Brinsupri (brensocatib) / Insmed, AstraZeneca - LARVOL DELTA

EFFECT OF BRENSOCATIB ON COMPUTED TOMOGRAPHY OUTCOMES IN PATIENTS WITH NON-CYSTIC FIBROSIS BRONCHIECTASIS: AN ANALYSIS OF THE ASPEN TRIAL (CHEST 2025) - P3 | "Both doses of brensocatib, particularly brensocatib 25mg, showed improvements in some CT endpoints vs placebo. These findings, together with improvements in lung function reported in the primary study, suggest that the impact brensocatib on inflammatory processes may result in structural lung changes. Further studies are needed to understand the implications of these findings."

Clinical • Late-breaking abstract • Bronchiectasis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

EFFICACY AND SAFETY OF BRENSOCATIB IN PATIENTS OF ASIAN RACE WITH NON-CYSTIC FIBROSIS BRONCHIECTASIS: A SUBGROUP ANALYSIS OF THE ASPEN TRIAL (CHEST 2025) - P3 | "Consistent with the overall study population, both brensocatib doses reduced the annualized exacerbation rate and lung function decline, and improved patient-reported symptoms vs placebo in Asian patients enrolled in ASPEN. CLINICAL IMPLICATIONS: Brensocatib is a selective, reversible DPP1 inhibitor that directly targets neutrophil-mediated inflammation. These results demonstrate that brensocatib has a positive impact in Asian patients with bronchiectasis, consistent with the general ASPEN population, despite differences in baseline characteristics, leading to further understanding of bronchiectasis treatment in this population."

Clinical • Bronchiectasis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • ELANE

EFFICACY AND SAFETY OF BRENSOCATIB IN PATIENTS WITH NONCYSTIC FIBROSIS BRONCHIECTASIS AND COMORBID COPD: A SUBGROUP ANALYSIS OF THE ASPEN TRIAL (CHEST 2025) - P3 | "Consistent with the overall study population, brensocatib reduced exacerbation rates regardless of comorbid COPD. Brensocatib 25mg reduced lung function decline in patients with and without comorbid COPD. CLINICAL IMPLICATIONS: Brensocatib is a selective, reversible DPP1 inhibitor that directly targets neutrophil-mediated inflammation."

Clinical • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • ELANE

EFFECTS OF BRENSOCATIB ON NEUTROPHIL SERINE PROTEASE LEVELS IN PATIENTS WITH NONCYSTIC FIBROSIS BRONCHIECTASIS: AN ANALYSIS OF THE ASPEN TRIAL (CHEST 2025) - P3 | "Pharmacodynamic analyses showed that, consistent with the phase 2 WILLOW trial, brensocatib treatment generally resulted in a dose-dependent reduction of NSP activity within 4 weeks. NSP activity was stably suppressed throughout the treatment period and increased toward baseline after 4 weeks off-treatment. Furthermore, brensocatib 25mg showed a more pronounced reduction of sputum NSP activity than the 10mg dose."

Clinical • Bronchiectasis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSG • ELANE

CHANGES IN SYMPTOM BURDEN DURING PULMONARY EXACERBATIONS IN PLACEBO-TREATED PATIENTS WITH NONCYSTIC FIBROSIS BRONCHIECTASIS: A POSTHOC ANALYSIS FROM THE ASPEN TRIAL (CHEST 2025) - P3 | "Brensocatib, an oral, selective, competitive, and reversible inhibitor of dipeptidyl peptidase 1, prevents activation of neutrophil serine proteases associated with bronchiectasis disease progression... Overall BEST and individual symptom diary scores were increased before and after onset of a PEx, regardless of severity; however, patients with severe PEx experienced a greater symptom burden and longer duration of PEx-related symptoms. Higher symptom burden during severe PEx was driven by breathlessness, fatigue, cough, and cold/flu symptoms. CLINICAL IMPLICATIONS: PEx-related symptoms in patients with bronchiectasis remain elevated for several weeks after peak PEx event, contributing to disease burden."

Clinical • Retrospective data • Bronchiectasis • Chronic Cough • Cough • Fatigue • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

THE EFFECT OF BRENSOCATIB VS PLACEBO ON SYMPTOM BURDEN IN PATIENTS WITH OR WITHOUT ON-STUDY PULMONARY EXACERBATIONS: A POSTHOC ANALYSIS FROM THE ASPEN TRIAL (CHEST 2025) - P3 | "Brensocatib 10mg and 25mg reduced symptom burden, regardless of PEx occurrence; the reductions were greatest in patients on 25mg and those without on-study PEx. Both brensocatib doses also reduced the symptom burden vs placebo during severe PEx events. CLINICAL IMPLICATIONS: Patient-reported symptom burden was lowest in patients without PEx and improved with doses of brensocatib regardless of PEx occurrence or severity, highlighting the importance of PEx prevention."

