 40-year-old male with SCD genotype HbSβ0-thalassemia, with an Hb level of 7.0 g/dL, 3 VOCs, and 2 episodes of acute chest syndrome in the past year.

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older. This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CONTRAINDICATIONS

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

Hello, my name is Santosh Saraf. Welcome to this video, where we’re going to discuss a theoretical patient case, Henry.

So we’re going to discuss whether Oxbryta would be appropriate for Henry, who’s a 40-year-old gentleman with hemoglobin S/beta-0 thalassemia sickle cell disease. He used to work as a consultant with frequent traveling up until a year ago. He has developed red cell antibodies, limiting his ability to get red cell transfusions. In the past year, he had three vaso-occlusive crises and two episodes of acute chest syndrome. And he was on hydroxyurea in the past, but stopped about 5 years ago due to the frequent lab monitoring requirements.

On laboratory workup, Henry has severe hemolytic anemia with a hemoglobin of 7, with an elevated indirect bilirubin and reticulocyte count. He also has a low hemoglobin F percentage, and he has evidence of mild renal insufficiency, with a creatinine of 1.2, and macroalbuminuria, a complication often related to hemolytic anemia.

So would Oxbryta be appropriate for this patient, Henry? His sickle cell genotype is S/beta-0, which was one of the eligible genotypes for the HOPE study. His hemoglobin is 7, which is within the 5.5 to 10.5 hemoglobin range in the HOPE study. And he has elevated hemolytic markers. So in this case, Henry could have potential benefit from Oxbryta with an improvement in hemoglobin based on the HOPE trial studies. It doesn’t require frequent blood monitoring, and he has very high levels of hemolytic markers, and Oxbryta may help both improve the hemoglobin concentration and reduce the degree of hemolysis in Henry.

This table demonstrates the adverse reactions that were observed in more than 10% of patients and with a frequency greater than 3% in the Oxbryta vs placebo arm. These reactions included headache, diarrhea, abdominal pain, nausea, fatigue, rash, and pyrexia.

Serious adverse reactions that occurred in 3% (or 3 out of 88) of patients receiving Oxbryta 1,500 mg included headache, drug hypersensitivity, and pulmonary embolism occurring in one patient each. The safety profile observed in pediatric patients 12 to <17 years of age treated with Oxbryta was similar to that seen in adult patients. 41% (or 36 out of 88) of patients who received Oxbryta required a dose modification. 5% (or 4 out of 88) permanently discontinued therapy due to an adverse reaction (Grades 1-4). Most frequent adverse reactions requiring dose interruption occurring in more than 1 patient who received Oxbryta 1,500 mg included diarrhea, headache, rash, and vomiting. Patients needing a temporary modification based on physician discretion or adverse reaction severity could be lowered to 1,200 mg/day until the event subsided, and patients could return to 1,500 mg/day afterwards. Clinically relevant adverse reactions occurring in <10% of patients included drug hypersensitivity.

Please see important safety information at the end of this video. I hope this case of Henry helps you identify patients that might be appropriate for Oxbryta therapy in your patient population.

Important Safety Information and Indication

NDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older.

This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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 hemoglobin subtypes A, S, and F by HPLC. If precise quantitation of hemoglobin 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 out of 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 substrates.

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 Oxbryta by clicking below for more information.

Jamie

A 12-year-old female with SCD genotype HbSS, with an Hb level of 7.5 g/dL and 1 VOC in the past year.

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older. This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CONTRAINDICATIONS

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

Hello. I’m Nirmish Shah, and I’m here to talk about a patient case.

And that patient is Jamie, who is a 12-year-old. And as a theoretical case, we have that she’s an African-American female with sickle cell disease genotype type SS. She likes to play soccer. Her relevant past medical history includes that she’s had one VOC in the past year, and in regards to treatment, she’s on hydroxyurea, and importantly at maximum tolerated dose, and she’s taking folic acid.

Now, let’s look at her labs. You can see that her labs indicate that her hemoglobin is 7.5 g/dL, and that’s with her being on hydroxyurea. And you can see that she has a response from hydroxyurea by looking at the next two sets of labs here. Hemoglobin F at 14%, and her MCV at 115. So, I know she’s taking her hydroxyurea. Her white count at 5,500 and ANC at 2,750 show, again, that we have her titrated to a good dose. Now, the remainder of her labs indicate that she still has hemolysis. Her reticulocyte count is at 9%. Her absolute retic count is at 250,000. Her total bilirubin and indirect bilirubin are 4.5 and 4 mg/dL. So, she still has hemolysis and her anemia.

So, the question becomes for Jamie as a theoretical patient to consider, is this patient a good candidate for Oxbryta? And I think she would be a good candidate for Oxbryta. And it’s the two parts that I just mentioned. She’s anemic despite being on hydroxyurea, and she has ongoing hemolysis. So, I think the combination of those things make me consider the fact that I should probably be talking to Jamie and her caregivers about Oxbryta. And I think that she definitely has the potential to benefit based on what we just discussed.

