- 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.
- 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.
- 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.
- Long-term increased risk for infection not known.