New data from subgroup analyses of the Phase 3 ASPEN study reveal that brensocatib, an investigational drug by Insmed, demonstrates consistent efficacy in reducing pulmonary exacerbations and slowing lung function decline in patients with bronchiectasis across various subgroups. These findings, presented at the CHEST 2024 Annual Meeting, reinforce the potential of brensocatib as a treatment for this heterogeneous disease.
The ASPEN trial, a global, randomized, double-blind, placebo-controlled study, assessed the efficacy, safety, and tolerability of brensocatib in patients with non-cystic fibrosis bronchiectasis. The subgroup analyses provide a more granular view of the drug's performance across different patient populations.
Consistent Reduction in Exacerbations
The analyses showed that brensocatib, at both 10 mg and 25 mg doses, favored a reduction in the annualized rate of pulmonary exacerbations compared to placebo across almost all subgroups. This consistency is particularly significant given the variability of bronchiectasis, according to lead study investigator James Chalmers, MBChB, Ph.D., Professor and Consultant Respiratory Physician at the School of Medicine, University of Dundee, UK.
Slowing Lung Function Decline
Further analysis revealed that brensocatib 25 mg demonstrated a reduced decline in post-bronchodilator FEV1 (Forced Expiratory Volume in one second) at Week 52 compared to placebo for all pre-specified subgroups. This suggests that brensocatib may have a disease-modifying effect by preserving lung function over time.
Safety and Tolerability
Brensocatib was generally well-tolerated in the study. The most common treatment-emergent adverse events (TEAEs) occurring in at least 5.0% of patients treated with either dose of brensocatib and more frequently than in placebo were COVID-19 (15.8%, 20.9%, 15.8%), nasopharyngitis (7.7%, 6.3%, 7.6%), cough (7.0%, 6.1%, 6.4%), and headache (6.7%, 8.5%, and 6.9%) for brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively.
Regulatory Plans and Future Outlook
Insmed plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for brensocatib in bronchiectasis patients in the fourth quarter of 2024. Pending regulatory approvals, the company anticipates a U.S. launch in mid-2025, followed by launches in Europe and Japan in the first half of 2026. If approved, brensocatib would be the first approved treatment for patients with bronchiectasis and the first approved dipeptidyl peptidase 1 (DPP1) inhibitor.
About Brensocatib and DPP1 Inhibition
Brensocatib is an oral, reversible inhibitor of DPP1. DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils. By inhibiting DPP1, brensocatib may reduce the damaging effects of inflammatory diseases like bronchiectasis, where excessive active NSPs cause lung destruction and inflammation.
