Amikacin Liposome Inhalation Suspension for Mycobacterium avium Complex Lung Disease A 12-Month Open-Label Extension Clinical Trial

Rationale: Patients with refractory Mycobacterium avium complex (MAC) lung disease have limited treatment options. In the CONVERT study, amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) increased culture conversion rates versus GBT alone by Month 6. Limited data are available regarding.6-month treatment in a refractory population. Objectives: Evaluate 12-month safety, tolerability, and efficacy of ALIS1GBT. Methods: Adults with refractory MAC lung disease not achieving culture conversion by CONVERT Month 6 could enroll in this openlabel extension (INS-312) to receive 590 mg once-daily ALIS1GBT for 12 months. Two cohorts enrolled: the "ALIS-naive" cohort included patients randomized to GBT alone in CONVERT, and the "prior-ALIS" cohort included those randomized to ALIS1GBT in CONVERT. Safety and tolerability of ALIS over 12 months (primary endpoint) and culture conversion by Months 6 and 12 were assessed. Results: In the ALIS-naive cohort, 83.3% of patients (n = 75/90) experienced respiratory treatment-emergent adverse events (TEAEs), and 35.6% (n= 32) had serious TEAEs; 26.7% (n = 24) achieved culture conversion by Month 6 and 33.3% (n= 30) by Month 12. In the prior-ALIS cohort, 46.6% of patients (n= 34/73) experienced respiratory TEAEs, and 27.4% (n= 20) had seriousTEAEs; 9.6% (n = 7) achieved culture conversion by Month 6 (<14 mo ALIS exposure) and 13.7% (n= 10) byMonth 12 (<20 mo ALIS exposure). Nephrotoxicity-related TEAEs and measured hearing decline were infrequent in both cohorts. Conclusions: In up to 20 months of ALIS use, respiratory TEAEs were common, nephrotoxicity and hearing decline were infrequent, and culture conversion continued beyond 6 months of therapy.