brensocatib (INS1007) / Insmed, AstraZeneca - LARVOL DELTA

Efficacy and safety of brensocatib in Japanese patients with non-cystic fibrosis bronchiectasis: Analysis of the ASPEN trial (ERS 2025) - No abstract available

Clinical • Bronchiectasis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis 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) - No abstract available

Clinical • Bronchiectasis • Genetic Disorders • Immunology • Infectious Disease • 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) - No abstract available

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

Salivary Dipeptidyl Peptidase-1 and Derived Proinflammatory Markers in Primary Ciliary Dyskinesia Patients: Implications for Brensocatib Therapy (ATS 2025) - "Salivary DPP-1 gene expression is elevated in patients with PCD, with significant differences observed between those with bronchiectasis and healthy controls, as well as variations between the MTD and ODA subtypes. The increased levels of DPP-1 in PCD patients could indicate a potential response to Brensocatib. Further research to evaluate the response in PCD with bronchiectasis is needed."

Clinical • IO biomarker • Bronchiectasis • Otorhinolaryngology • Pulmonary Disease • Respiratory Diseases • CXCL8 • ELANE • IL6 • TLR4

Exacerbation Rate and Lung Function in Adolescent Patients With Non-cystic Fibrosis Bronchiectasis: An Analysis of the ASPEN Trial (ATS 2025) - P3 | "Adverse events were similar across treatment groups and consistent with overall ASPEN results. Conclusions In adolescent patients from the ASPEN trial, both 10-mg and 25-mg brensocatib were associated with numerical improvements in the annualized rate of pulmonary exacerbations and improved lung function outcomes vs placebo."

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

Changes in Lung Function in Patients With Non-cystic Fibrosis Bronchiectasis Who Did or Did Not Have On-study Pulmonary Exacerbations: An Analysis of the ASPEN Trial (ATS 2025) - P3 | "Conclusions Overall, greater lung function decline was observed in patients who had on-study pulmonary exacerbations vs those who did not. Brensocatib 25-mg reduced lung function decline vs placebo regardless of whether patients had on-study exacerbations, consistent with overall ASPEN results."

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

Efficacy of Brensocatib in Patients With Eosinophilic Bronchiectasis: An Analysis of the ASPEN Trial (ATS 2025) - P3 | "Adverse events were similar across treatment groups, and consistent with the overall ASPEN results. Conclusions Consistent with the overall study population, both brensocatib doses reduced the annualized rate of exacerbations, and brensocatib 25-mg reduced lung function decline and numerically improved patient-reported symptoms regardless of high or low eosinophil counts at baseline."

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

Efficacy of Brensocatib in Patients With Non-Cystic Fibrosis Bronchiectasis With vs Without Maintenance Use of Macrolides: An Analysis of the ASPEN Trial (ATS 2025) - P3 | "Adverse events were similar across treatment groups, and consistent with the overall ASPEN results. Conclusions Consistent with the overall study population, both brensocatib doses reduced the annualized rate of exacerbations, and brensocatib 25-mg reduced lung function decline and numerically improved patient-reported symptoms regardless of maintenance macrolide use at baseline."

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

Lower Airway Dysbiosis in Nontuberculous Mycobacterial Lung Disease Drives a Neutrophil Extracellular Trap-endotype and Lung Injury (ATS 2025) - "The WILLOW trial reported a reduction in exacerbations with Brensocatib (cathepsin-C inhibitor that can disintegrate NET), thus identifying NET as a treatable trait, but the study did not include NTM+ patients... In this study, we identified that lower airway metacommunities had different NET levels, and in NTM+ subjects, Mycobacterium had a synchronous occurrence with oral commensals as well as with NETs. Using a bedside-back-to-the-bench paradigm, we confirmed in our murine model that NTM drives NET formation and lung inflammation/injury in dysbiosis. Our study suggests a pathogenic role for NET in NTM-LD and future studies could help identify a NET-predominant endotype as a treatable trait in NTM-LD."

