Brensocatib slows lung function decline, improves quality of life in bronchiectasis

Key takeaways:

• New endpoints from the ASPEN trial were presented at the World Bronchiectasis Conference.
• FDA new drug application submission plans are set to take place in the last quarter of this year.

Patients with non-cystic fibrosis bronchiectasis experienced less FEV₁ and FVC decline and had improved quality of life with 52-week once-daily brensocatib vs. placebo, according to findings presented at the World Bronchiectasis Conference.

“The FVC data are an important addition to the already reported FEV₁ data,” James D. Chalmers, MBChB, PhD, professor and consultant respiratory physician at the University of Dundee School of Medicine in the United Kingdom, told Healio. “The FEV₁ data suggest that treatment with brensocatib 25 mg daily slowed the rate of decline in lung function. The FVC data suggest a very clear slowing of the decline of FVC, particularly with the 25 mg dose.”

In the phase 3, global, randomized, double-blind, placebo-controlled ASPEN trial, the intent-to-treat population included 1,680 adults and 41 adolescents with non-cystic fibrosis bronchiectasis. Chalmers and colleagues determined the efficacy of once-daily 10 mg brensocatib (Insmed; n = 583) and 25 mg brensocatib (n = 575) vs. placebo (n = 563) at 52 weeks.

Healio previously reported on topline results from this trial in June, which revealed that once-daily brensocatib for 52 weeks lowered the annualized pulmonary exacerbation rate and was well tolerated.

By the 52-week mark, patients receiving 10 mg brensocatib vs. placebo had a 21.1% reduction in the annualized rate of exacerbations (P = .0019). Researchers observed a similar significant decrease in this exacerbation rate by 19.4% when comparing patients receiving 25 mg brensocatib with those receiving placebo (P = .0046).

Additionally, both brensocatib doses vs. placebo prolonged the time to first pulmonary exacerbation (10 mg, 18.7%; P = .01; 25 mg, 17.5%; P = .0182) and raised the odds for remaining exacerbation free (10 mg, OR = 1.412; P = .0059; 25 mg, OR = 1.4; P = .0074) over the 1-year study period.

Researchers previously reported a significant difference between the 25 mg brensocatib group and the placebo group in terms of change in baseline FEV₁ at 52 weeks (38 mL; P = .0054), and this was also the case when evaluating the change in baseline FVC (75 mL; P < .0001) because the 25 mg brensocatib group experienced less loss of FVC vs. the placebo group (–12 mL vs. –87 mL).

“Taken together, these data suggest that brensocatib 25 mg may slow the progression of the disease as measured by lung function and suggest that the treatment may be disease modifying,” Chalmers told Healio.

Average daily bronchiectasis exacerbation and symptom tool (BEST) score was another new endpoint reported on at the conference.

“The BEST score is a daily diary that measures patients’ symptoms on a daily basis,” Chalmers said. “The ASPEN trial was the first bronchiectasis trial to measure daily symptoms in this way.”

Between baseline and week 52, the least-squares mean change in average daily BEST score was –0.999 among those receiving 25 mg brensocatib, which was greater than the change of –0.426 among those receiving placebo (mean difference, –0.572; P < .0001).

Notably, Chalmers told Healio these data add support to the Quality of Life-Bronchiectasis questionnaire Respiratory Symptom Domain score findings, in which patients receiving 25 mg brensocatib vs. placebo had a more improved score between baseline and 52 weeks (least-squares mean change, 8.575 vs. 4.809; mean difference, 3.766; P = .0004).

“In addition to the exacerbation benefits of brensocatib in bronchiectasis, these data support the view that brensocatib may slow the progression of the disease and may reduce patients’ symptoms,” Chalmers said. “From a patient perspective, a treatment that can potentially prevent exacerbations, reduce the risk of patients getting worse and make patients feel better on a daily basis is very important.

“There are currently no licensed treatments for bronchiectasis, so these data are very encouraging for patients,” Chalmers added.

The press release noted that there are FDA new drug application submission plans set to take place in the last quarter of this year.