Brensocatib (INS1007 or AZD7986) is an experimental treatment that Insmed is developing for non-cystic fibrosis bronchiectasis (NCFB) to help reduce inflammation and the occurrence of exacerbations. Insmed acquired the license for the treatment from AstraZeneca in 2016.
How does Brensocatib work?
Researchers think that non-cystic fibrosis bronchiectasis is related to inflammation from immune cells called neutrophils. One type of protein that these cells produce is an enzyme called neutrophil elastase (NE), which is found at increased levels in sputum from people with bronchiectasis, especially during periods of exacerbations. NE is part of the immune response to bacteria, but prolonged exposure can damage lung cells.
Brensocatib is an inhibitor of dipeptidyl peptidase 1 (DPP1), which is critical to the activation of neutrophil enzymes such as NE. By inhibiting the activity of DPP1, brensocatib should reduce the amount of activated NE, and reduce inflammation.
Brensocatib in clinical trials
A Phase 2 randomized, double-blind, placebo-controlled clinical trial (NCT03218917) called WILLOW enrolled 256 patients with NCFB. Researchers placed patients randomly into three groups. Those in the first group received 10 mg of brensocatib. Those in the second group received 25 mg of the treatment. Finally, those in the third group received a matching placebo once per day for 24 weeks.
The results of the study appeared in the New England Journal of Medicine and showed an increase in the amount of time before exacerbations related to bronchiectasis. The average time to the first exacerbation was 67 days for the placebo group. It was 134 days for the 10 mg treatment group and 96 days for the 25 mg treatment group. Patients who received treatment also had reduced numbers of exacerbations during the 24-week period and showed lowered levels of NE in sputum. Patients generally tolerated the treatment well. However, there was an increase in dental and skin-related adverse events (side effects) in both groups receiving brensocatib.
Brensocatib received breakthrough therapy designation from the U.S. Food and Drug Administration in June 2020 for the treatment of NCFB.
Brensocatib also is being investigated as a potential COVID-19 treatment in the U.K. through a trial called Superiority Trial Of Protease inhibition in COVID-19 (STOP-COVID19).
Last updated: Sept. 29, 2020
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