Clinical • Retrospective data • Bronchiectasis • Chronic Cough • Cough • Fatigue • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Recent Investigations in Pharmacotherapy for Bronchiectasis. (PubMed, Am J Respir Crit Care Med) - No abstract available

Journal • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Efficacy of Brensocatib in Patients with Eosinophilic Inflammation in Bronchiectasis: An Analysis of the ASPEN Trial (WBC 2025) - P3 | "Consistent with the overall study population, both brensocatib doses reduced the annualized rate of exacerbations, and brensocatib 25-mg also reduced lung function decline and nominally improved patient-reported outcomes regardless of high or low blood eosinophil counts at baseline."

Clinical • Bronchiectasis • Eosinophilia • Genetic Disorders • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • ELANE

Lung Function in Patients With Non-Cystic Fibrosis Bronchiectasis By Prespecified Subgroups in the Phase 3, Randomized, Double-Blind, Placebo-Controlled Aspen Trial (WBC 2025) - P3 | "Consistent with the results of the overall ASPEN trial population, brensocatib 25-mg reduced FEV 1 decline vs placebo for all subgroups analyzed. These results demonstrate that brensocatib has a positive impact on post-bronchodilator FEV 1 across all subgroups evaluated, an important observation in a heterogeneous disease like bronchiectasis. Previously presented at CHEST 2024."

Clinical • P3 data • Asthma • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Cough • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Profiling DPP-1 signalling networks underlying lung immune defence (WBC 2025) - "We identified that 30 mg/kg/day brensocatib significantly reduced DPP1 activity, along with a corresponding reduction in elastase activity in the murine lung. This establishment of DPP1 inhibition in brensocatib-treated vs drug vehicle-treated groups will enable us to proceed with enrichment-free N-terminomics to identify changes in global protein abundance and proteolytic cleavages mediated by DPP1."

Inflammation • Pulmonary Disease • Respiratory Diseases • CTSB • CTSK • ELANE • LGMN

Brensocatib Reduced Bronchiectasis Exacerbations, Improved Symptoms in Asian Patients (Respiratory Therapy) - "Brensocatib reduced the annualized exacerbation rate (rate ratio [95% CI] 10mg: 0.40 [0.23-0.67]; 25mg: 0.41 [0.24-0.70]), prolonged time to first exacerbation (hazard ratio [95% CI] 10mg: 0.45 [0.26-0.77], 25mg: 0.47 [0.27-0.82]), and increased the odds of remaining exacerbation-free (odds ratio [95% CI] 10mg: 3.29 [1.46-7.40]; 25mg: 3.19 [1.43-7.13]) vs placebo. Brensocatib reduced FEV1 decline (week 52 least squares mean (LSmean) difference in mL vs placebo [95% CI] 10mg: 18 [-27-63]; 25mg: 69 [24-114])....Further results will be shared at the CHEST Annual Meeting 2025..."

P3 data • Non‐Cystic Fibrosis Bronchiectasis

A Phase 3, randomized, double-blind, placebo-controlled trial of brensocatib in patients with non-cystic fibrosis bronchiectasis-the ASPEN trial (WBC 2024) - P3 | "The pivotal phase 3 ASPEN trial evaluating the efficacy and safety of brensocatib is the largest bronchiectasis global clinical trial program to date, enrolling over 1700 patients spanning 35 countries and 5 continents. Brensocatib is a first-in-class, selective, and reversible DPP1 inhibitor developed to directly target neutrophil-mediated inflammation, which may have the potential to improve clinical outcomes in patients with bronchiectasis. There are currently no indicated treatments for bronchiectasis approved by the FDA or EMA."

Clinical • P3 data • Bronchiectasis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • ELANE

LATE BREAKING BRONCHIECTASIS SCIENCE LECTURE 1 Brensocatib in patients with non-CF bronchiectasis-the ASPEN study (WBC 2024) - No abstract available

Clinical • Late-breaking abstract • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Neutrophil dysfunction in bronchiectasis: Pathophysiological insights and emerging targeted therapies. (PubMed, Multidiscip Respir Med) - "Key emerging therapies include DPP-1 inhibitors (e.g., brensocatib), CXCR2 antagonists, PI3K inhibitors, and NET-targeting therapies...Although targeting neutrophil dysfunction offers a promising avenue for advancing bronchiectasis care, balancing immunomodulation and infection control remains a challenge. The integration of novel therapies with biomarker-guided treatment and treatable trait approaches is essential to improve the outcomes of this complex disease."

Journal • Allergic Bronchopulmonary Aspergillosis • Bronchiectasis • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • ELANE

Insmed to Present Multiple Analyses from Phase 3 ASPEN Study at the American College of Chest Physicians Annual Meeting 2025 (PRNewswire) - "Presentations will feature new prespecified and post-hoc subgroup analyses from the Phase 3 ASPEN trial evaluating brensocatib in patients with non-cystic fibrosis bronchiectasis (NCFB)....Additional presentations feature new insights into treatment outcomes among patients with comorbid chronic obstructive pulmonary disease (COPD), clinical findings in Asian populations, and detailed assessments of symptom burden using the Bronchiectasis Exacerbation and Symptom Tool (BEST), both during and outside of pulmonary exacerbation events."

