SCD medical experts discuss Oxbryta and appropriate patient cases

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.

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 over 450 individuals with sickle cell disease.

Welcome to this video. During this presentation I’d like to talk to you about how we managed side effects seen in patients in the HOPE and HOPE-KIDS 1 clinical trials. This information may help guide management of patients on Oxbryta in your clinical practice.

Let’s begin by looking at the clinical safety data of Oxbryta from the Phase 3 HOPE and Phase 2a HOPE-KIDS 1 trials.

The safety profile observed in pediatric patients 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).

The table on the left illustrates the most common adverse reactions that were observed in at least 10% of patients treated with Oxbryta 1,500 milligrams with a difference of more than 3% compared with placebo at Week 72 in the HOPE trial. These included headache, diarrhea, abdominal pain, nausea, rash, and pyrexia.

The serious adverse reactions that occurred in 3% (3/88) of patients receiving Oxbryta 1,500 milligrams included headache, drug hypersensitivity, and pulmonary embolism, occurring in 1 patient each.

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

The table on the right illustrates the adverse reactions that were observed in pediatric patients aged 4 to <12 years who received Oxbryta tablets for oral suspension in the HOPE-KIDS 1 trial. These reactions included pyrexia, vomiting, rash, abdominal pain, diarrhea, and headache.

There were no discontinuations of Oxbryta tablets for oral suspension related to vomiting, rash, abdominal pain, diarrhea, or headache.

While not needed for all patients, dose modification may be warranted to help 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 dose 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 the 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.

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

Thank you very much for listening to this presentation. I hope this information helps you manage side effects your patients may experience while 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.

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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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