Abstract Rationale Verducatib (BI 1291583), a dipeptidyl peptidase 1 inhibitor, reduced the risk of adults with bronchiectasis experiencing a pulmonary exacerbation (PEx) in the Phase II AIRLEAF® study.1 Upon completion of treatment in AIRLEAF®, participants were eligible to enter the double-blind part of the CLAIRLEAF® rollover study (ongoing) to assess long-term safety and efficacy. Here, we present the final pooled data from all participants who received verducatib in the AIRLEAF® or CLAIRLEAF® (excluding those with cystic fibrosis bronchiectasis who rolled over from CLAIRAFLY®) studies. Methods In AIRLEAF®, 322 participants received one of three verducatib doses (1/2.5/5 mg) or placebo once daily for 24-48 weeks.1 Upon entering CLAIRLEAF®, those on active therapy in AIRLEAF® remained on the same blinded verducatib dose. Those in the placebo group in AIRLEAF® were blindly randomized (1:1:1) to a verducatib dose. As with the pre-specified analysis of the interim pooled data,2 in this final analysis, data from AIRLEAF® and CLAIRLEAF® were pooled to allow analyses with observational data up to Week 104. The analysis included 296 participants. For the efficacy analysis, the 2.5 and 5 mg verducatib doses were compared against the subtherapeutic 1 mg dose1 (due to the absence of a placebo group). The efficacy endpoints assessed were time to first PEx and PEx rate, both up to Week 104. Safety analyses were descriptive and based on treatment-emergent adverse events. Results The comparison of the 2.5 mg versus 1 mg dose of verducatib on time to first PEx revealed a 24% risk reduction (hazard ratio HR 0.76; 95% confidence interval CI 0.51-1.14). The effect of the 5 mg dose was a 13% reduction (HR 0.87; 95% CI 0.61-1.24). The 2.5 mg dose showed a 33% decrease (rate ratio RR 0.67; 95% CI 0.45-0.99) in PEx rate vs the 1 mg dose, whereas the 5 mg dose showed an 7% decrease (RR 0.93; 95% CI 0.67-1.31). The pooled safety data up to 104 weeks of exposure continue to support the known verducatib safety profile to date. Conclusions This pooled analysis demonstrates consistent positive effects of the 2.5 mg verducatib dose on PExs, and provides supportive evidence for the long-term efficacy and safety of verducatib in people with bronchiectasis. The 2.5 mg dose is being investigated in the Phase III AIRTIVITY™ study. 1Chalmers JD et al. Eur Respir J 2025; 65:2401551. 2Shteinberg M et al. Presented at ERS 2025. Poster: PA4960. This abstract is funded by: Boehringer Ingelheim
Shteinberg et al. (Fri,) studied this question.