SCD medical experts discuss Oxbryta and appropriate patient cases

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.

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. Nirmish Shah. And I’m a hematologist and director of a sickle cell transition program where my practice and research focus on treating both pediatric and adult patients with sickle cell disease.

Welcome to this video, where we’ll discuss a hypothetical patient case, Maria.

Maria is a 30-year-old Hispanic female with sickle cell disease genotype SS. She is quite busy with her two children and full-time work at a bank.

Maria has reported that over the past 2 months, she has been experiencing an increased shortness of breath. The workup included having an echocardiogram, which did show that she had an elevated TRV, or a tricuspid regurgitant jet velocity, of over 3 m/s. They followed up appropriately with a right heart catheterization and confirmed the diagnosis of pulmonary hypertension. In addition to that, Maria has had two blood transfusions and three vaso-occlusive crises in the past year.

She is on maximum tolerated dose of hydroxyurea. And she’s been titrated and is taking this as directed. In addition to her hydroxyurea, Maria’s also taking folic acid.

Now, Maria’s labs show that her hemoglobin is 7.0 g/dL. Her electrophoresis shows that her hemoglobin F is at 15%, a very good response to hydroxyurea, with a mean corpuscular volume of

110. Her white blood cell count shows that she’s just a little myelosuppressed with hydroxyurea, which is, again, a good response, an indication that we’re pushing her to be a maximum tolerated dose. Her white blood cell count is at 6,000. Her absolute neutrophil count is at 2,500.

But her reticulocyte count is at 12%. And her absolute retic count is at 371,000. Her total bilirubin and indirect bilirubins are still elevated, at 8 and 7.5 mg/dL, respectively. So Maria still has a fair amount of hemolysis despite maximum tolerated dose treatment with hydroxyurea.

So, would Maria, be a candidate for Oxbryta?

Yes, I think Maria may benefit from taking Oxbryta for three main reasons.

First, her sickle cell genotype is SS, which was one of the eligible genotypes in the HOPE study. Second, I also think that she may be a good candidate for Oxbryta because her hemoglobin is 7.0 g/dL while on maximum tolerated dose of hydroxyurea. This shows that Maria needs an additional intervention to get her anemia under control.

In the HOPE study, eligible patients, similar to Maria, who were on a stable dose of hydroxyurea for at least 90 days were allowed to stay on hydroxyurea throughout the study. And the results showed that Oxbryta provided an additional benefit on top of hydroxyurea.

And, finally, based on her elevated reticulocyte count 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 indirect bilirubin and percent retic count.

Considering these three reasons, I think it would be appropriate to have a discussion with Maria about the convenient, once-daily oral dosing, efficacy, and safety of Oxbryta.

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 observed in at least 10% of patients with a difference of more than 3% in the Oxbryta vs placebo arms at Week 24 or Week 72.

The 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 as well as at 72 weeks.

Clinically relevant adverse reactions occurred 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 the video. I hope this review of Maria’s case helps you identify appropriate patients 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%) 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
Show All Videos

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 >>

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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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