Phase 3 Trial Testing Brensocatib for Bronchiectasis Set to Start Soon

Phase 3 Trial Testing Brensocatib for Bronchiectasis Set to Start Soon

A global Phase 3 clinical trial of brensocatib in people with non-cystic fibrosis (CF) bronchiectasis is expected to launch by the end of this year, according to the treatment’s developer Insmed.

Insmed announced the design for the upcoming ASPEN trial and outlined plans to develop the therapy in other neutrophil-mediated diseases during the company’s virtual Research & Development Day on Sept. 30.

“We believe brensocatib, our DPP1 inhibitor, offers an entirely new approach to address a wide array of neutrophil-mediated diseases. We plan to build upon our early leadership position in this space with our anticipated near-term registrational study in [non-CF bronchiectasis, followed by a new development program in cystic fibrosis and plans to explore other opportunities,” Will Lewis, chairman and CEO of Insmed, said in a press release.

ASPEN’s design was developed with input from the U.S. Food and Drug Administration and the European Medicines Agency, according to Insmed.

The trial, which is intended to provide data to support regulatory approval, will consist of a screening period of up to six weeks, followed by a one-year treatment period, and four weeks off treatment. During screening, participants will be classified by geographic location, presence of Pseudomonas aeruginosa, and the number of exacerbations — or sudden worsening of symptoms — in the previous year.

The study is expected to have 1,620 participants who will be randomly assigned to receive once-daily oral doses of 10 mg of brensocatib, 25 mg of brensocatib, or a placebo for the duration of the treatment period. The trial will be carried out at roughly 480 sites in 36 countries.

ASPEN’s goal is to determine if brensocatib reduces the rate of pulmonary exacerbations and increases the time to first exacerbation, the proportion of patients who remain free of exacerbations over the treatment period, and the volume of air a patient can exhale from the lungs in one second — forced expiratory volume in one second.

Brensocatib, an oral small molecule, was originally developed by AstraZeneca before being licensed to Insmed in 2016.

In non-CF bronchiectasis, immune cells called neutrophils are activated by the protein dipeptidyl peptidase 1 (DPP1) and release enzymes that damage the lungs. Brensocatib acts by blocking DPP1 and preventing neutrophil activation. 

In a Phase 2 trial called WILLOW (NCT03218917), treatment with brensocatib reduced the risk and rate of exacerbations in adults with non-CF bronchiectasis, regardless of patient age or clinical history. Earlier this year, brensocatib was granted breakthrough therapy designation by the FDA based on results from the 24-week WILLOW study.