Dysbiosis • Nontuberculous mycobacteria • Bronchiectasis • Inflammation • Nontuberculous Mycobacterial Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • CTSC • PD-1

What is brensocatib? (PubMed, Arch Dis Child) - No abstract available

Journal

BiRCh: A Study of the Efficacy and Safety of Brensocatib in Participants With Chronic Rhinosinusitis Without Nasal Polyps (CRSsNP) (clinicaltrials.gov) - P2 | N=288 | Active, not recruiting | Sponsor: Insmed Incorporated | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Nasal Polyps • Otorhinolaryngology • Respiratory Diseases • Sinusitis

A profile of brensocatib for non-cystic fibrosis bronchiectasis. (PubMed, Expert Rev Respir Med) - "Finally, we summarize the current marketplace for brensocatib, including the unmet for effective therapies for bronchiectasis, and the status of other potential treatments undergoing clinical trials. Brensocatib is the first-in-class DPP1 inhibitor that shows promise as a treatment for patients with bronchiectasis."

Journal • Review • Bronchiectasis • Genetic Disorders • Immunology • Inflammation • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Recent Progress and Anticipated Milestones by Program (PRNewswire) - "Regulatory submissions for brensocatib in the EU and UK have been accepted, with submission in Japan planned for 2025. Insmed anticipates commercial launches for each territory in 2026, pending approval."

Filing • Launch • Bronchiectasis

Recent Progress and Anticipated Milestones by Program (PRNewswire) - "Insmed completed enrollment in the Phase 2b BiRCh study of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) with 288 patients. The Company remains on track to report topline results by the end of 2025; The Company continues to enroll patients in the Phase 2b CEDAR study of brensocatib in patients with hidradenitis suppurativa (HS). Based on current enrollment rates, the Company anticipates the interim futility analysis from the first 100 patients to complete Week 16 of the trial in the first half of 2026."

Enrollment closed • P2b data • Trial status • Hidradenitis Suppurativa • Respiratory Diseases

Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis. (PubMed, N Engl J Med) - P3 | "Among patients with bronchiectasis, once-daily treatment with brensocatib (10 mg or 25 mg) led to a lower annualized rate of pulmonary exacerbations than placebo, and the decline in FEV1 was less with the 25-mg dose of brensocatib than with placebo. (Funded by Insmed; ASPEN ClinicalTrials.gov number, NCT04594369; EudraCT number, 2020-003688-25.)."

Clinical • Journal • P3 data • Bronchiectasis • Inflammation • Pulmonary Disease • Respiratory Diseases

Brensocatib in Bronchiectasis - A New Sheriff in Town? (PubMed, N Engl J Med) - No abstract available

Journal • Bronchiectasis • Pulmonary Disease • Respiratory Diseases

New England Journal of Medicine Publishes Positive Results from Insmed's Pivotal Phase 3 ASPEN Study of Brensocatib in Patients with Bronchiectasis (PRNewswire) - P3 | N=1,767 | ASPEN (NCT04594369) | Sponsor: Insmed Incorporated | "As previously reported, the ASPEN study met its primary endpoint, with both brensocatib doses achieving statistical and clinical significance for the reduction in the annualized rate of pulmonary exacerbations versus placebo over the 52-week treatment period. The annualized rate of exacerbations was 1.02 for brensocatib 10 mg, 1.04 for brensocatib 25 mg, and 1.29 for placebo. These rates were significantly lower in the brensocatib 10 mg and 25 mg groups versus placebo with rate ratios of 0.79 (adjusted P=0.004) and 0.81 (adjusted P=0.005), respectively...Brensocatib was well-tolerated in the study."

P2 data • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis

Insmed to Present 11 Abstracts from Across Its Respiratory Portfolio at the American Thoracic Society 2025 International Conference (PRNewswire) - "Presentations include several prespecified subgroup analyses from the Phase 3 ASPEN study evaluating the efficacy and safety of brensocatib, new health economics and outcomes research in MAC lung disease, and clinical data from the Phase 2a study of treprostinil palmitil inhalation powder (TPIP) in pulmonary hypertension associated with interstitial lung disease (PH-ILD).1"

Clinical data • Bronchiectasis • Interstitial Lung Disease • Non‐Cystic Fibrosis Bronchiectasis

Insmed Reports Fourth-Quarter and Full-Year 2024 Financial Results and Provides Business Update (PRNewswire) - "ARIKAYCE global revenue grew 19% in 2024 compared to 2023...The Company continues to anticipate a topline readout for ENCORE in the first quarter of 2026, with the submission of a supplementary new drug application (sNDA) to the FDA for ARIKAYCE in all patients with MAC lung disease in the U.S. expected later in 2026...Regulatory submissions for brensocatib in the EU, UK, and Japan are planned for 2025, with commercial launches anticipated in 2026...The Phase 2b BiRCh study of brensocatib in patients with chronic rhinosinusitis without nasal polyps (CRSsNP) remains on track to report topline results by the end of 2025...The Company plans to initiate a Phase 3 study of TPIP in patients with PH-ILD in the second half of 2025. Enrollment in the Phase 2b study of TPIP in pulmonary arterial hypertension (PAH) completed in December 2024...Insmed continues to anticipate topline data from the study in the middle of 2025."

