A NEW study has demonstrated that both 20 mg and 40 mg doses of the DPP-1 inhibitor HSK31858 significantly reduces the frequency of exacerbations in adults with bronchiectasis, without increasing adverse events, suggesting a promising new treatment avenue for this chronic respiratory condition.
Bronchiectasis is a chronic lung disease characterised by persistent airway inflammation, recurrent infections, and frequent exacerbations, often driven by excessive neutrophil activity. Current treatments are limited, and there is a pressing need for therapies that can effectively reduce exacerbation rates and improve patient outcomes. HSK31858 is a novel, reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), an enzyme involved in neutrophil activation. This phase 2, multicentre, double-blind, randomised, placebo-controlled trial (SAVE-BE) was conducted across 25 tertiary centres in China to evaluate the efficacy and safety of HSK31858 in adults with bronchiectasis who had experienced at least two exacerbations in the preceding year.
A total of 226 participants were randomly assigned to receive either 20 mg HSK31858, 40 mg HSK31858, or placebo once daily for 24 weeks. The full analysis set included 74 patients in the 20 mg group, 75 in the 40 mg group, and 75 in the placebo group, with 61% female and 39% male participants. The mean annualised exacerbation frequency was 1.00 per person-year (SD 1.44) in the 20 mg group, 0.75 per person-year (SD 1.37) in the 40 mg group, and 1.88 per person-year (SD 1.97) in the placebo group. The least-squares mean frequency of exacerbations was 1.05 per person-year (95% CI 0.73–1.51) for 20 mg, 0.83 per person-year (0.55–1.25) for 40 mg, and 2.01 per person-year (1.53–2.63) for placebo. The incidence rate ratio compared to placebo was 0.52 (95% CI 0.34–0.80; p=0.0031) for 20 mg and 0.41 (0.26–0.66; p=0.0002) for 40 mg. Adverse events occurred at similar rates across all groups, with no increase in serious or special interest events such as hyperkeratosis or life-threatening infections.
These findings indicate that HSK31858, at both tested doses, is effective in reducing exacerbation frequency in adults with bronchiectasis, with a favourable safety profile. For clinical practice, this suggests that targeting neutrophilic inflammation via DPP-1 inhibition could become an important strategy in managing bronchiectasis, potentially improving quality of life and reducing healthcare burden. Further research in larger and more diverse populations, as well as longer-term studies, will be essential to confirm these results and explore the long-term benefits and safety of HSK31858. Clinicians should remain alert to emerging therapies in this area, as they may soon offer new hope for patients with limited treatment options.
Reference
Zhong NS et al. Effects of the DPP-1 inhibitor HSK31858 in adults with bronchiectasis in China (SAVE-BE): a phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Respir Med. 2025;13(5):414-24
