FDA Grants Priority Review to Brensocatib for Treatment of Bronchiectasis

The FDA has accepted a new drug application (NDA) and granted priority review to brensocatib (INS1007; Insmed Inc). It has a Prescription Drug User Fee Act target date of August 12, 2025, and if approved, it will be the first and only FDA-approved treatment for bronchiectasis and the first within a new class of medicines, dipeptidyl peptidase 1 (DPP1) inhibitors, which are meant to treat neutrophil-mediated diseases.¹

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Brensocatib is an investigational small molecule reversible inhibitor of DPP1 that is administered orally to patients with bronchiectasis, chronic rhinosinusitis without nasal polyps, and hidradenitis suppurativa, as well as other neutrophil-mediated diseases. Evidence shows that the enzyme DPP1 activates neutrophil serine proteases, such as neutrophil elastase, in neutrophils when they are formed in the bone marrow. Although it has yet to be approved, brensocatib may decrease the damaging effects of inflammatory diseases, such as bronchiectasis, by inhibiting DPP1 and its activation of neutrophil serine proteases.¹

The NDA, according to experts, is based on data from the landmark phase 3 ASPEN study (NCT04594369)². The trial was a randomized, double-blind, placebo-controlled study conducted to assess the efficacy, safety, and tolerability of brensocatib compared with placebo in patients with non-cystic fibrosis bronchiectasis. Additionally, patients were enrolled if they had bronchiectasis symptoms (eg, cough, chronic sputum production, and/or recurrent respiratory infections), a radiologically confirmed diagnosis, and 2 or more exacerbations in the 12 months prior to enrollment. Demographics, disease severity, lung function, quality of life, and Pseudomonas aeruginosa status were all collected at baseline.^1-3

A total of 1682 patients were enrolled (median age: 61.3 years; 64.7% were female) from December 2020 to March 2023 and randomly assigned to receive either brensocatib (10 mg or 25 mg administered orally) or a matching placebo for 52 weeks. The findings demonstrated that both doses of brensocatib met their primary end point, achieving both statistical and clinical significance for the reduction in the annualized rate of pulmonary exacerbations compared with placebo. Additionally, both doses met multiple prespecified exacerbation-related secondary end points, including significantly prolonging the time to first exacerbation and significantly increasing the odds of remaining exacerbation-free during the 52-week treatment period.^1-3

Further, patients who were treated with 25 mg of brensocatib also demonstrated a significantly lower lung function decline at the 52-week point. Overall, brensocatib was well-tolerated in the study, with treatment-emergent adverse events (AEs) occurring in approximately 5.0% of patients treated with either dose and were more frequent than in the placebo group. These AEs included the following for 10 mg, 25 mg, and placebo, respectively: COVID-19 infection (15.8%, 20.9%, 15.8%), nasopharyngitis (7.7%, 6.3%, 7.6%), cough (7.0%, 6.1%, 6.4%), and headache (6.7%, 8.5%, and 6.9%).¹

“Bronchiectasis is a chronic, progressive disease with no approved treatments, leaving hundreds of thousands of people in the US without an effective way to reduce the pulmonary exacerbations that can lead to serious consequences," Martina Flammer, MD, MBA, chief medical officer of Insmed, said in a news release. "Brensocatib has the potential to transform the treatment landscape for bronchiectasis… We look forward to working with the FDA throughout the review process and, pending approval, bringing the first-ever bronchiectasis treatment to patients as quickly as possible.”¹

REFERENCES

1. PR Newswire. FDA Grants Priority Review to Insmed's Brensocatib for Treatment of Bronchiectasis with PDUFA Target Action Date Set for August 12, 2025. News release. February 6, 2025. Accessed February 6, 2025. https://www.prnewswire.com/news-releases/fda-grants-priority-review-to-insmeds-brensocatib-for-treatment-of-bronchiectasis-with-pdufa-target-action-date-set-for-august-12-2025-302369466.html

2. A Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib in Participants With Non-Cystic Fibrosis Bronchiectasis (ASPEN). ClincialTrials.gov identifier: NCT04594369. Updated November 12, 2024. Accessed February 6, 2025. https://clinicaltrials.gov/study/NCT04594369

3. Chalmers JD, Burgel PR, Daley CL, et al. Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics. ERJ Open Res. 2024;10(4):00151-2024. Published 2024 Jul 22. doi:10.1183/23120541.00151-2024