SCD medical experts discuss Oxbryta and appropriate patient cases

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 who cares for approximately 150 patients with sickle cell disease.

Welcome to this video, where we will discuss a hypothetical patient case, Henry.

We’re going to discuss whether Oxbryta may be appropriate for Henry, who’s a 50-year-old, African American man with hemoglobin S/beta-0 thalassemia sickle cell disease. He was a consultant traveling each week until a year ago.

He has developed red cell antibodies, limiting his ability to get red cell transfusions.

In the past year, he has had three vaso-occlusive crises and two episodes of acute chest syndrome. More recently, he was prescribed an ACE inhibitor for his diagnosis of proteinuria. These recent events—vaso-occlusive crises, episodes of acute chest syndrome, and his diagnosis of proteinuria—are signaling that there is evidence that Henry may be experiencing organ damage.

Of note, about 5 years ago, Henry discontinued hydroxyurea because he wasn’t able to adhere to the frequent lab monitoring requirements.

Now, let’s look at his labs.

With a hemoglobin of 6.5 grams per deciliter and elevated indirect bilirubin at 6.5 milligrams per deciliter and reticulocytes at 10%, Henry’s lab workup is showing that he has severe hemolytic anemia.

Henry also has evidence of mild renal insufficiency with creatinine of 1.2 milligrams per deciliter and macroalbuminuria, a complication often related to hemolytic anemia.

After reviewing this hypothetical patient case, would Oxbryta be an appropriate treatment option for Henry?

In this case, yes, Henry may benefit from taking Oxbryta.

First of all, his hemoglobin is 6.5 grams per deciliter, showing that he is severely anemic. As demonstrated in the HOPE study, patients similar to Henry had improvements in their hemoglobin, which Henry may also experience.

As mentioned before, Henry is also hemolytic. As demonstrated in the HOPE study, there were reductions in markers of hemolysis including both the indirect bilirubin and percent reticulocyte count. Oxbryta may provide that same benefit to Henry.

And, Oxbryta may fit into his lifestyle because it doesn’t require frequent blood monitoring and is taken orally, one time a day.

To reiterate, yes, I do think it would be appropriate to have a discussion with Henry about the dosing, efficacy, and safety of Oxbryta. Now that we have discussed Henry, we can shift to discussing the clinical safety of Oxbryta.

Here, we have the safety data 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).

Since our hypothetical patient case Henry is an adult, let’s focus on the adverse events from the adult and pediatric patients 12 years of age and older.

This table illustrates the adverse reactions that were seen in at least 10% of adult and pediatric patients 12 years of age and older, and with a difference of more than 3% in the Oxbryta vs placebo arms through Week 72 in the Phase 3 HOPE Trial.

These reactions included headache, diarrhea, abdominal pain, nausea, rash, and pyrexia.

Serious adverse reactions that occurred in 3% of patients receiving 1,500 milligrams of Oxbryta included headache, drug hypersensitivity, and pulmonary embolism, occurring in one patient each.

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

I hope this review of Henry’s case helps you identify patients that may be appropriate for Oxbryta therapy in your patient population. 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.