Zambon Publishes Phase 3 PROMIS I and II Results on CMS I-neb Efficacy in Non-Cystic Fibrosis Bronchiectasis in The Lancet

Inhalation of colistimethate sodium via the I-neb® Adaptive Aerosol Delivery System significantly reduced pulmonary exacerbations and enhanced the quality of life for patients with non-cystic fibrosis bronchiectasis (NCFB) colonized with P. aeruginosa. Both clinical trials demonstrated that CMS I-neb was generally well-tolerated, with bronchospasm occurring in fewer than 5% of patients. Zambon is working with regulatory bodies to make this treatment available to patients.

Zambon, a global pharmaceutical firm, reported the publication of its Phase 3 PROMIS-I and PROMIS-II studies in The Lancet Respiratory Medicine journal. These studies evaluated the effectiveness and safety of inhaled colistimethate sodium delivered through the I-neb® Adaptive Aerosol Delivery System (CMS I-neb) in reducing pulmonary exacerbations in NCFB patients colonized with P. aeruginosa over a 12-month period, compared to a placebo.

Paola Castellani, Chief Medical Officer and R&D Head at Zambon, highlighted the significance of these findings, stating that the PROMIS program underscores the potential of CMS I-neb to improve outcomes and quality of life for patients with NCFB, a condition with no approved treatments. She emphasized Zambon's dedication to working with regulatory authorities to expedite the availability of this treatment.

Chronic infection with P. aeruginosa is linked to more severe disease, faster lung function decline, increased exacerbations, hospitalizations, and a higher mortality rate. The PROMIS trials are the first large-scale, double-blind, placebo-controlled studies of inhaled colistimethate sodium, a commonly used antibiotic in Europe for NCFB.

The study results come from two global Phase 3 trials, PROMIS-I and PROMIS-II, involving adult patients with bronchiectasis chronically colonized with P. aeruginosa who had 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, with secondary endpoints including time to first exacerbation, quality of life, change in P. aeruginosa density, severe exacerbation rate, and time to first severe exacerbation.

Key findings from the PROMIS-I and PROMIS-II trials include:

1. PROMIS-I achieved a significant reduction in the annual pulmonary exacerbation rate, with a 39% reduction in exacerbations compared to placebo. Severe exacerbations were reduced by 59%, and patients treated with CMS I-neb showed a clinically important improvement in quality of life and a reduction in P. aeruginosa density.
2. PROMIS-II had to be halted prematurely due to the COVID-19 pandemic, leading to unsatisfactory results. However, a sub-analysis of the pre-pandemic period showed results consistent with those of PROMIS-I.
3. Both trials reported good tolerability, with no major safety concerns and rare occurrence of bronchospasm (less than 5%).

The PROMIS program marks a significant breakthrough for NCFB patients, who have long suffered from chronic respiratory infections without any approved treatments. Dr. Charles Haworth from the Cambridge Centre for Lung Infection at Royal Papworth Hospital emphasized the robust evidence supporting CMS I-neb's ability to reduce exacerbations and improve quality of life in this patient population.

Professor James Chalmers from the University of Dundee noted the importance of inhaled antibiotics like CMS I-neb in reducing exacerbations and improving outcomes for NCFB patients chronically infected with P. aeruginosa. He highlighted that chronic bronchial infection drives inflammation and airway damage in bronchiectasis, and reducing exacerbations can lead to better prognosis, quality of life, and lung function.

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

Bronchiectasis, characterized by recurrent infection, inflammation, persistent cough, and sputum production, is a growing global health issue. The condition's progression is primarily determined by the rate of exacerbations, many of which are related to Pseudomonas aeruginosa. Treating this infection remains a clinical priority, with the primary goals being to prevent exacerbations, reduce symptoms, improve quality of life, and halt disease progression. The prevalence of NCFB has increased significantly over the past decade, with the incidence rising particularly among women and older individuals.

Colistimethate sodium (CMS) is a pro-drug form of the antibiotic colistin, effective against aerobic Gram-negative pathogens like P. aeruginosa. As one of the last therapeutic options against multi-drug-resistant Gram-negative bacteria, CMS remains a crucial tool in treating severe infections.

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