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 and Phase 2a HOPE-KIDS 1 trials, and topics to discuss with patients when initiating Oxbryta therapy.

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. Santosh Saraf. I’m an adult hematologist that cares for approximately 150 adults with sickle cell disease.

Welcome to this video, where we will discuss Oxbryta’s dosing and management considerations for the treatment of sickle cell disease.

There are 2 formulations of Oxbryta—Oxbryta tablets and Oxbryta tablets for oral suspension. Oxbryta is taken as a convenient once-daily oral dose. If your patient misses a dose or does not take the entire dose, they take the next dose on the following day. The tablets can be taken with or without food, but should not be cut, crushed, or chewed. The tablets for oral suspension should not be swallowed whole, cut, crushed, or chewed. And importantly, Oxbryta can be taken with or without hydroxyurea, and does not require laboratory monitoring.

The recommended daily dose of Oxbryta in patients 12 years and older is 1,500 milligrams, which can be taken as three 500-milligram tablets.

The recommended daily dose in patients 4 to less than 12 years depends on the patient’s weight. Those who weigh 40 kilograms or more should receive 1,500 milligrams as either three 500-milligram tablets or five 300-milligram tablets for oral suspension.

Patients who weigh 20 to less than 40 kilograms should receive 900 milligrams as three 300-milligram tablets for oral suspension.

And lastly, those who weigh 10 to less than 20 kilograms should receive 600 milligrams as two 300-milligram tablets for oral suspension.

The minimum recommended volume of clear drink needed for the Oxbryta tablets for oral suspension depends on the desired dose. For instance, if you are preparing a 600-milligram dose, or 2 tablets, then the minimum recommended volume is 2 teaspoons, or 10 milliliters. If you are preparing a 900-milligram dose, or 3 tablets, then the minimum recommended volume is 3 teaspoons, or 15 milliliters.

Immediately before administration, the tablets should be dispersed in room temperature clear liquid, such as drinking water or clear soda, before swallowing.

After the tablets start to disintegrate, swirl the contents of the cup until the tablets are dispersed, wait 1 to 5 minutes, swirl the contents of the cup again, and then orally administer the contents of the cup. Please note that the tablets will not completely dissolve; there will still be some small tablet clumps in the mixture. Any residue left in the cup should be resuspended in more clear drink and administered. Repeat this process until no tablet residue is left in the cup. Do not swallow whole, cut, crush, chew the tablets for oral suspension.

Please see Instructions for Use for full information on administration of Oxbryta tablets for oral suspension. For patients with mild or moderate hepatic impairment, no dose adjustment is needed.

However, the daily dose should be reduced in patients with severe hepatic impairment, defined as Child Pugh C. Patients aged 12 years and older should receive a reduced dose of 1,000 milligrams, as two 500-milligram tablets.

The recommended reduced daily dose in patients 4 to less than 12 years with severe hepatic impairment depends on the patient’s weight. Those who weigh 40 kilograms or more should receive 1,000 milligrams as two 500 milligram-tablets. Alternatively, they can receive 900 milligrams as three 300-milligram tablets for oral suspension.

Those who weigh 20 to less than 40 kilograms should receive 600 milligrams as two 300-milligram tablets for oral suspension…

And those who weigh 10 to less than 20 kilograms should receive 300 milligrams as one 300-milligram tablet for oral suspension.

Avoid the concomitant use of strong or moderate CYP3A4 inducers with Oxbryta. If concomitant use of strong or moderate CYP3A4 inducers is unavoidable, then adjust the dose accordingly.

With concomitant use of strong CYP3A4 inducers, patients aged 12 years and older should receive an increased Oxbryta dose of 2,500 milligrams, as five 500-milligram tablets.

The recommended increased daily dose in patients 4 to less than 12 years depends on the patient’s weight. Those who weigh 40 kilograms or more should receive 2,500 milligrams as five 500-milligram tablets. Alternatively, they can receive 2,400 milligrams as eight 300-milligram tablets for oral suspension.

Patients who weigh 20 to less than 40 kilograms should receive 1,500 milligrams as five 300-milligram tablets for oral suspension…

And those who weigh 10 to less than 20 kilograms should receive 900 milligrams as three 300-milligram tablets for oral suspension.

With concomitant use of moderate CYP3A4 inducers, patients 12 years and older should receive an increased Oxbryta dose of 2,000 milligrams, as four 500-milligram tablets.

The recommended increased daily dose in patients 4 to less than 12 years depends on the patient’s weight. Those who weigh 40 kilograms or more should receive 2,000 milligrams as four 500-milligram tablets. Alternatively, they can receive 2,100 milligrams as seven 300-milligram tablets for oral suspension.

Patients who weigh 20 to less than 40 kilograms should receive 1,200 milligrams as four 300-milligram tablets for oral suspension.

And those who weigh 10 to less than 20 kilograms should receive 900 milligrams as three 300-milligram tablets for oral suspension.

Dose modifications may be warranted to manage adverse events.

Throughout the entirety of the HOPE trial, 48% of adult and pediatric patients 12 years of age and older who 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 2 patients who received Oxbryta 1,500 milligrams included diarrhea and rash.

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

5% of patients permanently discontinued therapy due to an adverse reaction (Grades 1-4).

In the Phase 3 HOPE Trial, there were no discontinuations due to diarrhea, headache, rash, fatigue, arthralgia, or pyrexia.

Most diarrhea events reported were mild and self-limiting with the median time to onset being 15 days and the 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.

For patients who receive weight-based dosing with Oxbryta tablets for oral suspension, let them and their caregiver know that they can disperse the tablets in a clear drink, such as water or clear soda that tastes good to the patient.

Patients are encouraged 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.

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.

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 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 >>

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. 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 >>

Max, Age 6, Male with SCD Genotype HbSS

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

Dr. Alan Anderson discusses Tiana who has an Hb level of 7.9 g/dL and has had 2 VOCs in the past year. Go to Video >>

Get the latest information about Oxbryta delivered to your inbox