SCD medical experts discuss Oxbryta and appropriate patient cases

Henry, Age 50, Male With SCD Genotype HbSβ0-thalassemia

Dr. Santosh L. Saraf discusses Henry who has an Hb level of 6.5 g/dL and has had 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 Dr. Santosh Saraf. I am an adult hematologist that cares for people with sickle cell disease. Welcome to this video, where we will discuss a hypothetical patient case, Henry.

We’re going to discuss whether Oxbryta may be appropriate for Henry, who’s a 50-year-old, African American man with hemoglobin S/beta-0 thalassemia sickle cell disease. He was a consultant traveling each week until a year ago. He has developed red cell antibodies, limiting his ability to get red cell transfusions.

In the past year, he has had three vaso-occlusive crises and two episodes of acute chest syndrome. More recently, he was prescribed an ACE inhibitor for his diagnosis of proteinuria. These recent events—vaso-occlusive crises, episodes of acute chest syndrome, and his diagnosis of proteinuria— are signaling that there is evidence that Henry may be experiencing organ damage.

Of note, about 5 years ago, Henry discontinued hydroxyurea because he wasn’t able to adhere to the frequent lab monitoring requirements.

Now, let’s look at his labs.

With a hemoglobin of 6.5 g/dL and elevated indirect bilirubin at 6.5 mg/dL and reticulocytes at 10%,

Henry’s lab workup is showing that he has severe hemolytic anemia.

Henry also has evidence of mild renal insufficiency with creatinine of 1.2 mg/dL and macroalbuminuria, a complication often related to hemolytic anemia.

After reviewing this patient case, would Oxbryta be an appropriate treatment option for Henry?

In this case, yes, Henry may benefit from taking Oxbryta. First of all, his hemoglobin is 6.5 g/dL, showing that he has significant anemia to contend with. As demonstrated in the HOPE study, patients similar to Henry had improvements in their hemoglobin, which Henry may also experience.

As mentioned before, Henry is also hemolytic. Also demonstrated in the HOPE study, patients with markers of hemolysis experienced reductions in both the indirect bilirubin and percent reticulocyte count. Oxbryta may provide that same benefit to Henry.

And, Oxbryta may fit into his lifestyle because it doesn’t require frequent blood morning and is taken orally, one time a day.

To reiterate, yes, I do think it would be appropriate to have a discussion with Henry about the dosing, efficacy, and safety of Oxbryta. Now that we have discussed Henry, we can shift to discussing the clinical safety of Oxbryta.

This table illustrates the adverse reactions that were observed in at least 10% of patients and with a difference of more than 3% in the Oxbryta vs placebo arms at Week 24 or Week 72.

These reactions included headache, diarrhea, abdominal pain, nausea, arthralgia, fatigue, rash, pyrexia, and back pain.

Serious adverse reactions that occurred in 3% of patients receiving 1,500 mg of Oxbryta included headache, drug hypersensitivity, and pulmonary embolism, occurring in one patient each at 24 weeks. No new events occurred after 24 weeks.

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 through Weeks 24 and 72.

Clinically relevant adverse reactions occurring in <10% of patients through Week 24 included drug hypersensitivity. No new events occurred after 24 weeks.

Please see important safety information at the end of this video.

I hope this review of Henry’s case helps you identify patients who may be appropriate for Oxbryta therapy in your patient population.

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.

Additional Videos
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Other Videos:

How Oxbryta Works

Listen to Dr. Nirmish Shah discuss the mechanism of action of Oxbryta, how it was designed to target HbS polymerization, and its proposed effect on red blood cell morphology.

For more information about the Oxbryta MOA, watch an additional video How oxbryta intervenes
Go to Video >>

Understanding the HOPE Trial

Dr. Santosh L. Saraf explores the Phase 3 HOPE trial, including the trial’s design, study endpoints, and baseline demographics. Go to Video >>

Efficacy & Safety of Oxbryta in the HOPE Trial

Dr. Alan Anderson describes the safety and efficacy results from the pivotal Phase 3 HOPE trial, including the impact of Oxbryta on anemia and hemolysis at 72 weeks. Go to Video >>

Dosing and Management of Your Patient on Oxbryta Therapy

Dr. Santosh L. Saraf reviews the convenient, once-daily oral dosing of Oxbryta, dose adjustment protocols utilized during the Phase 3 HOPE trial, and topics to discuss with patients when initiating Oxbryta therapy. Go to Video >>

Managing Side Effects During Oxbryta Treatment

While not necessary for all patients, dose modifications may be appropriate to help manage adverse reactions in some cases. Watch Dr. Alan Anderson describe the dose adjustment protocols utilized during the Phase 3 HOPE trial. Go to Video >>

Maria, Age 30, Female With SCD Genotype HbSS

Dr. Nirmish Shah discusses Maria who has an Hb level of 7.0 g/dL, has had 3 VOCs in the past year, and complains of increasing shortness of breath. Go to Video >>

Henry, Age 50, Male With SCD Genotype HbSβ0-thalassemia

Dr. Santosh L. Saraf discusses Henry who has an Hb level of 6.5 g/dL and has had 3 VOCs and 2 episodes of acute chest syndrome in the past year. Go to Video >>

Jamie, Age 12, Female With SCD Genotype HbSS

Dr. Alan Anderson discusses Jamie who has an Hb level of 7.5 g/dL and has had 1 VOC in the past year. Go to Video >>

Gabriel, Age 14, Male With SCD Genotype HbSS

Dr. Alan Anderson discusses Gabriel who has an Hb level of 6.0 g/dL, has had 3 VOCs in the past year, has established microalbuminuria, and complains of yellowing eyes. Go to Video >>

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