P-760. Amikacin-Liposome Inhalation Suspension (ALIS) for Refractory MACLD: Simultaneous Analysis of Efficacy and Safety
Authors: Dorgan Daniel , Waweru Catherine , Cocks Kim , Lawrance Rachael , Hunger Matthias , Pahwa Ankit , Yuen Dayton , Ciesielska Monika , Markson Leona 
Published: January 2025

Abstract

Background
Patients with refractory Mycobacterium avium complex lung disease (rMACLD) represent a difficult to treat population, who have not achieved culture conversion (CC) despite prolonged treatment with multidrug antibacterial regimen (MDR). In the CONVERT trial, amikacin liposome inhalation suspension (ALIS) + MDR resulted in higher CC rates than MDR alone during the first 6 months of treatment (29% vs 9%) in patients that had positive cultures on MDR for at least 6 months. Adverse events (AEs) following treatment initiation were reported in 98% and 91% of patients in the ALIS+MDR and MDR alone arms, respectively, and were mostly of mild to moderate severity. A simultaneous assessment of efficacy and safety of treatment could be informative during clinical decision making. We adapted well-established Time Without Symptoms and Toxicity “TWiST” methodology to compare ALIS + MDR vs MDR alone, using a singular metric of time spent with CC and without severe AEs.
Figure 1. Partitioned survival curves for ALIS+MDR

Methods
The time from randomization to month 6 in CONVERT was partitioned into 4 health states:
• Time spent with severe (≥ grade 3) AEs prior to CC (AE1)
• Time spent without CC, without severe AEs (No CC)
• Time spent with severe AEs after CC (AE2)
• Time spent with CC and without severe AEs (referred to as ideal health state)
Kaplan-Meier methods were used to estimate health state durations (days); p-values were estimated using bootstrapping with 10,000 replications.Figure 2.Partitioned survival curves for MDR alone

Results
Mean follow-up was 180.2 and 179.7 days in the ALIS+MDR and MDR alone treatment arms, respectively. Patients in the ALIS+MDR arm spent a mean of 9.4 days with severe AEs prior to CC vs 1.4 with MDR alone (p &lt; 0.001) (Figure 1, Figure 2). There was no statistically significant difference in the mean time spent with severe AEs following CC between treatment arms (ALIS+MDR vs MDR: 1.8 vs 0.6 days; p = 0.2). The mean number of days spent in the ideal health state was statistically significantly higher with ALIS+MDR vs MDR alone (38.8 vs 14.5 days; p &lt; 0.001).

Conclusion
Although there were more AEs on ALIS+MDR than MDR alone in the CONVERT trial, this simultaneous assessment of efficacy and safety demonstrates that ALIS+MDR was more likely to result in more time in the ideal health state of CC without severe AEs than MDR alone. These data may inform clinical decision-making in the treatment of rMACLD.

Disclosures
Daniel Dorgan, MD, Insmed Incorporated: Advisor/Consultant Catherine Waweru, PhD, Insmed Incorporated: Employee|Insmed Incorporated: Stocks/Bonds (Public Company) Kim Cocks, PhD, Adelphi Values: Employee Rachael Lawrance, BSc, Adelphi Values: Employee Matthias Hunger, MSc, ICON Clinical Research: Employee Ankit Pahwa, MS, ICON Clinical Research: Employee Dayton Yuen, PharmD, Insmed Incorporated: Employee|Insmed Incorporated: Stocks/Bonds (Public Company) Monika Ciesielska, MA, Insmed Incorporated: Employee|Insmed Incorporated: Stocks/Bonds (Public Company) Leona Markson, ScD, Insmed Incorporated: Employee|Insmed Incorporated: Stocks/Bonds (Public Company)