Insmed Incorporated reported data from eight presentations across three of its pillars—ARIKAYCE® (amikacin liposome inhalation suspension), brensocatib, and treprostinil palmitil inhalation powder (TPIP)—at the American Thoracic Society (ATS) 2023 International Conference in Washington, D.C. Summaries of these presentations follow: Poster: Outcomes of Patients With Bronchiectasis by Disease Severity: Subgroup Analysis From the Brensocatib WILLOW Study. This subgroup analysis of the phase 2 WILLOW study (a randomized, double-blind, placebo-controlled trial of brensocatib in adults with NCFBE) compared patient characteristics and outcomes, as determined by the Bronchiectasis Severity Index (BSI), in mild (=4), moderate (5–8), and severe (=9) bronchiectasis subgroups. At baseline, mean (standard deviation [SD]) BSI score in all patients was 8.3 (4.4).

Compared with placebo, brensocatib 10 mg and 25 mg (pooled data) reduced the risk of exacerbations across BSI subgroups during the study: In the mild subgroup: 41.2% of placebo and 13.9% of brensocatib patients had =1 exacerbation. In the moderate subgroup: 36.1% of placebo and 28.3% of brensocatib patients had =1 exacerbation. In the severe subgroup: 64.7% of placebo and 43.8% of brensocatib patients had =1 exacerbation.

Across all subgroups, compared with placebo, brensocatib was also associated with numerical reductions in rate of lung function decline. Both doses of brensocatib were well-tolerated. The most frequent AEs were headache, cough and sputum increased.

No major differences were seen across BSI subgroups. Between-group statistical comparisons were not possible because this was a post hoc analysis. Effects should be interpreted with caution because the size of some patient subgroups was small.

Mini Symposium: Long-term Hospitalization Burden Among Patients With Chronic Obstructive Pulmonary Disease With Possible Diagnostic Delays of Nontuberculous Mycobacterial Lung Disease. This retrospective cohort study used US Medicare claims (2006–2017) to assess the association between possible diagnostic delay of nontuberculous mycobacterial (NTM) lung disease and hospitalization burden among patients with chronic obstructive pulmonary disease (COPD) over a five-year period. The study identified 2,122 patients with COPD who were predicted to have NTM lung disease and received a subsequent NTM lung disease diagnosis.

These patients were grouped by the possible diagnostic delay (time from predicted NTM lung disease onset to date of NTM lung disease diagnosis): <2 years (early diagnosis), 2–3 years (intermediate diagnosis), and >3 years (late diagnosis). Patients who were diagnosed earlier showed a decrease in hospitalizations over the 5-year follow-up. Possible NTM lung disease diagnostic delay was found among a substantial proportion of patients with COPD, especially among those with more severe COPD and other respiratory comorbidities.

By the 5th year following the predicted NTM lung disease onset, hospitalization burden was highest in the late-diagnosis group: the late-diagnosis group was 2.1 times (95% CI, 1.6–2.7) more likely to experience all cause hospitalizations and 3.1 times (95% CI, 2.3–4.2) more likely to experience respiratory-related hospitalizations compared with the early-diagnosis group, despite controlling for confounding factors such as patient characteristics, comorbidities, and COPD severity. Study authors concluded that early NTM lung disease diagnosis may be associated with reduced longer-term hospitalization burden. Poster: The Dipeptidyl Peptidase-1 Inhibitor Brensocatib Reduces Airway Azurocidin-1 Levels in Bronchiectasis.

In this post-hoc analysis from the WILLOW study, researchers sought to measure the effect of brensocatib on azurocidin-1 (AZU1), an inflammatory mediator that is structurally related to neutrophil elastase but lacks protease activity. Sputum samples of patients enrolled in the trial were assessed at Day 1, Day 29, Day 169, and Day 197 (29 days following cessation of brensocatib treatment). Measurements of AZU1 concentration in sputum by ELISA showed: At Day 1, median sputum AZU1 levels, µg/mL (95% CI) were comparable across groups: brensocatib 10 mg, 80.26 (57.59, 182.8); brensocatib 25 mg, 122.7 (73.89, 198.1); and placebo, 137.5 (74.91, 258.5).

By Day 29, 51/134 (38%) in the combined brensocatib group compared with 5/86 (7%) in the placebo group had undetectable AZU1 (P < 0.001). This significant effect on AZU1 was maintained over the entire duration of the treatment period with levels returning to pre-treatment levels 29 days after brensocatib was stopped. These findings suggest a novel effect of brensocatib on the multifunctional inflammatory mediator AZU1.

The role of AZU1 in the pathophysiology of bronchiectasis warrants further investigation. Poster: Association of Baseline and Subsequent Bronchiectasis Exacerbations in Patients From the US Bronchiectasis and NTM Research Registry (BRR). This retrospective cohort study utilized data from patients enrolled in the US Bronchiectasis and Nontuberculous Mycobacteria (NTM) Research Registry (BRR) to explore the association between the number of bronchiectasis exacerbations at baseline and follow-up over 4 years.

Analyses of 520 patients were conducted at 3 time points in 2-year intervals: baseline (retrospective period of 2 years before enrollment), follow-up window 1 (years 1–2 after enrollment), and follow-up window 2 (years 3–4 after enrollment). Patients were categorized according to their baseline exacerbation status: 0 exacerbations or =1 exacerbation.  Compared with patients with no exacerbations at baseline, patients with prior exacerbations had significantly more exacerbations in years 1–2 (60% vs. 71%, P < 0.01) and years 3–4 (53% vs.

75%, P<0.0001). Prior bronchiectasis exacerbations at baseline increased the odds of bronchiectasis exacerbations in the first 2 years by 1.5 times (95% CI, 1.1–2.3) and in the subsequent 4 years by 2.4 times (95% CI, 1.6–3.5). These findings suggest that prevention or improved control of bronchiectasis exacerbations is a potential unmet need in patients with bronchiectasis.