Now, the clinical safety of Oxbryta from the phase 3 is another aspect that we want to make sure that we highlight. The adverse reactions which occurred in over 10% of patients receiving Oxbryta and with a difference between the arms of over 3% are listed here. And those adverse reactions include headache, diarrhea, abdominal pain, nausea. And then finally, fatigue, rash, and pyrexia.

Now, serious adverse reactions occurred in 3 patients, 3 out of 88, which is 3% of the patients receiving the 1,500 mg of Oxbryta and that would be headache, drug hypersensitivity, and pulmonary embolism occurring in one patient each. The safety profiles observed in pediatric patients 12 to 17 treated with Oxbryta were similar in comparison to those in the adult subgroup. 41%, that would be 36 of the 88 patients who received Oxbryta required a dose modification. 5%, or 4 patients, permanently discontinued therapy due to an adverse reaction, and that would be Grades 1-4. And the most frequent adverse reactions requiring dose interruption occurring in more than 1 patient receiving this 1,500-mg dose were diarrhea, headache, rash, and vomiting. Patients needing a temporary modification based on physician’s discretion or adverse reaction severity were to have patients lowered to the 1,200-mg dose in that HOPE trial until that event subsided, which could be returned back to the 1,500-mg dose. Clinically relevant adverse reactions occurred in <10% of patients and included drug hypersensitivity.

So with that, I want to thank you for your time today. Please see the important safety information at the end of the video. But I hope that this review of Jamie’s case will help you identify patients that are in your practice who may also be appropriate for Oxbryta. Thank you, again.

Important Safety Information and Indication

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older.

This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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 hemoglobin subtypes A, S, and F by HPLC. If precise quantitation of hemoglobin 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 out of 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 substrates.

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 Oxbryta by clicking below for more information.

Jason

An 18-year-old male with SCD genotype HbSC, with an Hb level of 10 g/dL and 2 VOCs in the past year.

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older. This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

CONTRAINDICATIONS

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

My name is Dr. Ahmar Zaidi. Today, we will discuss Jason a theoretical sickle cell disease patient who’s 18 years old and has hemoglobin SC disease. Jason will be going away to college 6 months from now, and his parents are starting to get concerned because of a transition to a new health care provider and having to go through the transition process. He has a history of two VOCs in the past year and has imaging findings that are consistent with avascular necrosis of the hip. Jason has been offered hydroxyurea therapy in the past but has declined it. He takes folic acid, and also pain medications as needed.

Jason’s hematologic parameters are as follows. He has a hemoglobin of 10 g/dL, a white blood cell count of 8,600, an absolute neutrophil count of 4,000, reticulocyte percentage count of 4, a platelet count of 150,000, an absolute reticulocyte count of 290,000, and a total bilirubin of 1.8, with an indirect component of 1.6.

I would think that Jason would be a good candidate for Oxbryta therapy, particularly in a patient who will be transitioning to an adult health care provider and will be going far away from home. This is certainly a patient I believe would be a good candidate for Oxbryta.

The most common adverse reactions for patients receiving Oxbryta were headache, diarrhea, abdominal pain, nausea, fatigue, rash, and pyrexia.

Serious adverse reactions that occurred in 3%, or three out of 88 patients, receiving 1,500 mg of Oxbryta therapy were headache, drug hypersensitivity, and pulmonary embolism, occurring in one patient each. The safety profile observed in pediatric patients between the ages of 12 and 17 was similar to adult patients enrolled in the phase 3 trial. 41% of patients, or 36 out of 88, who received Oxbryta therapy required a dose modification. 5%, or four out of 88 patients, permanently discontinued Oxbryta therapy. Most frequent adverse reactions requiring dosage interruption in more than one patient who received Oxbryta included diarrhea, headache, rash, and vomiting. Patients needing a temporary modification based on physician discretion or adverse reaction severity could be lowered to 1,200 mg/day until the event subsided, and then, patients could return to 1,500 mg/day. Clinically relevant adverse reactions occurring in less than 10% of patients included drug hypersensitivity.

Please see important safety information at the end of this video. Thank you very much for listening to this presentation, and I hope the review of Jason’s case will help you identify patients in your practice who may benefit from Oxbryta therapy.

Important Safety Information and Indication

INDICATIONS AND USAGE

Oxbryta is indicated for the treatment of sickle cell disease in adults and pediatric patients 12 years of age and older.

This indication is approved under accelerated approval based on increase in hemoglobin. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

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 hemoglobin subtypes A, S, and F by HPLC. If precise quantitation of hemoglobin 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 out of 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 substrates.

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 Oxbryta by clicking below for more information.

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