Bronchiectasis: brensocatib shows promise in phase 2 trial

  • Chalmers JD & al.
  • N Engl J Med
  • 7 Sep 2020

  • curated by Miriam Davis, PhD
  • Clinical Essentials
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Takeaway

  • The dipeptidyl peptidase-1 (DPP-1) inhibitor brensocatib prolonged the time to first exacerbation and reduced frequency of exacerbations in a phase 2 trial of patients with noncystic fibrosis bronchiectasis.
  • DPP-1 is an enzyme activating neutrophil serine proteases thought to be involved in neutrophilic inflammation underlying exacerbations.

Why this matters

  • Exacerbations of bronchiectasis yield poorer QoL and increased mortality.
  • Findings of this phase 2 trial warrant progression to phase 3.

Study design

  • Phase 2, randomized, double-blind, placebo-controlled trial of 256 patients (with ≥2 exacerbations in the past year) who were assigned to receive placebo, 10 mg brensocatib, and 25 mg brensocatib once daily for 24 weeks.
  • Primary outcome: time to first exacerbation.
  • Funding: Insmed.

Key results

  • Both brensocatib groups had longer time to first exacerbation:
    • Placebo group: 67 days.
    • 10 mg brensocatib: 134 days.
    • 25 mg brensocatib: 96 days.
  • Adjusted HRs for exacerbation vs placebo:
    • 10 mg brensocatib: 0.58 (P=.03).
    • 25 mg brensocatib: 0.62 (P=.046).
  • Exacerbation frequency was lower with 10 mg brensocatib:
    • 10 mg group vs placebo: incidence rate ratio: 0.64 (P=.04).
    • 25 mg group vs placebo: incidence rate ratio: 0.75 (P=.17).
  • Both brensocatib groups had a higher frequency of adverse events.

Limitations

  • Long-term increased risk for infection not known.