Targeting the vicious vortex of bronchiectasis to improve symptoms and quality of life for patients

What is bronchiectasis?

Bronchiectasis is a chronically progressive pulmonary disease characterized by irreversible airway dilation, which can occur in patients with a range of underlying conditions. These include genetic disorders such as cystic fibrosis (CF) and primary ciliary dyskinesia (PCD), inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease, and chronic lung diseases such as asthma, chronic obstructive pulmonary disease and interstitial lung disease. However, in up to 50% of patients with bronchiectasis, no underlying condition can be identified (i.e., it is idiopathic). Irrespective of the underlying disease etiology, the pathophysiology of bronchiectasis is driven by a complex interplay of airway dysfunction, inflammation, infection and structural damage. This is termed the ‘vicious vortex’.

Symptoms of bronchiectasis

Although bronchiectasis was once considered an orphan disease, improved awareness and diagnostic methods mean that prevalence rates of up to 566 patients per 100, 000 (0.6%) have recently been reported. Most patients with bronchiectasis present with cough and production of large volumes of sputum, limiting participation in social activities and having a significant impact on their quality of life. They also experience recurrent infections and frequent exacerbations, leading to progressive lung damage, frequent hospital visits, and high treatment costs. Age-adjusted mortality for patients with bronchiectasis is more than twice that of the general population.

“I’m fighting [for] breath each time I breathe. I know that each exacerbation further damages my bronchi and lungs.” – Patient with bronchiectasis

There are no approved treatments for bronchiectasis, and current management relies on treating individual components of the disease. For example, patients may receive a short course of antibiotics to treat infection, and mucoactive drugs or physiotherapy may be used to aid airway clearance. Patients may also receive treatments for their underlying condition. These approaches do not specifically target the vicious vortex that drives bronchiectasis, underscoring the necessity to develop novel, targeted treatments.

BI 1291583 is a novel cathepsin C (CatC) inhibitor with the potential to improve symptoms and quality of life for patients with bronchiectasis. Inhibition of CatC can reduce the level of neutrophilic inflammation that plays a key role in the pathogenesis of bronchiectasis. This may allow BI 1291583 to prevent airway destruction, improve pathogen clearance, restore mucus composition, and reduce aberrant lung inflammation. BI 1291583 is an investigational drug, which has not been approved for any proposed indication by any regulatory authority including the US Food and Drug Administration. Boehringer Ingelheim is currently investigating its efficacy and safety profile.

Airleaf™ (NCT05238675) and Clairafly™ (NCT05865886) are Phase II, randomized, double-blind, placebo-controlled trials of BI 1291583 in patients with non-cystic fibrosis bronchiectasis and cystic fibrosis bronchiectasis, respectively. Airleaf™ will enroll around 240 patients with sites in >20 countries across Europe, North America and Asia. Clairafly™ will recruit approximately 24 patients across sites in six European countries and the US. On completion of the initial studies, patients will be offered continued access to BI 1291583 as part of the Clairleaf™ rollover trial (NCT05846230). Based on the Phase II study results, patients with non-cystic fibrosis bronchiectasis and cystic fibrosis bronchiectasis may be included in a ‘one’ bronchiectasis Phase III program.

Leveraging more than 100 years of BI heritage in respiratory disease across a range of conditions, we look forward to expanding our portfolio and potentially bring this innovative new treatment to people living with bronchiectasis.