A71-12 Amikacin Liposome Inhalation Suspension for Newly Diagnosed Mycobacterium Avium Complex Lung Disease: Efficacy and Safety From a Phase 3b Study (ENCORE)

Rationale

Mycobacterium avium complex lung disease (MACLD), the leading cause of nontuberculous mycobacterial lung disease, is a chronic infection with high symptom burden, lung function decline, impaired quality of life, and a 5-year all-cause mortality rate up to 42%. Effective first-line treatment options are critical to prevent further deterioration. ENCORE (NCT04677569) is a large, phase 3b, randomized, double-blind, multicenter, placebo-controlled trial designed to evaluate the efficacy and safety of amikacin liposome inhalation suspension (ALIS) plus azithromycin and ethambutol with an active comparator (empty liposome control [ELC] plus azithromycin and ethambutol) in adults with newly diagnosed MACLD (Figure).

Methods

Adults with a current diagnosis of noncavitary MACLD, documented respiratory symptoms attributable to current MAC lung infection (average Quality of Life-Bronchiectasis Respiratory Domain [QOL-B RD] score ≤85), and two positive sputum cultures (1 prior to and 1 at screening) were enrolled. Patients who had received antimycobacterial antibiotic treatment for their current MAC lung infection were excluded. Eligible patients were randomized 1:1 to receive ALIS 590mg plus azithromycin 250mg and ethambutol 15mg/kg, or ELC plus azithromycin 250mg and ethambutol 15mg/kg (all once daily) for 12 months. Randomization was stratified by region and history of MAC lung infection (initial or subsequent). After stopping study drugs at month 12, patients were followed for 3 months. Efficacy endpoints will be analyzed hierarchically. The primary endpoint is change from baseline to month 13 in patient-reported respiratory symptom score (RSS; derived from QOL-B RD). Secondary efficacy endpoints in the analysis hierarchy are sputum culture conversion by month 13, durability of culture conversion at month 15, culture conversion by month 12, culture conversion by month 6, and change from baseline to month 13 in patient-reported fatigue symptoms. Treatment-emergent safety data will be summarized from the first dose to 28 days after discontinuation of ALIS or ELC.

Results

Primary, principal secondary, and safety endpoints will be presented.

Conclusions

ALIS safety and efficacy have been established in patients with refractory MACLD in previous clinical trials. ENCORE was designed to evaluate the clinical benefit of ALIS added to an antibiotic regimen in patients with MACLD using a newly validated patient-reported endpoint, as well as explore the utility of ALIS for a fixed treatment duration among patients with newly diagnosed MACLD.

This abstract is funded by: Insmed Incorporated