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. 2024 Jul 22;10(4):00151-2024.
doi: 10.1183/23120541.00151-2024. eCollection 2024 Jul.

Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics

James D Chalmers  1 , Pierre-Régis Burgel  2 , Charles L Daley  3 , Anthony De Soyza  4 , Charles S Haworth  5 , David Mauger  6 , Kevin Mange  7 , Ariel Teper  7 , Carlos Fernandez  7 , Dan Conroy  7 , Mark Metersky  8
Affiliations

Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics

James D Chalmers et al. ERJ Open Res. .

Abstract

Introduction: Brensocatib is an investigational, oral, reversible inhibitor of dipeptidyl peptidase-1 shown to prolong time to first exacerbation in adults with bronchiectasis. Outlined here are the clinical trial design, and baseline characteristics and treatment patterns of adult patients enrolled in the phase 3 ASPEN trial (NCT04594369).

Methods: The ASPEN trial is a global study enrolling patients with a clinical history consistent with bronchiectasis (cough, chronic sputum production and/or recurrent respiratory infections), diagnosis confirmed radiologically and ≥2 exacerbations in the prior 12 months. It was designed to evaluate the impact of two brensocatib doses (10 mg and 25 mg) on exacerbation rate over a 52-week treatment period versus placebo. Comprehensive clinical data, including demographics, disease severity, lung function, Pseudomonas aeruginosa status and quality of life, were collected at baseline.

Results: 1682 adults from 35 countries were randomised from December 2020 to March 2023. Mean age was 61.3 years and 64.7% were female. ∼70% had moderate-to-severe Bronchiectasis Severity Index (BSI) scores, 29.3% had ≥3 exacerbations in the prior 12 months and 35.7% were positive for P. aeruginosa. Mean BSI scores were highest in Australia/New Zealand (8.3) and lowest in Latin America (5.9). Overall, the most common aetiology was idiopathic (58.4%). In P. aeruginosa-positive versus P. aeruginosa-negative patients, lung function was lower, with greater long-term macrolide (21.5% versus 14.0%) and inhaled corticosteroid use (63.5% versus 53.9%). There was wide regional variation in long-term antibiotic use in patients with bronchiectasis and P. aeruginosa.

Discussion: ASPEN baseline characteristics and treatment profiles were representative of a global bronchiectasis population.

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Conflict of interest statement

Conflict of interest: J.D. Chalmers reports receiving grants and personal fees from AstraZeneca, Boehringer Ingelheim, GSK, Zambon and Insmed Incorporated, a grant from Gilead, and personal fees from Novartis and Chiesi. Conflict of interest: He is an Associate Editor of this journal. P-R. Burgel reports grants from Vertex and GSK, outside the submitted work. P-R. Burgel also reports clinical trials: acting as main investigator and advisory activity for AstraZeneca, Chiesi, GSK, Insmed Incorporated, MSD, Viatris, Vertex and Zambon. P-R. Burgel reports substantial financial contributions to the budget of an institution he is responsible for from GSK, Vertex, Association Vaincre la Mucoviscidose, Société Française de la Mucoviscidose and Filière MUCO-CFTR. Conflict of interest: C.L. Daley reports grant support, advisory board fees and consulting fees from Insmed Incorporated; grant support from AN2 Therapeutics, Bugworks, Paratek Pharmaceuticals and Juvabis; advisory board work with AN2 Therapeutics, AstraZeneca, Cepheid, Hyfe, MannKind, Matinas Biopharma, NobHill, Spero Therapeutics and Zambon; consulting with Genentech and Pfizer; and data monitoring committee work with Otsuka Pharmaceutical, Eli Lilly and Company, and the Bill and Melinda Gates Foundation. Conflict of interest: A. De Soyza reports grants and fees from AstraZeneca, Boehringer Ingelheim, Bayer, Chiesi, Gilead Sciences, GSK, Insmed Incorporated and Zambon. Conflict of interest: C.S. Haworth reports receiving consultancy/speaker fees from 30 Technology, CSL Behring, Chiesi, Insmed Incorporated, Janssen, LifeArc, Meiji, Mylan, Novartis, Pneumagen, Shinogi, Teva, Vertex and Zambon. Conflict of interest: D. Mauger reports grants from NHLBI and drugs for NIH-funded clinical trials from Genentech, GSK, OM Pharma and Sanofi-Regeneron. Conflict of interest: Conflict of interest: K. Mange, A. Teper, C. Fernandez and D. Conroy are employees of and shareholders in Insmed Incorporated. Conflict of interest: M. Metersky reports receiving consulting fees from AN2 Therapeutics, Boehringer Ingelheim, Insmed Incorporated, Renovion, Tactile Inc. and Zambon. Conflict of interest: J.D. Chalmers, P-R. Burgel, C.L. Daley, A. De Soyza, C.S. Haworth, D. Mauger and M. Metersky served as members of the ASPEN trial steering committee. J.D. Chalmers, P-R. Burgel, C.L. Daley, A. De Soyza, C.S. Haworth and M. Metersky were investigators in the ASPEN trial.

Figures

FIGURE 1
FIGURE 1
Study design. EOS: end of study; EOT: end of treatment.
FIGURE 2
FIGURE 2
Severity of bronchiectasis in the 12 months prior to baseline across regions. Proportion of patients with mild (BSI ≤4), moderate (BSI 5–8) or severe (BSI ≥9) BSI scores across regions. Regions are ordered by the proportion of patients with severe bronchiectasis according to BSI score, from highest on the left. BSI: Bronchiectasis Severity Index.
FIGURE 3
FIGURE 3
Aetiologies of bronchiectasis provided as overall and by region. a) Aetiologies of bronchiectasis provided for the ASPEN cohort. b) Aetiologies of bronchiectasis provided by region. Regions are ordered by idiopathic aetiology, from highest on the left.
FIGURE 4
FIGURE 4
Respiratory and non-respiratory comorbidities in the full ASPEN cohort and respiratory comorbidities by region. a) Respiratory and non-respiratory comorbidities in the full ASPEN cohort. Data are presented as n (%). b) Respiratory comorbidities by region. Regions are ordered by comorbid asthma, from highest on the left.
FIGURE 5
FIGURE 5
Demographics, characteristics, and long-term antibiotic use stratified by Pseudomonas aeruginosa positivity at baseline. a) Demographics and characteristics of patients with a positive sputum culture for P. aeruginosa at baseline. b) Long-term antibiotic use in patients with a positive sputum culture for P. aeruginosa at baseline. Regions are ordered by long-term use, from highest on the left. BD: bronchodilator; FEV1: forced expiratory volume in 1 s; ICS: inhaled corticosteroids.
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