Zambon said that the Phase 3 PROMIS-II trial of its CMS I-neb inhaled dry powder colistimethate sodium for the treatment of non-cystic fibrosis bronchiectasis (NCFB) in adult patients with chronic P. aeruginosa lung infections failed to meet its primary endpoint due to disruptions caused by the COVID-19 pandemic; those disruptions also resulted in the early termination of the study.
The company, which previously reported that the PROMIS-I trial of CMS I-neb met its primary endpoint as well as several secondary endpoints, says that overall, the PROMIS program supports the use of CMS for this indication. CMS I-neb received Fast Track and QIDP designations for the treatment of NCFB in in patients with chronic P. aeruginosa infections in 2018. The FDA granted the product Breakthrough Therapy designation in 2022.
According to Zambon, PROMIS-II data gathered prior to the official beginning of the pandemic showed a significant reduction in annual exacerbation rate for patients using CMS I-neb compared to those using a placebo; however, data gathered during the pandemic demonstrated a greater exacerbation rate for CMS I-neb. Taken all together, the data showed no difference in the reduction of the exacerbation rate between CMS I-neb and placebo. However, the company says, the decrease in P. aeruginosa sputum density in the CMS I-neb group was “consistent with those obtained in PROMIS-I and the preceding Phase 2 trial.”
Zambon Chief Medical Officer and R&D Head Paola Castellani commented, “We would like to extend our sincere gratitude to all of the patients and study centers for their collaboration throughout the PROMIS trials program. Results of PROMIS-II were unexpected in light of the positive data seen in PROMIS-I and the Phase 2 trial. Unfortunately, PROMIS-II was predominantly conducted during the COVID-19 pandemic, with more than 50 percent of the visits during the pandemic period, in contrast to PROMIS-I which was performed almost completely before the pandemic. The unprecedented COVID-19 pandemic fundamentally changed the environment in which the trial was conducted, with marked changes in patient behavior, the significant drop of background rate of exacerbations and trial conduct. The post-hoc analyses provided helpful insights into the possible underlying causes for the inconsistent results and demonstrated that, pre-pandemic, the benefit of CMS on annualized exacerbation rate was consistent with PROMIS-I.”
Zambon CEO Ilaria Villa said, “With no approved drugs for patients with NCFB colonized by P. aeruginosa anywhere in the world, the completion of the Phase 3 PROMIS clinical trial program marks an important step forward in support of our mission to develop and provide treatment options for people with rare and severe respiratory diseases. We look forward to working with the FDA over the coming months with the hope of bringing much needed benefit to patients whose lives are severely impacted by this disease.”
Read the Zambon press release.
