Cystic fibrosis (CF) and non-cystic fibrosis bronchiectasis (NCFBE) are two distinct respiratory conditions that share a common denominator: bronchiectasis, characterized by the dilation and damage of the airways. However, these conditions differ fundamentally in their underlying causes and necessitate different management approaches. Cystic fibrosis is a genetic disorder caused by CFTR gene mutations, resulting in thick mucus obstructing airways, leading to recurrent lung infections and bronchiectasis. CF management targets CFTR dysfunction with specialized therapies. On the other hand, non-cystic fibrosis bronchiectasis (NCFBE) has diverse causes, like infections or immune issues. It is treated by addressing underlying factors with bronchodilators, antibiotics, and airway clearance techniques despite sharing symptoms with CF. DelveInsight’s Cystic Fibrosis – Market Insight, Epidemiology, and Market Forecast – 2032 estimated that 67,000 individuals were afflicted by CF in 2022. The increase in cystic fibrosis cases underscores the urgent need for innovative therapies as medical advancements have prolonged the lives of CF patients, creating a greater demand for treatments to manage the condition’s long-term effects. Developing novel therapies can address the evolving healthcare requirements of this growing patient population.

Insmed Inc.’s creation, Brensocatib, a small oral molecule acting as a reversible inhibitor of dipeptidyl peptidase 1 (DPP1), holds substantial promise for patients with both CF and NCFBE. DPP1 is an enzyme accountable for triggering neutrophil serine proteases (NSPs) in neutrophils, pivotal white blood cells central to infection defense and inflammation regulation. Brensocatib’s mode of operation centers on DPP1 inhibition, effectively mitigating the harmful consequences of excessive NSPs in inflammatory conditions such as CF.

A significant breakthrough in the development of Brensocatib was unveiled at the European Respiratory Society (ERS) International Congress 2023, held in Milan, Italy. The conference featured a presentation on the pharmacokinetics and safety of Brensocatib in patients with cystic fibrosis, a pivotal moment for those battling this condition. The presentation showcased the results of a multiple-dose pharmacokinetic/pharmacodynamic study of Brensocatib in CF patients. This Phase II study included patients on background CFTR modulator drugs and those without. Over approximately one month, CF patients were dosed with a placebo, 10 mg, 25 mg, and 40 mg of Brensocatib.

The study’s findings revealed a clear dose-dependent and exposure-dependent inhibition of blood NSPs in patients treated with Brensocatib across all doses, consistent with its mechanism of action. Notably, safety and tolerability mirrored previous observations in the Phase II WILLOW study, with no significant drug-related concerns. Based on these promising results and insights from prior WILLOW and ASPEN studies, there was a consensus that further evaluation of a 65 mg dose of Brensocatib was unnecessary for this patient population. This suggests that Brensocatib could be a promising treatment option for CF patients, offering hope for improved quality of life.

Standard CF management often includes a comprehensive regimen to reduce symptom severity and improve lung function. This all-encompassing approach includes many components like airway clearance procedures, nutritional assistance, and drugs like bronchodilators and antibiotics for infection treatment. CFTR modulator drugs like ivacaftor and tezacaftor/ivacaftor can target the underlying genetic problem and alleviate CF-related symptoms when certain genetic mutations are present. DelveInsight’s Cystic Fibrosis – Market Insight, Epidemiology, and Market Forecast – 2032 estimated the current market size of CF to be around USD 8,000 million in 2022.

The ERS International Congress 2023 marked a pivotal moment in the journey of Brensocatib, offering hope and new possibilities for individuals affected by cystic fibrosis and non-cystic fibrosis bronchiectasis. With its innovative mechanism of action and promising results, Brensocatib may become a beacon of hope for patients worldwide, ushering in a brighter future in battling these challenging respiratory conditions.