Insmed Incorporated announced that additional positive results from the ASPEN study, a global, randomized, double-blind, placebo-controlled Phase 3 study to assess the efficacy, safety, and tolerability of brensocatib in patients with non-cystic fibrosis bronchiectasis, will be presented on July 4, 2024, at the 7th World Bronchiectasis Conference (WBC) in Dundee, Scotland. As previously announced, the ASPEN study met its primary endpoint, with both dosage strengths of brensocatib achieving statistical and clinical significance for the reduction in the annualized rate of pulmonary exacerbations (PEs) versus placebo over the 52-week treatment period. The annualized rate of exacerbations was 1.015 for the brensocatib 10 mg group, 1.036 for the brensocatib 25 mg group, and 1.286 for placebo, representing a 21.1% risk reduction from placebo for the brensocatib 10 mg group (p=0.0019) and a 19.4% risk reduction for the 25 mg group (p=0.0046).

Both dosage strengths of brensocatib also met several secondary endpoints, including significantly prolonging the time to first exacerbation and significantly increasing the odds of remaining exacerbation-free over the treatment period. The study assessed change in lung function, as measured by change from baseline in post-bronchodilator forced expiratory volume over one second (FEV1) at Week 52, a key secondary endpoint. Patients treated with brensocatib 25 mg demonstrated significantly less FEV1 decline, preserving more lung function as compared to placebo (LS mean change of 38 mL, p=0.0054).

Patients in the placebo arm lost on average 62 mL of FEV1 in one year. In addition, new data will be presented at WBC measuring the change from baseline in post-bronchodilator forced vital capacity (FVC) at Week 52, another measure of lung function and an exploratory endpoint in the study. Patients treated with brensocatib 25 mg showed nominally significantly less decline in FVC compared to placebo (LS mean change of 75 mL, p<0.0001).

Patients in both dosage groups of brensocatib experienced numerical improvements in change from baseline in the Quality of Life-Bronchiectasis (QOL-B) Respiratory Symptom Domain Score, with the brensocatib 25 mg dose group demonstrating a nominally significant improvement of 3.8 points versus placebo (p=0.0004). Improvements in patient reported QOL-B Respiratory Symptom Domain Score were seen as early as 4 weeks in both brensocatib arms. New data will also be presented at WBC on the change in average daily bronchiectasis exacerbation and symptom tool (BEST) score, an exploratory endpoint, which is a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations. Patients treated with brensocatib 25 mg showed a nominally significant 1-point decrease in BEST score compared to placebo.

Brensocatib was well-tolerated in the study and demonstrated a favorable safety profile. Treatment-emergent adverse events (TEAEs) occurring in at least 5.0% of patients treated with either dose of brensocatib and more frequently than in placebo were COVID-19 (15.8%, 20.9%, 15.8%), nasopharyngitis (7.7%, 6.3%, 7.6%), cough (7.0%, 6.1%, 6.4%), and headache (6.7%, 8.5%, and 6.9%) for brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively. Insmed plans to file a New Drug Application with the U.S. Food and Drug Administration for brensocatib in patients with bronchiectasis in the fourth quarter of 2024.

Pending regulatory approvals, Insmed anticipates a U.S. launch for brensocatib in mid-2025 followed by launches in Europe and Japan in the first half of 2026. If approved, brensocatib would be the first approved treatment for patients with bronchiectasis as well as the first approved dipeptidyl peptidase 1 (DPP1) inhibitor?a new mechanism of action with the potential to address a range of neutrophil-mediated diseases.