Positive Results from Phase 3 PROMIS-I Study of CMS I-neb® in Patients with Non-Cystic Fibrosis Bronchiectasis Presented at European Respiratory Society (ERS) Annual Meeting
- Data shows inhalation via the I-neb ® Adaptive Aerosol Delivery System of colistimethate sodium (CMS) results in reduction of pulmonary exacerbations in non-cystic fibrosis bronchiectasis (NCFB) patients compared to placebo
- The primary endpoint was met, the annual rate of exacerbations was significantly lower in patients receiving CMS I-neb ® vs placebo (0.58 per patient per year vs 0.95, rate ratio (RR) 0.61 95% CI 0.46-0.82, p=0.00101)
- Treatment has been granted FDA QIDP and Fast Track designations
Zambon, a pharmaceutical company on a mission to innovate cure & care to make patients’ lives better, is pleased to announce the final results from the Phase 3 PROMIS-I study, which were presented at the European Respiratory Society Congress today.
The study, which examined the use of CMS powder for nebulizer solution, delivered by the I-neb ® AAD system (hereafter referred to as “CMS I-neb ® ”) for the prevention of pulmonary exacerbations in patients with NCFB, showed CMS I-neb ® significantly reduced the annual rate of exacerbations and severe exacerbations in patients with NCFB and Pseudomonas aeruginosa chronic infection and prolonged the time to first exacerbation compared to placebo, also improving Quality of Life (QoL). The treatment was demonstrated to be well tolerated.
In patients with non-cystic fibrosis bronchiectasis, lung infection with P. aeruginosa is associated with frequent pulmonary exacerbations and admission to hospital for treatment, reduced quality of life, and increased mortality (1) . Currently there is no approved therapy for the disease.
The data were presented at the 9.30am CEST clinical trials session, ALERT: bronchiectasis and COVID’ under the abstract 31109/3979:The efficacy and safety of colistimethate sodium delivered via the I-neb ® in bronchiectasis: the PROMIS-I randomized controlled trial.
The trial explored the effect of CMS I-neb ® on the frequency of pulmonary exacerbations in NCFB patients chronically infected with P. aeruginosa. The trial met its primary endpoint, demonstrating that use of CMS I-neb ® twice-daily resulted in a statistically significant reduction of pulmonary exacerbations over the course of the 12-month study. A total of 377 patients were randomized, 177 to CMS I-neb ® and 200 to placebo. The annual rate of exacerbations was significantly lower in patients receiving CMS I-neb ® vs placebo (0.58 per patient per year vs 0.95, rate ratio (RR) 0.61 95% CI 0.46-0.82, p=0.00101). The treatment effect was even larger in adherent subjects (43.5% reduction in exacerbations, p= 0.00080). The trial also met important secondary endpoints, demonstrating improvements compared to placebo with prolonged time to first exacerbation in the CMS I-neb ® group (HR 0.59, 95% CI 0.430.81, p=0.00074). The frequency of severe exacerbations was also reduced (RR 0.41 95% CI 0.23-0.74, p=0.00300). Quality of life measured by the St. George’s Respiratory Questionnaire (SGRQ) significantly improved in CMS I-neb ® arm with 4.55 point difference vs placebo after 12 months treatment (p=0.0055). After 28 days treatment, P. aeruginosa density was significantly reduced in the treatment arm, p < 0.00001). The percentage of patients with adverse events was similar between groups. Bronchospasm and antibiotic resistance were infrequently observed (2.8% and 1% respectively).
“The PROMIS-I data show that CMS taken twice daily through the I-neb ® reduces exacerbation frequency and improves quality of life in people with bronchiectasis and chronic P. aeruginosa infection,” said Dr. Charles Haworth, Respiratory Physician at the Cambridge Centre for Lung Infection at Royal Papworth Hospital, and PROMIS-I Chief Investigator. “The data also demonstrate that 12 months treatment is well tolerated. These results are encouraging for patients as there is currently no approved drug treatment for this indication.”
NCFB has a progressive course primarily determined by the rate of exacerbations, many of which are related to P. aeruginosa. Consequently, research efforts directed to treat infection by P. aeruginosa and its associated acute exacerbations remain a clinical priority (2) .
“We would like to extend our sincere gratitude to all of the patients and study centers for their collaboration throughout PROMIS-I,” said Paola Castellani, CMO and R&D Head at Zambon. “We are delighted to see that the hard work and commitment from all parties has paid off and provided us with encouraging data. We hope that these data will prove to be an important step as we seek a much-needed treatment to manage NCFB.”
The PROMIS clinical program has received FDA Qualified Infectious Disease Product (QIDP) and Fast Track designation for the prevention of pulmonary exacerbations in adult NCFB patients with P. aeruginosa.
“At Zambon, we are committed to developing treatments for severe respiratory diseases with limited treatment options,” said Roberto Tascione, CEO at Zambon. “This trial is testament to our growing credibility in this area, representative of our drive for innovation and creates a strong foundation upon which we can continue to grow and provide needed medicines to improve patients’ lives. With a number of our other mid- and late-stage trials in respiratory diseases ongoing, we are encouraged by the positive data of PROMIS-I which we hope is the first of many successes.”
There are no approved inhaled treatments currently available for patients with bronchiectasis and P. aeruginosa infection; Zambon, together with its long-standing partner Xellia, will continue to actively work in strict collaboration, in order to make the drug approved across the globe.
1. Finch S, McDonnell MJ, Abo-Leyah H, Aliberti S, Chalmers JD. A Comprehensive Analysis of the Impact of Pseudomonas aeruginosa Colonization on Prognosis in Adult Bronchiectasis. Ann Am Thorac Soc Vol 12, No 11, pp 1602–1611, Nov 2015
2. Severiche-Bueno D, Gamboa E, Reyes LF, Chotirmall SH. Hot topics and current controversies in non-cystic fibrosis bronchiectasis. Breathe 2019; 15: 286–295