The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to colistimethate sodium powder for nebulization solution (CMS I–neb®) for the reduction in the incidence of pulmonary exacerbations in adults with non-cystic fibrosis bronchiectasis (NCFB) colonized with P. aeruginosa.
The CMS powder is a prodrug of colistin, a polymyxin antibiotic derived from Bacillus polymyxa var. colistinus. The investigational treatment is delivered by the I–neb®Adaptive Aerosol Delivery system, which delivers a precise, reproducible dose of the drug only when the patient inhales (not continuously like other nebulizers).
The designation was supported by data from the multicenter, double-blind, placebo-controlled phase 3 PROMIS-I study (ClinicalTrials.gov Identifier: NCT03093974), which evaluated the efficacy and safety of CMS I–nebin reducing the incidence of pulmonary exacerbations in adults with NCFB colonized with P. aeruginosa. Patients were randomly assigned to receive either CMS I–neb (n=177) or placebo (n=200) inhaled twice daily for 12 months.
Results showed that treatment with CMS I–neb met the primary endpoint demonstrating a significant reduction in the annual rate of pulmonary exacerbations over 12 months compared with placebo (0.58 vs 0.95 per patient per year, respectively; rate ratio [RR], 0.61; 95% CI, 0.46-0.82; P =.001).
Compared with placebo, treatment with CMS I–neb also significantly prolonged the time to first exacerbation (hazard ratio, 0.59; 95% CI, 0.43-0.81; P =.00074), reduced the frequency of severe exacerbations (RR 0.41; 95% CI, 0.23-0.74; P =.003), and improved quality of life (as measured by the St. George’s Respiratory Questionnaire; P =.0055). Similar adverse events were observed between the treatment and placebo arms.
“With no approved drugs for patients with NCFB colonized by P. aeruginosa anywhere in the world, the Breakthrough Therapy designation by FDA marks an important step forward in support of our mission to develop and provide treatment options for people with rare and severe respiratory diseases,” said Roberto Tascione, CEO at Zambon. “We are proud that the FDA has recognized the importance of CMS I–neb® and the urgent need to develop innovative treatments for these patients.”
- Zambon receives US FDA Breakthrough Therapy designation for CMS I-neb® in patients with non-cystic fibrosis bronchiectasis (NCFB). News release. Zambon S.p.A. Accessed April 21, 2022. https://www.prnewswire.com/news-releases/zambon-receives-us-fda-breakthrough-therapy-designation-for-cms-i-neb-in-patients-with-non-cystic-fibrosis-bronchiectasis-ncfb-301530011.html
- 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. News release. Zambon S.p.A. September 8, 2021. Accessed April 21, 2022. https://www.zambon.com/en/media/press/2021-09-08-positive-results-phase-3-promis-i-study-cms-i-nebr-patients-non-cystic