ANALYSIS OF LONG-TERM LIPOSOMAL AMIKACIN FOR INHALATION IN PATIENTS WITH CYSTIC FIBROSIS AND CHRONIC INFECTION FROM PSEUDOMONAS AERUGINOSA

INTRODUCTION • Liposomal amikacin for inhalation (LAI) is a novel formulation of amikacin currently in development for the treatment of patients with lung infections caused by Pseudomonas aeruginosa and nontuberculous mycobacteria (NTM).1,2 • LAI is composed of charge-neutral, highly biocompatible liposomes (~0.3 μm) that encapsulate amikacin and penetrate the biofilm to achieve a high drug concentration at the site of infection (Figure 1).1,2 • Key features of LAI include1: – High lung concentration (Cmax) and area under the curve (AUC), as well as longer half-life (t1⁄2), which result in improved AUC: minimum inhibitory concentration (MIC) ratio that enables once-daily dosing – Potent P aeruginosa killing, including resistant isolates – Additional release of amikacin from LAI when virulence factors are secreted by P aeruginosa – Potent in vitro and in vivo NTM killing that is superior to amikacin solution • In preclinical studies, the lung level of LAI administered once daily (QD) was approximately 5 times greater than the level of an equivalent amount of tobramycin inhalation solution (TIS), USP, given twice daily (BID).1