Insmed presented positive results from the phase 2 WILLOW study evaluating brensocatib (formerly INS1007) in patients with non-cystic fibrosis bronchiectasis (NCFBE). Brensocatib reduced time to first pulmonary exacerbation and reduced the rate of exacerbations versus placebo. The results were presented during a virtual American Thoracic Society (ATS) session titled Breaking News: Clinical Trial Results in Pulmonary Medicine.
WILLOW was a randomized, double-blind, placebo-controlled, parallel-group, multi-center, multi-national, study to assess the efficacy, safety and tolerability, and pharmacokinetics of brensocatib administered once daily for 24 weeks in patients with non-cystic fibrosis bronchiectasis (NCFBE). The study was conducted at 116 sites and enrolled 256 adult patients diagnosed with NCFBE who had at least two documented pulmonary exacerbations in the 12 months prior to screening. Patients were randomized 1:1:1 to receive either 10 mg or 25 mg of brensocatib or matching placebo. The primary efficacy endpoint was the time to first pulmonary exacerbation over the 24-week treatment period in the brensocatib arms compared to the placebo arm.
The WILLOW study met its primary endpoint, with brensocatib significantly prolonging time to first pulmonary exacerbation over the 24-week treatment period versus placebo. The risk of exacerbation at any time during the trial was reduced by 42% for the 10 mg group versus placebo and by 38% for the 25 mg group versus placebo. Treatment with brensocatib 10 mg also resulted in a significant reduction in the rate of pulmonary exacerbations, a key secondary endpoint, versus placebo. Patients treated with brensocatib experienced a 36% reduction in the 10 mg arm and a 25% reduction in the 25 mg arm versus placebo. The most common AEs in patients treated with brensocatib were cough, headache, sputum increase, dyspnea, infective exacerbation of bronchiectasis, diarrhea, fatigue, and upper respiratory tract infection.
Brensocatib received breakthrough therapy designation from the U.S. Food and Drug Administration in June 2020 for the treatment of adult patients with NCFBE for reducing exacerbations.
Insmed plans to initiate a Phase 3 program for brensocatib in bronchiectasis in the second half of 2020.
About brensocatib (formerly INS1007)
Brensocatib (formerly INS1007) is a small molecule, oral, reversible inhibitor of dipeptidyl peptidase I (DPP1). DPP1 is an enzyme responsible for activating neutrophil serine proteases (NSPs), such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation. In chronic inflammatory lung diseases, neutrophils accumulate in the airways and result in excessive active NSPs that cause lung destruction and inflammation. Brensocatib may decrease the damaging effects of inflammatory diseases such as bronchiectasis by inhibiting DPP1 and its activation of NSPs.
About Non-cystic fibrosis bronchiectasis (NCFBE)
NCFBE is a severe, chronic pulmonary disorder in which the bronchi become permanently dilated due to a cycle of infection, inflammation, and lung tissue damage. Symptoms include chronic cough, excessive sputum production, shortness of breath, and repeated respiratory infections, which can worsen the underlying condition. NCFBE affects approximately 340,000 to 520,000 patients in the U.S. There are no approved therapies specifically targeting NCFBE in the U.S., Europe, or Japan.