Brinsupri Drug Information

is indicated for the treatment of non-cystic fibrosis bronchiectasis (NCFB) in adult and pediatric patients 12 years of age and older. BRINSUPRI is a dipeptidyl peptidase 1 (DPP1) inhibitor indicated for the treatment of non-cystic fibrosis bronchiectasis in adult and pediatric patients 12 years of age and older.

Recommended Dosage

The recommended dosage of BRINSUPRI is as follows: 10 mg orally once daily with or without food or 25 mg orally once daily with or without food Missed Dose(s) Patients who miss a dose should take the next dose at their regular time the next day. Do not double the dose to make up for the missed dose.

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. The safety data below reflect the safety of BRINSUPRI in adult and pediatric patients aged 12 years and older with non-cystic fibrosis bronchiectasis (NCFB). A total of 1721 patients with NCFB were randomized in a double-blind, placebo-controlled clinical trial of 52 weeks duration (ASPEN). The safety of BRINSUPRI was based on data from 1719 adult and pediatric patients aged 12 years and older who received at least one dose of BRINSUPRI or placebo. A total of 1156 patients received at least one dose of BRINSUPRI 10 mg or 25 mg orally once daily.

Table 1 shows the adverse reactions occurring at an incidence of ≥2% and higher in BRINSUPRI-treated patients compared to placebo in the safety population from ASPEN. Table 1 Adverse Reactions with BRINSUPRI with an Incidence of ≥2% and More Common than Placebo in ASPEN Adverse Reaction Placebo (N=563) n (%) BRINSUPRI 10 mg QD (N=582) n (%) BRINSUPRI 25 mg QD (N=574) n (%) Upper respiratory tract infection Upper respiratory tract infection includes coronavirus infection, COVID-19, influenza, upper respiratory tract infection, viral infection, and viral upper respiratory tract infection. 141 157 169 Headache 39 39 49 Rash Rash includes rash, rash maculo-papular, rash pruritic, rash erythematous, dermatitis, and erythema. 22 25 35 Dry skin Dry skin includes dry skin, chapped lips, cheilitis, lip dry, skin exfoliation, skin fissures, xeroderma, and xerosis. 8 17 25 Hyperkeratosis Hyperkeratosis includes hyperkeratosis, palmoplantar keratoderma, and skin hypertrophy. 5 8 16 Hypertension 17 28 13 Adverse Reactions in WILLOW A total of 256 adult patients with NCFB were randomized in the 24-week, double-blind, placebo-controlled clinical trial (WILLOW). Of those randomized, 255 adult patients received BRINSUPRI 10 mg, BRINSUPRI 25 mg, or placebo, which consisted of 170 adults treated with at least one dose of BRINSUPRI 10 mg or 25 mg orally once daily. The safety profile for adult patients with NCFB in WILLOW was generally similar to ASPEN, with the exception of a higher incidence of gingival and periodontal adverse reactions. The incidence of gingival and periodontal adverse reactions in WILLOW among patients treated with BRINSUPRI 10 mg and 25 mg were 9.9% and 10.1%, respectively, compared to 2.4% in placebo-treated patients.

Less Common Adverse Reactions Liver Function Test Elevations In ASPEN, there was an increase from baseline in average ALT, AST, and alkaline phosphatase levels at all time points from Week 4 through Week 56 in both BRINSUPRI 10 mg and 25 mg arms compared to placebo. The incidence of ALT >3× upper limit of normal (ULN) was 0%, 1.2%, and 0.9%, in patients treated with placebo and BRINSUPRI 10 mg and 25 mg, respectively. The incidence of AST >3× ULN was 0.2%, 0.3%, and 0.5% in patients treated with placebo and BRINSUPRI 10 mg and 25 mg, respectively.

The incidence of alkaline phosphatase >1.5× ULN was 2.5%, 4.1%, and 4.0% in patients treated with placebo and BRINSUPRI 10 mg and 25 mg, respectively. Skin Cancers In ASPEN, the incidence of skin cancers among patients treated with BRINSUPRI 10 mg and 25 mg was 0.5% and 1.9%, respectively, compared to 1.1% in placebo-treated patients. Alopecia In ASPEN, the incidence of alopecia among patients treated with BRINSUPRI 10 mg and 25 mg was 1.5% and 1.6%, respectively, compared to 0.4% in placebo-treated patients.

Pregnancy Risk Summary There are no available data on BRINSUPRI use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal embryo fetal development (EFD) studies, oral administration of brensocatib to pregnant rats during organogenesis at maternal exposures 128 times the maximum recommended human dose (MRHD) on an AUC basis was associated with malformations. Oral administration of brensocatib to pregnant rabbits during organogenesis demonstrated no adverse developmental effects at doses that produced maternal exposures up to 20 times the MRHD. No adverse development effects were observed after oral administration of brensocatib to pregnant rats from the period of organogenesis through lactation at doses that produced maternal exposures 17 times the MRHD on an AUC basis (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In a rat fertility and EFD study, brensocatib was administered at oral doses of 3, 20, and 100 mg/kg/day to female rats 2 weeks prior to mating, during mating, and through organogenesis until gestation Day 16. The malformation of bent scapula was observed at a maternal dose of 100 mg/kg/day (128 times the MRHD on an AUC basis). There were no adverse findings at maternal oral doses of 20 mg/kg/day (42 times the MRHD on an AUC basis). In a rabbit EFD study, brensocatib was administered at oral doses of 5, 15, or 50 mg/kg/day from gestation Days 7 to 19, a period that covers implantation and major organogenesis.

Brensocatib was not associated with adverse effects on the fetus at maternal exposures up to 20 times the MRHD on an AUC basis. Maternal toxicity as indicated by reductions in body weight gain and food consumption was noted at maternal doses of 15 mg/kg/day and greater (greater than 5 times the MRHD on an AUC basis). In a pre- and postnatal development study, oral administration of brensocatib to pregnant rats at doses of 3, 9, or 20 mg/kg/day from gestation Day 6 through lactation Day 20 resulted in no adverse developmental effects in pups at maternal doses up to 20 mg/kg/day (17 times the MRHD on an AUC basis).

Pediatric Use The safety and effectiveness of BRINSUPRI for the treatment of NCFB have been established in pediatric patients aged 12 years and older. Use of BRINSUPRI for this indication is supported by evidence from an adequate and well-controlled trial (ASPEN), which enrolled 41 pediatric patients aged 12 years and older, and additional pharmacokinetic data in pediatric patients aged 12 to 17 years. Common adverse reactions in pediatric patients aged 12 years and older enrolled in ASPEN were consistent with those in adults . The safety and effectiveness of BRINSUPRI have not been established in pediatric patients younger than 12 years of age.

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