Dipeptidylpeptidase-1 inhibitor lowers exacerbation incidence in bronchiectasis

Key takeaways:

• HSK31858 given as 20 mg or 40 mg performed better than placebo in outcomes related to pulmonary exacerbations.
• All three groups had a similar proportion of patients reporting a treatment-emergent adverse event.

Among Chinese adults with bronchiectasis and exacerbations in the past year, 24-week dipeptidylpeptidase-1 inhibitor HSK31858 lowered exacerbation incidence, according to a poster at the European Respiratory Society International Congress.

“HSK31858 is a novel, oral, small molecule that could totally inhibit [neutrophil serine protease] activity, both in vitro and in vivo,” Wei-Jie Guan, PhD, of the First Affiliated Hospital of Guangzhou Medical University and Guangzhou Institute for Respiratory Health, said in a prerecorded poster presentation.

In this randomized, double-blind, placebo-controlled phase 2 trial, Guan and colleagues assessed 226 Chinese adults with bronchiectasis who experienced at least two exacerbations in the past year to find out how a 20 mg and 40 mg once-daily dose of HSK31858 vs. placebo impact exacerbation incidence at 24 weeks.

As Healio previously reported, the ASPEN trial found that Insmed’s oral, reversible inhibitor of dipeptidylpeptidase-1 brensocatib lowered the annualized pulmonary exacerbation rate and was well tolerated among patients with non-cystic fibrosis bronchiectasis.

Within the total cohort, 75 patients received 20 mg HSK31858, 76 patients received 40 mg HSK31858 and the last 75 patients received placebo.

The incidence rate of exacerbations in the placebo group was 1.88 events per patient-year, and researchers found that this rate was significantly lower in the 20 mg HSK31858 group (1 event per patient-year; HR = 0.52, 95% CI, 0.34-0.79; P = .0026), as well as in the 40 mg HSK31858 group (0.75 events per patient-year; HR = 0.4, 95% CI, 0.25-0.64; P = .0001).

Additionally, the time to first exacerbation was significantly prolonged among those who received 20 mg HSK31858 and those who received 40 mg HSK31858 vs. placebo (mean, 147.2 days and 146.2 days vs. 124.1 days), according to the poster.

Researchers also found that patients taking 20 mg HSK31858 and patients taking 40 mg HSK31858 had significant decreases in sputum neutrophil serine proteases mean concentrations vs. patients taking placebo over the study period.

“[In bronchiectasis] upon pathogen stimulation, the activated neutrophils may release an excessive amount of neutrophil serine proteases, or NSP, which includes neutrophil elastase, proteinase 3 and cathepsin G, which have been associated with the progression of bronchiectasis,” Guan said in his prerecorded presentation.

In terms of safety, all three groups had a similar proportion of patients who experienced a treatment-emergent adverse event (20 mg HSK31858, 86.5%; 40 mg HSK31858, 88%; placebo, 85.3%), according to the poster.

The most frequently occurring treatment-emergent adverse events in the 20 mg HSK31858 group, the 40 mg HSK31858 group and the placebo group included upper respiratory tract infections (27%; 17.3%; 10.7%), increased cough (9.5%; 21.3%; 12%), hemoptysis (9.5%; 10.7%; 13.3%) and increased body weight (10.8%; 17.3%; 6.7%).

“We have planned to do [a] phase 3 trial with HSK31858, which will be pending at the end of this year,” Guan said in the prerecorded presentation.