Drug Trials Snapshots: BRINSUPRI

BRINSUPRI (brensocatib) (Brin-SOO-pree) Insmed, Inc. Approval date: August 12, 2025 DRUG TRIALS SNAPSHOT SUMMARY: What is the drug for? BRINSUPRI is a dipeptidyl peptidase 1 (DPP1) inhibitor that is indicated for the treatment of non-cystic fibrosis bronchiectasis in adult and pediatric patients 12 years of age and older. Non-cystic fibrosis bronchiectasis (NCFB) is a chronic and progressive inflammatory lung condition that can lead to breathing complications and death. People with NCFB have recurrent flare-ups called pulmonary exacerbations (PEx). During a PEx, patients experience worsening respiratory symptoms, such as cough, increased sputum, and fatigue, and need antibiotics for treatment. Each time a PEx occurs, the lungs are damaged, and this damage worsens the airways over time. As NCFB progresses, patients have more trouble with breathing and more frequent infections that require treatment with long-term antibiotics, oxygen, physiotherapy, and other drugs (e.g. mucolytics) to loosen mucus. How is this drug used? BRINSUPRI is an oral tablet that is taken by mouth once daily. Who participated in the clinical trials? The FDA approved BRINSUPRI based on evidence from two clinical trials, ASPEN and WILLOW, that enrolled 1,936 adult and 41 adolescent patients with NCFB. ASPEN enrolled patients in 402 centers, and WILLOW enrolled patients in 101 centers. The trials were conducted in 38 countries (Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Denmark, Estonia, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Mexico, the Netherlands, New Zealand, Peru, Poland, Portugal, South Korea, Serbia, Singapore, Slovakia, Spain, Taiwan, Thailand, Turkey, the United Kingdom, and the United States) and included a total of 309 patients from the United States. Among the 1,977 enrolled patients, all of them were evaluated for efficacy (Intent-to-Treat population) and 1,974 patients were evaluated for safety. How were the trials designed? BRINSUPRI was evaluated in two clinical trials that evaluated the efficacy and safety of BRINSUPRI at 10 mg and 25 mg doses administered by mouth once daily over 52 weeks (ASPEN) and 24 weeks (WILLOW). ASPEN enrolled 1,680 adults and 41 adolescents with NCFB, and WILLOW enrolled 256 adults with NCFB. In both trials, subjects were randomized to receive BRINSUPRI 10 mg, BRINSUPRI 25 mg, or placebo. The primary efficacy endpoints of both trials assessed PEx, which were defined as a worsening of three or more major symptoms (e.g., cough, sputum volume or color or consistency, breathlessness, fatigue, and coughing up blood) over 48 hours that required treatment with antibiotics. DEMOGRAPHICS SNAPSHOT Figure 1 summarizes how many male and female patients were enrolled in the combined trials used to evaluate the efficacy of BRINSUPRI. Figure 1. Baseline Demographics by Sex, Intent-to-Treat Population Source: Adapted from FDA Review Figure 2 summarizes how many patients by race were enrolled in the combined trials used to evaluate the efficacy of BRINSUPRI. Figure 2. Baseline Demographics by Race, Intent-to-Treat Population Source: Adapted from FDA Review Figure 3 summarizes how many patients by age were enrolled in the combined trials used to evaluate the efficacy of BRINSUPRI. Figure 3. Baseline Demographics by Age, Intent-to-Treat Population Source: Adapted from FDA Review Figure 4 summarizes how many patients by ethnicity were enrolled in the combined trials used to evaluate the efficacy of BRINSUPRI. Figure 4. Baseline Demographics by Ethnicity, Intent-to-Treat Population Source: Adapted from FDA Review What are the benefits of this drug? In ASPEN, patients with NCFB aged 12 years and older taking BRINSUPRI 10 mg and 25 mg had a reduction of 21% and 19%, respectively, in the annualized rate of PEx compared to placebo. In WILLOW, patients with NCFB aged 18 years and older taking BRINSUPRI 10 mg and 25 mg had a longer time until their first PEx compared to placebo. Were there any differences in how well the drug worked in clinical trials among sex, race, and age? Sex: BRINSUPRI worked similarly in males and females. Race: The number of patients of races other than White was small; therefore, differences in how well BRINSUPRI worked among races could not be determined. Age: BRINSUPRI worked similarly in patients 12 to less than 18 years of age, 18 to less than 65 years of age, or at least 65 years of age. Ethnicity: BRINSUPRI worked similarly among different ethnicities (Hispanic or Latino and not Hispanic or Latino). What are the possible side effects? The most common side effects of BRINSUPRI included upper respiratory tract infections, headache, rash, dry skin, hyperkeratosis (skin thickening), and hypertension (high blood pressure). Less common side effects of BRINSUPRI include abnormal liver blood test results, alopecia (hair loss), and skin cancers. Some of these side effects occurred more often for patients taking the 25 mg dose than for those taking the 10 mg dose. BRINSUPRI may cause serious side effects including skin problems and dental problems. Tell your healthcare provider about any new skin symptoms. Your healthcare provider may send you to a dermatologist for a skin exam if needed. Because of the risk of dental problems, it is important to get regular dental checkups and to brush and clean your teeth as recommended by your dentist while taking BRINSUPRI. Tell your healthcare provider and contact your dentist if you have new gum or teeth symptoms. Were there any differences in side effects among sex, race and age? Sex: The occurrence of side effects was similar in males and females. Race: The number of patients of races other than White was small; therefore, differences in the occurrence of side effects by race could not be determined. Age: The occurrence of side effects was similar in patients 12 to less than 18 years of age, 18 to less than 65 years of age, or at least 65 years of age. Ethnicity: The occurrence of side effects was similar by ethnicity (Hispanic or Latino and not Hispanic or Latino). GLOSSARY CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments. COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested. EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial. PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo. SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups. PRESCRIBING INFORMATION