Insmed’s brensocatib demonstrates a reduction in exacerbations and lung function decline measures compared to placebo in a 52-week phase 3 trial for non-cystic fibrosis bronchiectasis.

RT’s Three Key Takeaways:

• Efficacy and Safety: The ASPEN phase 3 study confirmed that brensocatib is an effective and safe treatment for non-cystic fibrosis bronchiectasis, demonstrating significant reductions in pulmonary exacerbations compared to placebo.
• Slowed Lung Function Decline: The study showed that brensocatib not only reduced the annualized rate of pulmonary exacerbations but also slowed the decline in lung function, with patients experiencing less reduction in FEV1 and FVC compared to those on placebo.
• Path to FDA Approval: Following these positive results, Insmed plans to file a New Drug Application with the FDA in the fourth quarter of 2024, with the potential for brensocatib to become the first approved treatment for bronchiectasis.

Insmed Inc announced additional positive results from the ASPEN phase 3 study of brensocatib in patients with non-cystic fibrosis bronchiectasis, confirming its efficacy, safety, and potential to reduce pulmonary exacerbations. 

The results were presented at the 7th World Bronchiectasis Conference on July 4 in Dundee, Scotland.

As previously announced, the ASPEN study 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. 

The annualized rate of exacerbations was 1.015 for the brensocatib 10 mg group, 1.036 for the brensocatib 25 mg group, and 1.286 for placebo, representing a 21.1% risk reduction from placebo for the brensocatib 10 mg group (p=0.0019) and a 19.4% risk reduction for the 25 mg group (p=0.0046). 

Both dosage strengths of brensocatib also met several secondary endpoints, including significantly prolonging the time to first exacerbation and significantly increasing the odds of remaining exacerbation-free over the treatment period.

“The ASPEN findings are critically important given that there is no approved treatment for bronchiectasis and there remains an urgent need for a therapy that can both reduce pulmonary exacerbations and lessen the burden of this disease. The data announced today further underscore the positive impact brensocatib may have on patients if approved,” says lead study investigator James Chalmers, MBChB, PhD, professor and consultant respiratory physician at the School of Medicine, University of Dundee, in a release. 

He continues, “Bronchiectasis is a progressive disease that causes patients to lose lung function over time. Therefore, I am particularly encouraged by the data which showed that the 25 mg dose of brensocatib may slow the rate of decline of FEV1 (forced expiratory volume over one second) and FVC (forced vital capacity), which represent clinically meaningful parameters of lung function that physicians consider important outcome measures.”

Assessing Changes in Lung Function

The study assessed change in lung function, as measured by change from baseline in post-bronchodilator FEV1 at week 52, a key secondary endpoint. Patients treated with brensocatib 25 mg demonstrated significantly less FEV1 decline, preserving more lung function as compared to placebo. Patients in the placebo arm lost on average 62 mL of FEV1 in one year. 

In addition, new data was presented at the World Bronchiectasis Conference measuring the change from baseline in post-bronchodilator FVC at week 52, another measure of lung function and an exploratory endpoint in the study. Patients treated with brensocatib 25 mg showed nominally significantly less decline in FVC compared to placebo.

Patients in both dosage groups of brensocatib experienced numerical improvements in change from baseline in the Quality of Life-Bronchiectasis Respiratory Symptom Domain Score, with the brensocatib 25 mg dose group demonstrating a nominally significant improvement of 3.8 points versus placebo (p=0.0004). Improvements in patient-reported Quality of Life-Bronchiectasis Respiratory Symptom Domain Score were seen as early as four weeks in both brensocatib arms. 

New data was presented at the World Bronchiectasis Conference on the change in average daily bronchiectasis exacerbation and symptom tool (BEST) score, an exploratory endpoint, which is a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations. Patients treated with brensocatib 25 mg showed a nominally significant 1-point decrease in BEST score compared to placebo.

Brensocatib was well-tolerated in the study and demonstrated a favorable safety profile. Treatment-emergent adverse events occurring in at least 5% 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%, 6.1%, 6.4%), and headache (6.7%, 8.5%, and 6.9%) for brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively.

Seeking Regulatory Approval

Insmed plans to file a New Drug Application with the US Food and Drug Administration for brensocatib in patients with bronchiectasis in the fourth quarter of 2024. Pending regulatory approvals, Insmed anticipates a US launch for brensocatib 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 as well as the first approved dipeptidyl peptidase 1 inhibitor—a new mechanism of action with the potential to address a range of neutrophil-mediated diseases.

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