FDA approves the first drug for non-cystic fibrosis bronchiectasis

On 12 August the US Food and Drug Administration approved Brinsupri (brensocatib) for the treatment of non-cystic fibrosis bronchiectasis in adults and in children aged 12 and older [s1][s2]. The agency classified it as a Type 1 new molecular entity and reviewed it under priority designation [s1]. It is the first drug approved in the United States for the condition.

Bronchiectasis is permanent widening and scarring of the airways, which fills with mucus and becomes chronically infected. Until now, management has meant airway clearance, antibiotics aimed at whatever is growing, and treating whatever underlying condition can be identified. Brensocatib does something different: it goes after the immune response rather than the bacteria.

The mechanism, and why it is unusual

Brensocatib is an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1) [s2][s3]. DPP-1 is the enzyme that activates neutrophil serine proteases — the destructive enzymes that neutrophils carry into inflamed tissue. In bronchiectasis, neutrophilic inflammation is associated with an increased risk of exacerbations and disease progression, and those proteases are key mediators of it [s3].

The therapeutic bet is that damping the enzymes neutrophils deploy, rather than the neutrophils themselves, reduces the self-perpetuating cycle of inflammation and airway damage without wholesale immunosuppression. Whether that bet holds up over years rather than a single trial year is not yet answerable.

The FDA approved two once-daily tablet strengths, 10 mg and 25 mg [s1].

What the phase 3 trial actually showed

The evidence base is the ASPEN trial, published in The New England Journal of Medicine in April [s3]. It randomised 1,721 patients — 1,680 adults and 41 adolescents — to brensocatib 10 mg once daily, 25 mg once daily, or placebo, and followed them for 52 weeks [s3].

The primary endpoint was the annualised rate of adjudicated pulmonary exacerbations. It was 1.02 in the 10 mg group, 1.04 in the 25 mg group and 1.29 with placebo, giving rate ratios versus placebo of 0.79 (95% CI, 0.68 to 0.92; adjusted P = 0.004) at 10 mg and 0.81 (95% CI, 0.69 to 0.94; adjusted P = 0.005) at 25 mg [s3].

That is roughly a one-fifth reduction in the rate of flare-ups — real, statistically robust, and modest in absolute terms. In practical arithmetic drawn from the trial's own numbers, the average patient on placebo had about 1.29 exacerbations over the year and the average patient on brensocatib had about one.

Secondary endpoints followed the same shape. The hazard ratio for time to first exacerbation was 0.81 (95% CI, 0.70 to 0.95) at 10 mg and 0.83 (95% CI, 0.70 to 0.97) at 25 mg [s3]. In each brensocatib group 48.5% of patients remained exacerbation-free at week 52, compared with 40.3% on placebo [s3].

Where the two doses diverge

Lung function is where the doses separate. At week 52, FEV1 had declined by 50 mL with the 10 mg dose, 24 mL with the 25 mg dose and 62 mL with placebo [s3]. Against placebo, that is a least-squares mean difference of 11 mL (95% CI, −14 to 37; adjusted P = 0.38) at 10 mg — not statistically significant — and 38 mL (95% CI, 11 to 65; adjusted P = 0.04) at 25 mg [s3].

So the higher dose slowed the decline in lung function and the lower dose did not demonstrably do so, while both cut exacerbations by a similar amount. The FDA approved both strengths [s1]. The trial does not resolve which is the better choice for any individual patient, and that is a question for a clinician with the full label in front of them, not something a reader can settle from a summary.

The incidence of adverse events was similar across groups, with one exception the trial flagged: a higher incidence of hyperkeratosis — thickening of the outer layer of the skin — with brensocatib [s3].

What this approval does and does not settle

It settles that a drug now exists with a regulatory indication for non-cystic fibrosis bronchiectasis, which changes the clinical conversation for a condition that has been managed entirely off-label and by inference from cystic fibrosis and COPD.

It does not settle durability. ASPEN ran 52 weeks [s3]. Bronchiectasis is a decades-long disease, and a 52-week exacerbation rate is a proxy for what patients care about — breathing, hospital admissions, staying alive. It does not settle who benefits most; the trial reported an overall population, and bronchiectasis is heterogeneous in cause, in the organisms colonising the airway, and in inflammatory profile. And a first-in-class approval always carries an open safety question that only post-marketing years answer.

What to watch: how the two doses are used in practice, whether the FEV1 signal at 25 mg holds up in longer follow-up, and whether the neutrophil-protease approach transfers to the other neutrophil-driven airway diseases where the same biology has been proposed.

Sources

• Drugs@FDA: BRINSUPRI (brensocatib), NDA 217673 — approval history — U.S. Food and Drug Administration, 2025-08-12
• NDA 217673 approval letter, Brinsupri (brensocatib) tablets — U.S. Food and Drug Administration, 2025-08-12
• Phase 3 Trial of the DPP-1 Inhibitor Brensocatib in Bronchiectasis — The New England Journal of Medicine, 2025-04-23