6 ADVERSE REACTIONS
The following clinically significant adverse reaction is discussed in other sections of the labeling:
- Hypersensitivity Reactions [see Contraindications (4) and Warnings and Precautions (5.1)].
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adults and Pediatric Patients 12 Years and Older
The safety of OXBRYTA was evaluated in the HOPE trial based on data from 88 patients with SCD who received OXBRYTA 1,500 mg and 91 patients who received placebo orally once daily [see Clinical Studies (14.1)]. Seventy-four patients received OXBRYTA 1,500 mg once daily for ≥24 weeks, 65 patients for ≥48 weeks, and 63 patients completed the 72-week treatment period.
In patients who received OXBRYTA 1,500 mg once daily the median age was 24 years (range:12 to 59 years); 65% female; 66% Black or African American and 23% Arab/Middle Eastern; and 65% receiving hydroxyurea at baseline.
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.
Dosage modifications (dose reduction or dosing interruption) due to an adverse reaction occurred in 48% (42/88) of patients who received OXBRYTA. Most frequent adverse reactions requiring dosage modifications occurring in more than two patients who received OXBRYTA 1,500 mg included diarrhea and rash.
The safety profile observed in pediatric patients 12 to <17 years treated with OXBRYTA in the HOPE trial was similar to that seen in adult patients.
The most common adverse reactions occurring in ≥10% of patients treated with OXBRYTA 1,500 mg with a difference of >3% compared to placebo are summarized in Table 4.
| Adverse Reaction* | OXBRYTA 1,500 mg (N=88) | Placebo (N=91) |
|---|---|---|
| ||
| Headache | 32% | 25% |
| Diarrhea | 23% | 11% |
| Abdominal Pain† | 23% | 16% |
| Nausea | 19% | 10% |
| Rash‡ | 15% | 11% |
| Pyrexia | 15% | 8% |
Clinically relevant adverse reactions occurring in <10% of patients included:
- Drug hypersensitivity
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 [see Clinical Studies (14.2)]. 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.