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Proven to significantly reduce exacerbation risk in bronchiectasis1,2

ASPEN study design

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The ASPEN study was an international, multicenter, randomized, double-blind, parallel-group, placebo-controlled Phase 3 clinical trial. Patients were 12 to 85 years of age (41 adolescents and 1680 adults) and received 1 of 2 doses of BRINSUPRI (10 mg: n=583; 25 mg: n=575) or placebo (n=563), administered orally once daily for 52 weeks.1,2

Patients in all arms were permitted to continue using their existing concomitant therapy.2,3

Exacerbations

PRIMARY ENDPOINT

BRINSUPRI is proven to reduce the risk of bronchiectasis exacerbations1,2,a

BRINSUPRI 10 mg
21.1%
reduction in exacerbation risk over 52 weeks

Rate ratio vs placebo (95% Cl): 0.79 (0.68-0.92); P=0.004.b

BRINSUPRI 25 mg
19.4%
reduction in exacerbation risk over 52 weeks

Rate ratio vs placebo (95% Cl): 0.81 (0.69-0.94); P=0.005.b

BRINSUPRI demonstrated a significant reduction in exacerbation risk over 52 weeks

A line graph comparing the cumulative mean number of exacerbations over 52 weeks between BRINSUPRI 25 mg (N=575), BRINSUPRI 10 mg (N=583), and placebo (N=563). The placebo group shows a higher risk of exacerbations compared to the BRINSUPRI 10 mg and the BRINSUPRI 25 mg group. The text highlights a 21.1% reduction in exacerbation risk over 52 weeks for BRINSUPRI 10 mg and a 19.4% reduction in exacerbation risk over 52 weeks for BRINSUPRI 25 mg.
aAnnualized rate.1
bP value was adjusted for multiplicity.2

Annualized exacerbation rate: BRINSUPRI 10 mg: 1.02, BRINSUPRI 25 mg: 1.04, placebo: 1.29.

Pulmonary exacerbations were defined as a worsening of ≥3 major symptoms over 48 hours resulting in a physician’s decision to prescribe systemic antibiotics.1

SECONDARY ENDPOINT

BRINSUPRI prolonged the time to first exacerbation1,2,4

BRINSUPRI 10 mg
12-week
median delay vs placebo

Hazard ratio vs placebo (95% CI): 0.81 (0.70-0.95); P=0.02.c

BRINSUPRI 25 mg
14-week
median delay vs placebo

Hazard ratio vs placebo (95% CI): 0.83 (0.70-0.97); P=0.04.c

Time to patients’ first exacerbation in the study

A line graph showing the time to a patient’s first exacerbation over 52 weeks for BRINSUPRI 10 mg (N=583), BRINSUPRI 25 mg (N=575), and placebo (N=563). The y-axis represents the proportion of patients with no pulmonary exacerbation, starting at 1.0 and decreasing over time. The BRINSUPRI 10 mg group and the BRINSUPRI 25 mg group have a higher proportion of patients without exacerbation compared to the placebo group at Week 52, indicating a delay in the time to first exacerbation with BRINSUPRI treatment.
cP value was adjusted for multiplicity.2

Time to first exacerbation (median weeks): BRINSUPRI 10 mg: 49.0, BRINSUPRI 25 mg: 50.7, placebo: 36.7.

SECONDARY ENDPOINT

Severe pulmonary exacerbations with BRINSUPRI vs placebo1,2

Pulmonary exacerbations were considered severe if they required treatment with IV antibacterial drugs and/or resulted in hospitalization.

BRINSUPRI 10 mg(N=583)

BRINSUPRI 25 mg(N=575)

Placebo(N=563)

Annualized rate of severe exacerbations
0.14
0.14
0.19
Rate ratio (95% CI)
0.74 (0.51-1.09)
0.74 (0.52-1.06)
–

These results were not statistically significant.

Lung function

SECONDARY ENDPOINT

BRINSUPRI 25 mg significantly reduced lung function decline at Week 521,2

Placebo: Patients taking placebo in the trial had a 62-mL mean decline from baseline in post-BD FEV1 at Week 52

BRINSUPRI 10 mg
19%
less decline in post-BD FEV1 vs placebo at Week 52

Difference vs placebo (95% CI): 11 mL (-14 to 37); P=0.38.e

Results were not statistically significant.

