SCD medical experts discuss Oxbryta and appropriate patient cases

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.

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).

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.

Hello, my name is Dr. Alan Anderson. And I’m a pediatric hematologist who cares for 450 individuals with sickle cell disease.

Welcome to this video, where we will review the hypothetical patient, Gabriel.

Gabriel is a 14-year-old, Hispanic male with sickle cell disease genotype SS. While Gabriel spends his free time playing video games or watching TV, both of his parents have busy work schedules, which makes it challenging to bring him in for frequent medical appointments.

Gabriel has had three vaso-occlusive crises in the past year, he has established microalbuminuria, and yellowing of the eyes signaling that he has evidence of organ and vascular damage.

While he is showing signs of worsening symptoms, his family declines hydroxyurea as a treatment option for his sickle cell disease.

Gabriel’s labs show that he has hemolytic anemia with his hemoglobin at 6.0 grams per deciliter, his percent reticulocyte count at 14, and his indirect bilirubin at 5.5 milligrams per deciliter.

Other labs include his white blood cell count at 14,000 per microliter and his absolute neutrophil count at 9,000 per microliter. Also, his serum creatinine is 0.5 milligrams per deciliter and his estimated glomerular filtration rate is 145.

After considering this patient case, would Gabriel be a good candidate for Oxbryta?

Yes. I think Gabriel may benefit from taking Oxbryta.

First of all, Gabriel’s parents have busy work schedules, making it difficult to bring him in for frequent medical appointments. With Oxbryta, frequent laboratory monitoring is not required and has the added convenience of once-daily, oral dosing.

I also think he may benefit from taking Oxbryta to help raise his hemoglobin. Gabriel’s hemoglobin is 6 grams per deciliter, showing he is severely anemic. As demonstrated in the HOPE study, patients similar to Gabriel had improvements in their hemoglobin. The increase in hemoglobin was observed as early as 2 weeks after starting Oxbryta, and the increases were sustained over 24 and 72 weeks.

Gabriel is experiencing yellowing in his eyes.

In the HOPE study, patients experienced significant reductions in indirect bilirubin. Patients also experienced significant reductions in percent reticulocytes. Oxbryta may provide that same benefit to Gabriel.

Now that we have talked about Gabriel, we can shift to discussing the clinical safety of Oxbryta in the Phase 3 HOPE Trial.

Here, we have the safety data from the Phase 3 HOPE and Phase 2a HOPE-KIDS 1 trials…..

The safety profile observed in pediatric patients aged 12 to <17 years treated with Oxbryta was similar to that seen in adult patients.

The overall safety profile of Oxbryta tablets for oral suspension in pediatric patients 4 to <12 years was similar to that seen in adults and pediatric patients (≥12 years).

Since our hypothetical patient case Gabriel is 14 years old, let’s focus on the adverse events from the adults and pediatric patients 12 years of age and older.

This table illustrates the adverse reactions that were seen in at least 10% of adults and pediatric patients 12 years of age and older, and with a difference of more than 3% in the Oxbryta vs placebo arms through Week 72 in the Phase 3 HOPE Trial.

The reactions included headache, diarrhea, abdominal pain, nausea, rash, and pyrexia.

Serious adverse reactions that occurred in 3% of patients receiving 1,500 milligrams of Oxbryta included headache, drug hypersensitivity, and pulmonary embolism, occurring in one patient each.

Seventy-four patients received Oxbryta 1,500 milligrams once daily for ≥24 weeks, 65 patients for ≥48 weeks, and 63 patients completed the 72-week treatment period.

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

INDICATION AND IMPORTANT SAFETY INFORMATION

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.

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 (≥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.

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 with sensitive CYP3A4 substrates with a narrow therapeutic index. If unavoidable, consider dose reduction of the 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 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 by clicking below for more information about Oxbryta.

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How Oxbryta Works

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For more information about the Oxbryta MOA, watch an additional video How Oxbryta intervenes
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Understanding the HOPE and HOPE-KIDS 1 Trials

Dr. Santosh Saraf explores the Phase 3 HOPE trial, including the trial’s design, study endpoints, and baseline demographics, as well as the study design from the Phase 2a HOPE-KIDS 1 trial. Go to Video >>

Efficacy & Safety of Oxbryta in the HOPE and HOPE-KIDS 1 Trials

Dr. Santosh Saraf describes the safety and efficacy results from the pivotal Phase 3 HOPE trial and the Phase 2a HOPE-KIDS 1 trial. 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 and Phase 2a HOPE-KIDS 1 trials, 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 >>

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

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Jamie, Age 12, Female With SCD Genotype HbSS

Dr. Nirmish Shah 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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Dr. Nirmish Shah discusses Max who has an Hb level of 7.1 g/dL and has an acute chest syndrome (ACS) episode approximately once a year. Go to Video >>

Tiana, Age 8, Female with SCD Genotype HbSS

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