SCD medical experts discuss Oxbryta and appropriate patient cases

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.

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 patients with sickle cell disease, and I’d like to talk to you about Oxbryta’s dosing and management considerations for the treatment of sickle cell disease.

Oxbryta is taken as a convenient once-daily oral dose. If your patient misses a dose, they take the next dose on the following day.

It’s given as three pills, totaling 1,500 mg/day, without the need for dose- 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, and does not require laboratory monitoring.

For dose adjustments in patients with severe hepatic impairment, defined as 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 the concomitant use of strong or moderate CYP3A4 inducers, strong CYP3A4 inhibitors, or fluconazole with Oxbryta.

If concomitant use of a strong or moderate CYP3A4 inducer, a strong CYP3A4 inhibitor or fluconazole is unavoidable, then 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.

Dose modifications may be warranted to manage adverse events. 41% of patients at Week 24 and 48% of patients at Week 72 received Oxbryta required a dose modification, as either a dose reduction or interruption.

The most frequent adverse reactions requiring dosage interruption occurring in more than 1 patient who received Oxbryta 1,500 mg included diarrhea, headache, rash, and vomiting.

In the HOPE Trial patients needed a temporary modification based on physician discretion or adverse reaction severity could be lowered to 1,200 mg/day, which was a reductions of 1 pill in the HOPE trial based on the clinical formulation at the time, until the event subsided, and patients could return to 1,500 mg/day.

During the first 24 weeks, 5% of patients permanently discontinued therapy due to a treatment-related adverse reaction, with no additional discontinuations through Week 72.

There were no discontinuations due to diarrhea, headache, rash, fatigue, arthralgia, or pyrexia.

Most diarrhea events reported were mild and self-limiting. Median time to onset was 15 days, and median time from onset to resolution was 30 days.

Patients experiencing a Grade 1 or 2 rash were allowed oral antihistamines and/or topical steroids.

There are several key topics you should discuss with your patients when initiating Oxbryta therapy. Convey the importance of treating anemia and hemolysis. Describe how Oxbryta works, and show them the blood smear images in the patient brochure so they can get a real sense of Oxbryta’s impact, and how it can improve anemia and hemolysis. Set the patient’s expectations regarding potential side effects, and dose modifications you could utilize should those side effects occur. Share that Oxbryta needs to be taken continuously to maintain its effect.

Please also ask your patient to communicate openly about their treatment experience within a month. Emphasize Oxbryta’s convenience as a once-daily oral dose. And finally, be sure to address any concerns or questions they may have.

Thank you very much for listening to this presentation. I hope this information helps you manage your patients with sickle cell disease on Oxbryta. Please see important safety information at the end of this video.

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
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 >>

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 >>

Get the latest information about Oxbryta delivered to your inbox