SCD medical experts discuss Oxbryta and appropriate patient cases

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.

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 Dr. Alan Anderson, and I’m the medical director of a comprehensive lifespan sickle cell disease program and a practicing hematologist. And I’m here to talk about a hypothetical patient case.

And that patient is Jamie, who is a 12- year-old African-American female with sickle cell disease genotype type SS.

Jamie likes to play soccer.

Her relevant past medical history includes that she’s had one VOC in the past year. She is currently on the maximum tolerated dose of hydroxyurea and she is 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.

You can see that she’s had a response from hydroxyurea by looking at her hemoglobin F at 20%, and her elevated MCV at 115. Her white blood cell count at 5,500/µL and ANC of 2,000, further show 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% and her absolute retic count is at 250,000/µL. Her total bilirubin and indirect bilirubin are 4.5 and 4 mg/dL, respectively.

So, the question becomes, would Jamie be a good candidate for Oxbryta?

Yes. I think Jamie may be a good candidate for Oxbryta.

Jamie’s age and SS genotype were both studied in the HOPE study, giving me confidence that Oxbryta was studied in patients that were similar to her.

I also think that she’d be a good candidate for Oxbryta, because her hemoglobin is 7.5 g/dL despite being on the maximum tolerated dose of hydroxyurea. This shows that Jamie needs an additional intervention to get her anemia under control.

In the HOPE study, eligible patients, similar to Jamie, who were on stable doses of hydroxyurea for at least 90 days were allowed to stay on hydroxyurea throughout the study. The results showed that Oxbryta increased hemoglobin levels, providing an additional benefit on top of hydroxyurea.

Finally, based on her elevated reticulocyte and indirect bilirubin, we know she is experiencing a fair amount of hemolysis.

In the phase 3 HOPE study, Oxbryta significantly reduced hemolysis as demonstrated by significant decreases to the patients’ level of indirect bilirubin and percent reticulocyte count.

Considering that patients similar to Jamie have been studied on Oxbryta and its efficacy improving anemia and hemolysis, I do feel confident about having the discussion about adding Oxbryta to Jamie’s treatment plan with her and her caregivers.

And with that in mind, here is a detailed overview of Oxbryta’s clinical safety that came out of the phase 3 HOPE trial.

This table illustrates the adverse reactions that were seen in at least 10% of patients and with a difference of more than 3% in the Oxbryta vs placebo arms at Week 24 or 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 Jamie’s case helps you identify patients that 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.

(≥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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