Broad Immunomodulatory Effects of the Dipeptidyl Peptidase-1 Inhibitor Brensocatib in Bronchiectasis: Data from the Phase 2, Double-Blind, Placebo-controlled WILLOW Trial

Rationale: In the WILLOW (Assessment of INS1007 in Participants with Non-Cystic Fibrosis Bronchiectasis) trial, the dipeptidyl peptidase-1 inhibitor brensocatib reduced neutrophil serine protease activity and prolonged time to first exacerbation in patients with bronchiectasis. Objectives: We hypothesized that by reducing neutrophil serine proteases, brensocatib would affect antimicrobial peptides, mucins, and cytokines throughout the inflammatory cascade. Methods: The WILLOW trial was a phase 2 randomized trial of brensocatib (10 and 25 mg) versus placebo. Sputum was collected at baseline, Week 4, Week 24 (end of treatment), and Week 28 (4 wk after treatment). The antimicrobial peptides secretory leukoproteinase inhibitor (SLPI) and

• Johnson, E. D.
• Long, M. B.
• Perea, L.
• Shih, V. H.
• Fernandez, C.
• Teper, A.
• Cipolla, D.
• McIntosh, E.
• Galloway, R.
• Eke, Z.
• Shuttleworth, M.
• Hull, R.
• Spinou, A.
• De Soyza, A.
• Ringshausen, F. C.
• Goeminne, P.
• Lorent, N.
• Haworth, C.
• Loebinger, M. R.
• Blasi, F.
• Shteinberg, M.
• Aliberti, S.
• Polverino, E.
• Sibila, O.
• Shoemark, A.
• Mange, K.
• Huang, J. T. J.
• Stobo, J.
• Chalmers, J. D.