Zambon Announces Publication of Phase 3 PROMIS I and II Study Results in The Lancet Respiratory Medicine Showing Efficacy Results of CMS I-neb in Patients with Non-Cystic Fibrosis Bronchiectasis Colonized with P. aeruginosa

• Inhalation of colistimethate sodium via the I-neb^® Adaptive Aerosol Delivery System (CMS I-neb) significantly reduced pulmonary exacerbations and improved quality of life in non-cystic fibrosis bronchiectasis (NCFB) patients colonized with P. aeruginosa 
• Both trials showed that CMS I-neb was generally well tolerated, with no major safety concerns, and bronchospasm occurred in fewer than 5% of patients 
• Zambon is continuing to work with regulatory authorities with the goal of making colistimethate sodium delivered via a customized inhalation device available to patients with bronchiectasis and P. aeruginosa chronic infection 

Zambon, a multinational pharmaceutical company focused on innovating cure and care to improve people’s health and the quality of patients’ lives, today announced the online publication of its Phase 3 PROMIS-I and PROMIS-II studies in The Lancet Respiratory Medicine journal. The PROMIS studies assessed the efficacy and safety of inhaled colistimethate sodium administered via the I-neb^® Adaptive Aerosol Delivery System (“CMS I-neb”) as a treatment to reduce the frequency of pulmonary exacerbations in patients with Non-Cystic Fibrosis Bronchiectasis (NCFB) chronically colonized with P. aeruginosa over 12 months, compared to placebo.  

“The publication of these pivotal data in The Lancet Respiratory Medicine represents an important milestone in our commitment to developing innovative therapies for patients with severe respiratory diseases,” said Paola Castellani, Chief Medical Officer and R&D Head at Zambon. “For patients with NCFB, a condition with no approved treatment options, the results from the PROMIS program highlight the potential of CMS I-neb to improve outcomes and quality of life. We look forward to working with regulatory authorities on a path to making this important treatment available to patients as quickly as possible." 

Chronic infection with P. aeruginosa is associated with more severe disease, accelerated lung function decline, increased exacerbations, hospitalizations and a higher mortality rate.ⁱ The PROMIS trials represent the first large-scale, double-blind, placebo-controlled studies of inhaled colistimethate sodium, a widely used antibiotic in Europe for Cystic Fibrosis.  

The published study results are based upon the two global Phase 3, multicenter, randomized, double-blind, placebo-controlled PROMIS-I and PROMIS-II trials in adult patients with bronchiectasis chronically colonized with P. aeruginosa with a history of at least two exacerbations requiring oral antibiotics or one requiring intravenous antibiotics in the previous year. Patients were randomized (377 in PROMIS-I and 287 in PROMIS-II) to receive inhaled colistimethate sodium or placebo via the I-neb device twice daily for up to 12 months. The primary efficacy endpoint was the annual pulmonary exacerbation rate. Key secondary efficacy endpoints were time to first exacerbation, quality of life, change in P. aeruginosa density, severe exacerbation rate, and time to first severe exacerbation.  

Key Findings from PROMIS-I and PROMIS-II: 

• In the PROMIS-I trial, the primary endpoint of a significant reduction in annual pulmonary exacerbation rate was achieved, with a 39% reduction in exacerbations (rate ratio 0.61; 95% CI 0.46–0.82; p=0.0010) compared with placebo. 
• Severe exacerbations were reduced by 59%, and patients treated with CMS I-neb experienced a clinically importantⁱⁱ improvement in quality of life, as measured by the St. George’s Respiratory Questionnaire, and a reduction of P. aeruginosa density.  
• The PROMIS-II study had to be stopped prematurely due to the COVID-19 pandemic and the results were not satisfactory. However, when a sub analysis of the PROMIS-II pre-pandemic period was done, the results were consistent with those obtained in the PROMIS-I trial.  
• Both trials reported good tolerability, with no major safety issues identified. Bronchospasm was rare, occurring in less than 5% of patients. 

“The results of the PROMIS program represent an important breakthrough for patients with NCFB, a population that has long suffered from chronic respiratory infections without any approved treatments. For the first time, we have robust evidence showing that CMS I-neb can significantly reduce exacerbations and improve quality of life in patients with NCFB and chronic P. aeruginosa infection, offering hope where there were previously limited options,” said Dr. Charles Haworth, Respiratory Physician at the Cambridge Centre for Lung Infection at Royal Papworth Hospital, and PROMIS trials Chief Investigator. 

“These findings underscore the importance of inhaled antibiotics, such as CMS I-neb, in reducing exacerbations and improving outcomes in patients with NCFB chronically infected with P. aeruginosa. Chronic bronchial infection plays a key role in driving inflammation and airway damage in bronchiectasis, and reducing exacerbations has been linked to better prognosis, quality of life and lung function,” said Professor James Chalmers, Professor of Respiratory Research at the University of Dundee and PROMIS Investigator. 

The PROMIS clinical program has received FDA Qualified Infectious Disease Product (QIDP), Fast Track and Breakthrough designations for the reduction in the incidence of pulmonary exacerbations in adult NCFB patients colonized with P. aeruginosa.