BRINSUPRI 25 mg
61%
less decline in post-BD FEV1 vs placebo at Week 52

Difference vs placebo (95% CI): 38 mL (11-65); P=0.04.e

Mean change from baseline in post-BD FEV1 at Week 52

A bar chart showing the mean change from baseline in post bronchodilator (post-BD) FEV₁ (forced expiratory volume in 1 second) at Week 52 for BRINSUPRI 10 mg (N=583), BRINSUPRI 25 mg (N=575), and placebo (N=563). The y-axis represents the least squares (LS) mean change in post-BD FEV₁ in milliliters. The BRINSUPRI 10 mg group (-50 mL) and BRINSUPRI 25 mg group (-24 mL) show a smaller decline in FEV₁ compared to the placebo group (-62 mL) at 52 weeks
eP value was adjusted for multiplicity.2

See the safety profile

BD=bronchodilator; CI=confidence interval; FEV1=forced expiratory volume in 1 second; IV=intravenous; LS=least squares.

Important Safety Information and Indication

WARNINGS AND PRECAUTIONS

Dermatologic Adverse Reactions
Treatment with BRINSUPRI is associated with an increase in dermatologic adverse reactions, including rash, dry skin, and hyperkeratosis. Monitor patients for development of new rashes or skin conditions and refer patients to a dermatologist for evaluation of new dermatologic findings.

Gingival and Periodontal Adverse Reactions
Treatment with BRINSUPRI is associated with an increase in gingival and periodontal adverse reactions. Refer patients to dental care services for regular dental checkups while taking BRINSUPRI. Advise patients to perform routine dental hygiene.

Live Attenuated Vaccines
It is unknown whether administration of live attenuated vaccines during BRINSUPRI treatment will affect the safety or effectiveness of these vaccines. The use of live attenuated vaccines should be avoided in patients receiving BRINSUPRI.

ADVERSE REACTIONS

The most common adverse reactions ≥2% in the ASPEN trial included upper respiratory tract infection, headache, rash, dry skin, hyperkeratosis, and hypertension. The safety profile for adult patients with NCFB in WILLOW was generally similar to ASPEN, except for a higher incidence of gingival and periodontal adverse reactions.

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 >3X upper limit of normal (ULN) was 0%, 1.2%, and 0.9%; the incidence of AST >3X ULN was 0.2%, 0.3%, and 0.5%; and the incidence of alkaline phosphatase >1.5X 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.

USE IN SPECIFIC POPULATIONS

Pregnancy: There are no clinical data on the use of BRINSUPRI in pregnant women.

Lactation: There is no information regarding the presence of BRINSUPRI and/or its metabolite(s) in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BRINSUPRI and any potential adverse effects on the breastfed child from BRINSUPRI or from the underlying maternal condition.

Pediatric use: The safety and effectiveness of BRINSUPRI for the treatment of NCFB have been established in pediatric patients aged 12 years and older. 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.

INDICATION

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

Please see full Prescribing Information.

Important Safety Information and Indication

WARNINGS AND PRECAUTIONS

Dermatologic Adverse Reactions
Treatment with BRINSUPRI is associated with an increase in dermatologic adverse reactions, including rash, dry skin, and hyperkeratosis. Monitor patients for development of new rashes or skin conditions and refer patients to a dermatologist for evaluation of new dermatologic findings.

Gingival and Periodontal Adverse Reactions
Treatment with BRINSUPRI is associated with an increase in gingival and periodontal adverse reactions. Refer patients to dental care services for regular dental checkups while taking BRINSUPRI. Advise patients to perform routine dental hygiene.

Live Attenuated Vaccines
It is unknown whether administration of live attenuated vaccines during BRINSUPRI treatment will affect the safety or effectiveness of these vaccines. The use of live attenuated vaccines should be avoided in patients receiving BRINSUPRI.

ADVERSE REACTIONS

The most common adverse reactions ≥2% in the ASPEN trial included upper respiratory tract infection, headache, rash, dry skin, hyperkeratosis, and hypertension. The safety profile for adult patients with NCFB in WILLOW was generally similar to ASPEN, except for a higher incidence of gingival and periodontal adverse reactions.

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 >3X upper limit of normal (ULN) was 0%, 1.2%, and 0.9%; the incidence of AST >3X ULN was 0.2%, 0.3%, and 0.5%; and the incidence of alkaline phosphatase >1.5X 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.

USE IN SPECIFIC POPULATIONS

Pregnancy: There are no clinical data on the use of BRINSUPRI in pregnant women.

Lactation: There is no information regarding the presence of BRINSUPRI and/or its metabolite(s) in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BRINSUPRI and any potential adverse effects on the breastfed child from BRINSUPRI or from the underlying maternal condition.

Pediatric use: The safety and effectiveness of BRINSUPRI for the treatment of NCFB have been established in pediatric patients aged 12 years and older. 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.

INDICATION

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

Please see full Prescribing Information.