Commercial • Filing • New P3 trial • P2b data • P3 data: top line • Infectious Disease • Nasal Polyps • Pulmonary Arterial Hypertension • Pulmonary Disease

Insmed Announces that FDA Does Not Currently Plan to Hold Advisory Committee Meeting to Discuss New Drug Application for Brensocatib in Patients with Bronchiectasis (PRNewswire) - "Insmed Incorporated...today announced that the U.S. Food and Drug Administration (FDA) has informed the Company that it does not currently plan to hold an advisory committee meeting to discuss the New Drug Application (NDA) for brensocatib for patients with non-cystic fibrosis bronchiectasis. The FDA provided this update in its Day 74 communication to Insmed."

FDA event • Bronchiectasis

FDA Grants Priority Review to Insmed’s Brensocatib for Treatment of Bronchiectasis with PDUFA Target Action Date Set for August 12, 2025 (PRNewswire) - "Insmed Incorporated...announced that the U.S. Food and Drug Administration (FDA) has accepted the Company's New Drug Application (NDA) for brensocatib for patients with non-cystic fibrosis bronchiectasis. In its Day 60 communication to Insmed, the FDA granted Priority Review to the NDA and set a target action date of August 12, 2025, under the Prescription Drug User Fee Act (PDUFA). At present, the FDA has not indicated whether an advisory committee will be convened to discuss the application....This NDA is based on data from the landmark Phase 3 ASPEN study, which 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 versus placebo over the 52-week treatment period....Insmed plans to file regulatory submissions for brensocatib in the EU, UK, and Japan in 2025, with commercial launches anticipated in 2026, pending approval in each territory."

Filing • Launch • PDUFA • Priority review • Non‐Cystic Fibrosis Bronchiectasis

Broad Immunomodulatory Effects of the Dipeptidyl-peptidase-1 Inhibitor Brensocatib in Bronchiectasis: Data from the Phase 2, Double-Blind, Place-controlled WILLOW Trial. (PubMed, Am J Respir Crit Care Med) - P2 | "Brensocatib exerts broad anti-inflammatory effects beyond its known effects on serine proteases. Clinical trial registration available at www."

Journal • P2 data • Bronchiectasis • Inflammation • Pulmonary Disease • Respiratory Diseases • CCL11 • CCL3 • CCL8 • CXCL10 • ELANE • IL6 • IL7 • MPO • MUC5AC

Brensocatib in patients with bronchiectasis: subgroup analyses from the WILLOW trial. (PubMed, ERJ Open Res) - "Safety results were similar across subgroups. Patients treated with brensocatib had a numerically longer time to first exacerbation and reduced annualised rate of exacerbation versus placebo across all key baseline disease characteristics."

Journal • Bronchiectasis • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases

Evaluation of Neutrophil Elastase Inhibitors as Potential Therapies for ELANE Associated Neutropenia. (PubMed, J Cell Immunol) - "In contrast, other NE inhibitors, i.e., sivelestat, BAY-678, and GW311616 and the DPP1 inhibitor, brensocatib, showed no effect on neutrophil differentiation. Molecular docking studies showed that MK0339 binds to an alternative site on the NE protein compared to other inhibitors with greater inhibitor-NE protein stability, suggesting a unique mechanism of action and supporting further investigation of MK0339 as a therapy for ELANE associated neutropenia."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Musculoskeletal Pain • Myelodysplastic Syndrome • Neutropenia • Oncology • Pain • Transplantation • CD14 • CD34 • CEACAM8 • ELANE • ITGAM

CEDAR: A Study of the Efficacy and Safety of Brensocatib in Adults With Moderate to Severe Hidradenitis Suppurativa (HS) (clinicaltrials.gov) - P2 | N=204 | Recruiting | Sponsor: Insmed Incorporated | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatology • Hidradenitis Suppurativa • Immunology