Apulmiq (liposomal ciprofloxacin DR) / Savara, Grifols - LARVOL DELTA

Pseudomonas aeruginosa genetic variants associated with increased exacerbations in bronchiectasis (BTS WM 2024) - "aeruginosa was isolated from sputum from 276 patients with chronic P. aeruginosa infection in the ORBIT-3 (n=176) and ORBIT-4 (n=100) trials of inhaled liposomal ciprofloxacin (ARD-3150 n=182, placebo n=94) at baseline prior to treatment...P. aeruginosa is highly genetically diverse within bronchiectasis infections suggesting adaptations to the infection environment with potential influences on patient outcomes."

Bronchiectasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases

Sputum proteomics uncovers the heterogeneity of Pseudomonas aeruginosa infections in bronchiectasis (ERS 2024) - "Sputum was collected from patients with chronic PA infection in the ORBIT trials of inhaled liposomal ciprofloxacin (ARD-3150 n=196, placebo n=85)...IL7 was decreased in patients with >1 PE (p=0.002, ≤1 PE=0.32±0.91, >1 PE=0.076±0.13) and predicted time-to-first PE (p=0.023, HR=0.57, 95%CI=0.35-0.92). PA infections in BE have a heterogeneous inflammatory profile altered by PA abundance and microbiota diversity."

Heterogeneity • Bronchiectasis • Infectious Disease • Pulmonary Disease • Respiratory Diseases • ELANE • IL7 • MMP8

Savara Provides Pipeline and Business Update (Businesswire) - P3, N=200; NCT03181932; Sponsor: Savara Inc.; "The Company announced that the Phase 3 trial of AeroVanc (vancomycin hydrochloride inhalation powder) in people living with cystic fibrosis (CF) who have Methicillin-resistant Staphylococcus aureus (MRSA) lung infection did not meet the primary endpoint...Data from the trial showed a mean change from baseline in FEV1 percent predicted compared to placebo of 1.4 at week 4 (p=0.33), 1.3 at week 12 (p=0.33), and 3.0 at week 20 (p=0.07) in the primary analysis population of patients 6-21 years of age...Unfortunately, based on the AVAIL results, we are discontinuing further development of AeroVanc...the Company has discontinued the Apulmiq clinical development program...The Company today revised guidance on the initiation of IMPALA 2 and now expects the trial to start in Q2 2021, versus the end of Q1 2021."

Discontinued • P3 data • Trial initiation date • Cystic Fibrosis • Infectious Disease • Non‐Cystic Fibrosis Bronchiectasis

[VIRTUAL] Late Breaking Abstract - Changes in respiratory symptoms during 48 weeks treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies (ERS 2020) - "Inhaled ARD-3150 resulted in significant improvements in respiratory symptoms during the on-treatment periods which were lost during off-treatment periods."

Late-breaking abstract • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases

Savara Reports Second Quarter 2020 Financial Results and Provides Business Update (Businesswire) - "The Company is further analyzing data from the previous Apulmiq development program and is also working on the design of a future program, with inputs from external bronchiectasis experts, for future discussion with the FDA."

FDA event • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases

Changes in respiratory symptoms during 48 weeks treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies. (PubMed, Eur Respir J) - "Inhaled ARD-3150 resulted in significant improvements in respiratory symptoms during the on-treatment periods which were lost during off-treatment periods. These results supports the concept that reducing bacterial load can improve respiratory symptoms in patients with bronchiectasis."

Journal • Non‐Cystic Fibrosis Bronchiectasis • Respiratory Diseases

Safety and Tolerability of ARD-3150, Inhaled Liposomal Ciprofloxacin, in Patients with Bronchiectasis and Chronic Pseudomonas Aeruginosa Infection: Results from Two Phase 3 Trials (ATS 2018) - P3; "Conclusion ARD-3150 was well tolerated, with an AE profile similar to placebo in the 48-week trials. ARD-3150 inhalation did not produce throat or respiratory tract irritation or bronchospasm, a major concern with inhaled antibiotics in this population."

Clinical • P3 data • Biosimilar • Fibrosis • Immunology

Evaluation of liposomal ciprofloxacin formulations in a murine model of anthrax. (PubMed, PLoS One) - "If treatment was initiated 48 hours after exposure the survival rate was reduced to 46-65%. These studies suggest that lipoquin and apulmiq may be attractive therapies as PEP and as part of a treatment cocktail for B. anthracis."

Journal • Preclinical

Inhaled liposomal ciprofloxacin in patients with non-cystic fibrosis bronchiectasis and chronic lung infection with Pseudomonas aeruginosa (ORBIT-3 and ORBIT-4): two phase 3, randomised controlled trials. (PubMed, Lancet Respir Med) - P3 | "In patients with non-cystic fibrosis bronchiectasis and chronic P aeruginosa lung infection requiring antibiotic therapy in the preceding year, ARD-3150 led to a significantly longer median time to first pulmonary exacerbation compared with placebo in ORBIT-4, but not in ORBIT-3 or the pooled analysis. Inconsistency between the trials suggests further research is needed into the heterogeneity of non-cystic fibrosis bronchiectasis and optimal outcome measures for inhaled antibiotics."

Clinical • Journal • P3 data

Savara obtains global rights to develop and commercialize Apulmiq (Businesswire) - "Savara Inc….today announced the Company has entered into an exclusive license and collaboration agreement with Grifols for Apulmiq (inhaled liposomal ciprofloxacin). Also known as Linhaliq in Europe, Apulmiq is a late-stage investigational inhaled antibiotic in Phase 3 development for the treatment of non-cystic fibrosis bronchiectasis (NCFB)….Under the terms of the agreement, Savara has obtained the worldwide rights to develop and commercialize Apulmiq...The Company expects to work with regulatory agencies to plan a confirmatory Phase 3 study..."

Licensing / partnership • New P3 trial

Microbiologic changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in subjects with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection. (PubMed, Clin Microbiol Infect) - "Microbiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit."

Clinical • Journal

Comparison of Phospholipid-Based Particles for Sustained Release of Ciprofloxacin Following Pulmonary Administration to Bronchiectasis Patients. (PubMed, Pulm Ther) - "While the formulations are similar in many respects, they also present some interesting differences. This review explores the implications of these differences on the treatment of respiratory infections."

Clinical • Journal • Review

Inhaled Ciprofloxacin (ARD-3150) in Patients with Non-Cystic Fibrosis Bronchiectasis and Frequent Pulmonary Exacerbations: A Pooled Analysis from ORBIT-3 and ORBIT-4 (ATS 2019) - P3; "ARD-3150 showed concordant results in both Phase 3 trials, resulting in a clinically meaningful 44% risk reduction in PEs requiring the administration of antibiotics in this phenotypic population of patients with bronchiectasis and severe disease associated with chronic lung infection with P. aeruginosa."

Retrospective data