New Subgroup Analyses from Phase 3 ASPEN Study of Brensocatib in Bronchiectasis Patients Consistent with Positive Overall Results

Insmed Incorporated, a biopharmaceutical company based in Bridgewater, New Jersey, recently shared promising late-breaking subgroup data from its Phase 3 ASPEN study. This global, randomized, double-blind, placebo-controlled trial investigates the efficacy, safety, and tolerability of brensocatib in patients with non-cystic fibrosis bronchiectasis. The findings were presented at the CHEST 2024 Annual Meeting in Boston, showcasing the potential of brensocatib to become a groundbreaking treatment for this condition.

James Chalmers, lead investigator of the study and a Professor and Consultant Respiratory Physician at the University of Dundee, highlighted the enthusiasm among both physicians and patients regarding the trial's positive results. Chalmers noted that the disease's heterogeneous nature makes the consistent positive impact of brensocatib across most predefined subgroups particularly noteworthy. The study revealed that brensocatib, especially at a 25 mg dose, was effective in slowing lung function decline, as measured by FEV1, across all subgroups. This outcome underscores the potential of brensocatib to benefit a diverse range of patients.

The ASPEN study demonstrated that the annualized rate of pulmonary exacerbations was lower for patients treated with brensocatib at both 10 mg and 25 mg doses compared to those receiving a placebo. A separate analysis showed that brensocatib 25 mg resulted in a reduced decline in post-bronchodilator FEV1 at Week 52 across all predefined subgroups, aligning with the overall trial population results.

Brensocatib was generally well-tolerated during the study. The most common treatment-emergent adverse events (TEAEs) occurring in at least 5% of patients treated with either dose of brensocatib and more frequently than in the placebo group included COVID-19, nasopharyngitis, cough, and headache. These TEAEs occurred at rates of 15.8%, 20.9%, and 15.8% for COVID-19; 7.7%, 6.3%, and 7.6% for nasopharyngitis; 7.0%, 6.1%, and 6.4% for cough; and 6.7%, 8.5%, and 6.9% for headache in the brensocatib 10 mg, brensocatib 25 mg, and placebo groups, respectively.

Martina Flammer, Chief Medical Officer of Insmed, expressed excitement about the subgroup findings, which build on previously shared positive results. Flammer emphasized that the consistency of efficacy observed, particularly at the higher dose, supports the potential of brensocatib to significantly alter the treatment landscape for bronchiectasis. Insmed plans to submit a New Drug Application (NDA) for brensocatib to the U.S. Food and Drug Administration (FDA) in late 2024, with anticipated U.S. market launch by mid-2025, followed by launches in Europe and Japan in the first half of 2026.

The ASPEN study, involving more than 460 trial sites across nearly 40 countries, focused on assessing brensocatib's potential in treating bronchiectasis. Participants included 1,680 adults and 41 adolescents. Adult patients were randomized 1:1:1 to receive brensocatib 10 mg, brensocatib 25 mg, or placebo once daily for 52 weeks, followed by 4 weeks off treatment. The results demonstrated that brensocatib has the potential to become the first approved treatment for patients with bronchiectasis, as well as the first approved dipeptidyl peptidase 1 (DPP1) inhibitor.

Brensocatib is a small molecule, oral, reversible DPP1 inhibitor that is under development for bronchiectasis, CRSsNP, and other neutrophil-mediated diseases. DPP1 is responsible for activating neutrophil serine proteases (NSPs), which play a key role in pathogen destruction and inflammatory mediation. By inhibiting DPP1, brensocatib may reduce the harmful effects of excessive NSP activity in chronic inflammatory lung diseases.

Insmed is dedicated to advancing therapies to improve patients' lives, with a focus on pulmonary and inflammatory conditions. The company has offices and research facilities in the United States, Europe, and Japan, and has been recognized as a top employer in the biopharmaceutical industry for three consecutive years.