P3 data • Chronic Obstructive Pulmonary Disease • Immunology • Non‐Cystic Fibrosis Bronchiectasis

CHMP Recommends EU Approval of BRINSUPRI (brensocatib) for the Treatment of Non-Cystic Fibrosis Bronchiectasis (PRNewswire) - "The CHMP opinion is based on a comprehensive scientific evaluation of the marketing authorization application, including data from the Phase 3 ASPEN and Phase 2 WILLOW studies...RINSUPRI was reviewed under accelerated assessment by the EMA as it is deemed to be of major interest for public health and therapeutic innovation....The European Commission (EC) will review the CHMP opinion, with a final decision anticipated in the coming months."

CHMP • Non‐Cystic Fibrosis Bronchiectasis

Positioning Dipeptidyl Peptidase-1 Inhibitors in Bronchiectasis: No Drug Is an Island. (PubMed, Am J Respir Crit Care Med) - No abstract available

Journal • Bronchiectasis • Inflammation • Pulmonary Disease • Respiratory Diseases

Next-Generation Therapies for Hidradenitis Suppurativa: Recent FDA Approvals and a Look at Clinical Trial Landscape (EADV 2025) - "Over the past decade, numerous immunotherapies have been developed for a wide range of dermatologic conditions, including two recently FDA-approved treatments for HS within the last year (bimekizumab and secukinumab)2,3...Sonelokimab, another IL-17A/F inhibitor, is currently in a recruiting phase 3 trial...Other cytokine-targeting agents are lutikizumab (IL-1α/IL-1β inhibitor), spesolimab (anti-IL-36R), and anifrolumab (type I interferon receptor antagonist)...Agents targeting the JAK-STAT pathway include the JAK1 inhibitors povorcitinib, upadacitinib, and ruxolitinib, as well as deucravacitinib, a tyrosine kinase 2 inhibitor; all are currently under investigation for HS...Remibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, also showed promising results, with 72.7% of patients reaching the HiSCR endpoint at week 167. Brensocatib, a dipeptidyl-peptidase 1 inhibitor, is currently being evaluated in a recruiting phase 3 trial... The last decade has brought a wave..."

Clinical • Dermatology • Hidradenitis Suppurativa • Immunology • Inflammation • IFNAR2 • IL17A • IL1B • TYK2

NEJM- Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis, incl. discussion and QA (ERS 2025) - "Selected by NEJM as the first licensed therapy for bronchiectasis, this is a major advance"

P3 data • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Efficacy and safety of brensocatib in patients with non-cystic fibrosis bronchiectasis and Pseudomonas aeruginosa infection: Analysis of the ASPEN trial (ERS 2025) - P3 | "Adverse events (AE) were similar across tx arms; PsA + pts had more AEs. Consistent with overall results, regardless of PsA status, brensocatib showed benefits in PEx, lung function, and QOL-B RSS vs pbo."

Clinical • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Efficacy and safety of brensocatib in Japanese patients with non-cystic fibrosis bronchiectasis: Analysis of the ASPEN trial (ERS 2025) - P3 | "Adverse events were similar across groups. Consistent with the overall trial, brensocatib showed benefit across all endpoints including PEx, lung function, and QOL-B RSS vs pbo in Japanese pts, with a numerically higher effect."

Clinical • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Efficacy and safety of brensocatib in patients with non-cystic fibrosis bronchiectasis by exacerbation history: Analysis of the ASPEN trial (ERS 2025) - P3 | "Adverse events (AEs) were similar across tx arms; pts with ≥3 PEx had more AEs. Consistent with overall results, regardless of prior PEx number, brensocatib showed benefit across endpoints including PEx, lung function, and QOL-B RSS vs pbo."

Clinical • Bronchiectasis • Cystic Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Insmed to Present Multiple Abstracts at the European Respiratory Society Congress 2025 (PRNewswire) - "Notably, data from the Phase 2 trial in treprostinil palmitil inhalation powder (TPIP) in patients with pulmonary arterial hypertension (PAH) will be highlighted in the Congress's Abstracts Leading to Evolution in Respiratory Medicine Trials (ALERT) session, which showcases important, late-breaking clinical data from all respiratory disease areas. In addition, presentations include three prespecified subgroup analyses from the Phase 3 ASPEN trial evaluating the efficacy and safety of brensocatib, including Japanese patient data, as well as Health Outcomes and Economic Research from The Health Improvement Network® (THIN) database in France and the United Kingdom in patients with non-cystic fibrosis bronchiectasis (NCFB)."

Clinical data • Interstitial Lung Disease • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Arterial Hypertension

BRINSUPRI (brensocatib). (PubMed, Clin Ther) - No abstract available

Journal

ASPEN: Brensocatib's role in advancing bronchiectasis management in adults through neutrophil serine protease inhibition. (PubMed, Med) - "ASPEN demonstrated that 52 weeks of once-daily brensocatib (10 mg or 25 mg), compared to placebo, significantly reduced pulmonary exacerbations among adults with bronchiectasis.1 Additionally, time to the first exacerbation was significantly longer at the end of the 52-week treatment. Further, the decline in forced expiratory volume in 1 s was significantly lower in the 25-mg group, suggesting that brensocatib has a disease-modifying effect."

Journal • Bronchiectasis • Pulmonary Disease • Respiratory Diseases