Promixin (colistimethate sodium inhaled) / Zambon - LARVOL DELTA

Inhaled colistimethate sodium in patients with bronchiectasis and Pseudomonas aeruginosa infection: results of PROMIS-I and PROMIS-II, two randomised, double-blind, placebo-controlled phase 3 trials assessing safety and efficacy over 12 months. (PubMed, Lancet Respir Med) - P3 | "The data from PROMIS-I suggest a clinically important benefit of colistimethate sodium delivered via the I-neb adaptive aerosol delivery system in patients with bronchiectasis and P aeruginosa infection. These results were not replicated in PROMIS-II, which was affected by the COVID-19 pandemic and prematurely terminated."

Journal • P3 data • Bronchiectasis • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

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 (Businesswire) - P3 | N=377 | PROMIS-I (NCT03093974) | P3 | N=287 | PROMIS II (NCT03460704) |Sponsor: Zambon SpA | "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 primary efficacy endpoint was the annual pulmonary exacerbation rate....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....The PROMIS-II study had to be stopped prematurely due to the COVID-19 pandemic and the results were not satisfactory."

P3 data • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis

PROMIS-2: Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium. (clinicaltrials.gov) - P3 | N=287 | Terminated | Sponsor: Zambon SpA | Completed ➔ Terminated; The study was brought to an early close in March 2022 due to major ongoing recruitment issues primarily related to the COVID-19 pandemic and concerns regarding the continued randomization and exposure of subjects to placebo in the study.

Trial termination • Bronchiectasis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Zambon Presents Results from the Two Phase 3 PROMIS Studies of CMS I-neb in Patients with Non-Cystic Fibrosis Bronchiectasis at World Bronchiectasis Conference 2023 (PRNewswire) - P3 | N=377 | PROMIS-I (NCT03093974) | P3 | N=287 | PROMIS II (NCT03460704) |Sponsor: Zambon SpA | "Zambon...announced the final results from the Phase 3 PROMIS-I and PROMIS-II studies...PROMIS-I 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....The annual exacerbation rate (AER) 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 overall PROMIS-II study did not meet its primary endpoint, with AER of 0.89 for CMS vs 0.89 for placebo (RR: 1.00 [95% CI 0.75, 1.35] p=0.979)."

P3 data • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis

PROMIS-2: Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium (PROMIS II) (clinicaltrials.gov) - P3 | N=287 | Completed | Sponsor: Zambon SpA | Active, not recruiting ➔ Completed

Trial completion • Bronchiectasis • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

Zambon Announces Attendance at American Thoracic Society (ATS) 2022 Annual Meeting (PRNewswire) - "Zambon...today announced that the Company will attend the American Thoracic Society (ATS) 2022 Annual Meeting being held May 13 - 18, 2022 in San Francisco, CA. Zambon representatives will be at booth #10 in the ATS 2022 Clinical Trials Awareness Area to discuss advancements in the Company's two Phase 3 development programs for the treatment of non-cystic fibrosis bronchiectasis (NCFB) and bronchiolitis obliterans syndrome (BOS), two severe respiratory diseases with high unmet medical needs....The Phase 3 PROMIS-I and PROMIS-II trials will provide important evidence to help further characterize the potential clinical and quality of life benefits of CMS I‑neb® as a treatment option for patients with this devastating disease, if approved. With the PROMIS-II trial now complete, we look forward to reporting results from this important clinical program very soon."

P3 data • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis

Zambon Receives U.S. FDA Breakthrough Therapy Designation for CMS I-neb in Patients with Non-Cystic Fibrosis Bronchiectasis (NCFB) (PRNewswire) - "Zambon...today announced that the U.S. 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 adult patients with non-cystic fibrosis bronchiectasis (NCFB) colonized with P. aeruginosa....The Breakthrough Therapy Designation is supported by data from the Phase 3 PROMIS - I study..."

Breakthrough therapy designation • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis

PROMIS-2: Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium (PROMIS II) (clinicaltrials.gov) - P3; N=287; Active, not recruiting; Sponsor: Zambon SpA; Recruiting ➔ Active, not recruiting; N=420 ➔ 287; Trial completion date: Nov 2021 ➔ Feb 2022; Trial primary completion date: Nov 2021 ➔ Feb 2022

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Cystic Fibrosis • Fibrosis • Genetic Disorders • Immunology • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases

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 (Businesswire) - P3, N=377; PROMIS-I (NCT03093974); Sponsor: Leading BioSciences, Inc; "Zambon...is pleased to announce the final results from the Phase 3 PROMIS-I study...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....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 0.43-0.81, p=0.00074)."

P3 data • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases

PROMIS-2: Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium (PROMIS II) (clinicaltrials.gov) - P3; N=420; Recruiting; Sponsor: Zambon SpA; Trial completion date: Jul 2020 ➔ Nov 2021; Trial primary completion date: Jul 2020 ➔ Nov 2021

Clinical • Trial completion date • Trial primary completion date • Fibrosis • Genetic Disorders • Immunology • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases