Brensocatib fails in severe COVID-19 

Brensocatib did not improve the health status of patients with severe COVID-19, even though there was an association between neutrophilic inflammation and mortality in COVID-19, and active neutrophil elastase was decreased.

A randomised-controlled trial investigated whether the oral dipeptidyl peptidase-1 (DPP1) inhibitor brensocatib delivered clinical benefits for patients with hospitalised COVID-19 [1]. The included patients (n=404) received brensocatib or placebo for 28 days. The primary endpoint was the improvement participants made on a 7-point WHO ordinal scale representing clinical status after 4 weeks of therapy. Ms Holly Keir (University of Dundee, UK) presented the results.

On day 29, 18.7% of the participants in the placebo arm and 14.7% of the participants in the brensocatib arm had reached the most favourable score on the ordinal scale: ‘not hospitalised, no limitations on activities’. In addition, 10.7% and 15.3% of the participants had died in the placebo arm and the intervention arm, respectively. Thus, there appeared to be a small benefit for the placebo arm over the brensocatib arm (adjusted OR 0.72; P=0.008).

The adverse event rates were similar for the brensocatib arm (44.8%) and the placebo arm (46.3%), with no significant differences in skin disorders or infections between the 2 groups. Ms Keir added that the research team demonstrated that active neutrophil elastase levels were in fact reduced in participants receiving brensocatib (P<0.0001), but that this did not lead to a positive treatment effect.

1. Keir HR, et al. Dipeptidyl Peptidase-1 Inhibition in Patients Hospitalized with COVID-19: a Multicentre Randomized Double-Blind Placebo Controlled Trial. ALERT 3, RCT2883, ERS International Congress 2022, Barcelona, Spain, 4–6 September.

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Posted on 30 October 2022