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Respiratory · Clinical trials

Bronchiectasis Clinical Trials

Approved therapies, the pivotal-trial endpoints they were judged on, the magnitude of benefit — and the drugs that failed their endpoints, and why.

Indication overview

About bronchiectasis — and why its trials are hard

Bronchiectasis is a chronic disease defined by permanent, abnormal dilation of the bronchi, driven by a self-perpetuating cycle of impaired mucus clearance, chronic bacterial infection, neutrophil-dominant airway inflammation and progressive structural damage. Patients suffer chronic productive cough, recurrent exacerbations, breathlessness and declining lung function; Pseudomonas aeruginosa colonization marks worse prognosis. Non-cystic-fibrosis bronchiectasis has diverse causes including prior infection, immunodeficiency, primary ciliary dyskinesia and allergic bronchopulmonary aspergillosis. For decades management was entirely supportive and borrowed from other diseases: airway clearance techniques, treatment of exacerbations, long-term macrolides in selected patients, and inhaled antibiotics for chronic Pseudomonas, none FDA-approved specifically for bronchiectasis. Multiple inhaled-antibiotic programs failed to earn a bronchiectasis indication. That changed in August 2025 when brensocatib, an oral reversible inhibitor of dipeptidyl peptidase-1 (DPP-1) that blocks activation of neutrophil serine proteases, became the first drug approved for the condition after the positive Phase 3 ASPEN trial. The annualized pulmonary exacerbation rate is the central efficacy endpoint in this field.

Indication
Bronchiectasis
ICD-10-CM
J47.9 — Bronchiectasis, uncomplicated

Approved therapies & pivotal evidence

What's been approved — and by how much it moved the endpoint

Drug (brand)ApprovedSettingPivotal trialPrimary endpointMagnitude of benefit
brensocatib (Brinsupri)2025First and only FDA-approved treatment for non-cystic-fibrosis bronchiectasis, ages 12 and olderASPEN (Phase 3)Annualized rate of pulmonary exacerbations over 52 weeksSignificant reduction in annualized exacerbation rate vs placebo (~21% for the 10 mg and ~19% for the 25 mg dose); reduced lung-function decline

Where trials have failed

Drugs that missed their endpoint — and what contributed

The most instructive lessons in bronchiectasis development come from programmes that failed the endpoint that mattered.

Drug / trialEndpoint outcomeWhat contributed
inhaled ciprofloxacin dry powder — RESPIRE 1 and RESPIRE 2 (Phase 3)Inconsistent results across regimens/trials; co-primary exacerbation endpoints not reliably met, and no bronchiectasis approval followedHeterogeneous patient populations, variable definitions of exacerbation, and dosing-schedule differences produced inconsistent, underpowered signals
inhaled liposomal ciprofloxacin — ORBIT-3 and ORBIT-4 (Phase 3)Only one of the two identical trials met the primary endpoint (time to first exacerbation); overall program failed to secure approvalLack of replication across the paired trials and inconsistent exacerbation effects undermined the regulatory case

Choosing the right endpoint

Primary endpoints that matter in bronchiectasis trials

  • Annualized pulmonary exacerbation rate — The pivotal efficacy endpoint, used in ASPEN and inhaled-antibiotic trials
  • Time to first exacerbation — Co-primary/secondary endpoint in several inhaled-antibiotic programs
  • FEV1 / rate of lung-function decline — Physiologic endpoint capturing structural disease progression
  • Bacterial load / Pseudomonas density — Microbiologic endpoint relevant to inhaled-antibiotic mechanisms
  • Quality of Life-Bronchiectasis (QOL-B) — Validated patient-reported symptom and quality-of-life measure

How iNGENū runs bronchiectasis trials

Physician-led design, built for FDA submission

Endpoint & biomarker strategy

Board-certified specialists design endpoints and patient selection aligned to current FDA guidance for this indication.

FDA-ready data

Built to ICH-GCP and 21 CFR 312.120, with direct FDA submission — data accepted by the FDA, EMA and MHRA.

Faster, lower-cost delivery

~4-week ethics via the TGA CTN scheme, up to 43.5% R&D rebate, and 80–90% below US CRO cost.

Planning a bronchiectasis trial?
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Frequently asked questions

Bronchiectasis clinical trials — FAQs

Was there any approved bronchiectasis drug before 2025?
No. Until brensocatib's August 2025 approval, no therapy was FDA-approved specifically for bronchiectasis; care relied on airway clearance, macrolides and off-label inhaled antibiotics.
How does brensocatib work?
It reversibly inhibits DPP-1, the enzyme that activates neutrophil serine proteases such as neutrophil elastase, thereby dampening the neutrophilic inflammation that drives airway damage and exacerbations.
Why did inhaled antibiotics fail to get approved for bronchiectasis?
Large Phase 3 programs like RESPIRE and ORBIT produced inconsistent, non-replicated exacerbation results, so regulators did not grant a bronchiectasis-specific indication.

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