ALIS Plus Multidrug Therapy Improves Symptoms, Culture Conversion in Newly Diagnosed MAC Lung Disease

Adding amikacin liposome inhalation suspension, or ALIS (Arikayce; Insmed), to multidrug therapy (MDT) significantly improved both respiratory symptoms and culture conversion outcomes in adults with newly diagnosed Mycobacterium avium complex lung disease (MACLD), according to late-breaking phase 3 ENCORE trial findings presented at the American Thoracic Society (ATS) 2026 International Conference.¹

Addressing High Disease Burden in MACLD

MACLD is the leading cause of nontuberculous mycobacterial lung disease. It is a chronic condition associated with a high symptom burden, impaired quality of life, and a 5-year all-cause mortality rate of up to 42%. Because of this, researchers emphasized the need for effective front-line treatment options to prevent further disease progression. In 2018, the FDA approved ALIS for the treatment of MACLD as part of MDT in a limited population of adult patients who do not achieve culture conversion after 6 months of MDT.²

The ENCORE trial (NCT04677569) evaluated the efficacy and safety of ALIS plus MDT (azithromycin [AZI] and ethambutol [ETH]) vs placebo (empty liposome control) with MDT (AZI and ETH) in adults with newly diagnosed MACLD who had not previously received antibiotics.³ Described as the largest randomized, double-blind, multinational, superiority clinical trial to date in this population, findings were presented on May 17 at the 2026 ATS International Conference in Orlando, Florida.¹

The primary end point was change from baseline to month 13 in the Respiratory Symptom Score (RSS), a recently validated 8-item measure derived from the Quality of Life Questionnaire-Bronchiectasis Respiratory Domain (QOL-B RD). Like the QOL-B RD, the RSS is standardized on a scale of 0 to 100, with higher scores indicating fewer symptoms.

The key secondary end point was durable culture conversion at month 15, defined as no MAC growth on solid and liquid media at months 11, 12, 13, and 15. Additional secondary end points included culture conversion by months 6, 12, and 13, defined as no MAC growth on solid and liquid media in all sputum cultures at 2 consecutive visits.

Eligible patients were adults with a current diagnosis of MACLD who had a positive culture for MAC within 6 months of screening and again at screening. Participants also had an average QOL-B RD domain score of 85 or lower both at screening and on the day of enrollment before randomization. In addition, the patients had underlying lung disease managed according to the best local standard of care and were receiving stable maintenance therapy for at least 4 weeks before randomization.

ALIS Plus MDT Shows Significant Symptom and Culture Conversion Benefits

The trial enrolled 425 patients, with completion rates exceeding 90% in both arms. Baseline characteristics and demographics were generally well-balanced between the arms and representative of patients with newly diagnosed MACLD.

ALIS produced a statistically significant greater improvement in RSS from baseline to month 13 compared with the control arm (least squares [LS] mean change, 17.77 vs 14.66 points; treatment difference, 3.11 points; P = .0299). The treatment difference widened further at month 15 to 4.80 points (nominal P = .0015). Additionally, clinically meaningful improvement, defined as a within-patient change of at least 16.67 points, was achieved by 53.4% of patients in the ALIS arm vs 45.4% in the comparator arm.

The researchers found all culture conversion secondary end points to be statistically significantly higher in the ALIS arm. In addition, earlier time to culture conversion was associated with consistently higher conversion rates over time.

No new safety signals were observed, and most treatment-emergent adverse events (TEAEs) were mild or moderate in severity. However, one death occurred in each study arm, but neither was considered treatment-related. TEAEs of special interest were generally comparable between treatment groups, although bronchospasm (ALIS arm, n = 49 [23.0%]; comparator arm, n = 25 [11.8%]) and hypersensitivity pneumonitis (ALIS arm, n = 5 [2.3%]; comparator arm, n = 0) were more common in the ALIS arm.

Investigators Acknowledge Study Limitations While Supporting ALIS Benefits

The researchers acknowledged a limitation of the study: all participants met a specific QOL-B RD score threshold for enrollment, had noncavitary disease, did not have cystic fibrosis, and were nonsmokers, which may limit the generalizability of their findings. Still, they expressed confidence in the results.

“ENCORE demonstrated that a fixed 12-month duration of treatment resulted in a durable benefit, a finding that may represent a potentially important shift in the current clinical practice of patients with MACLD,” the authors wrote.

References

1. Daley CL, Morimoto K, Thomson R, et al. Amikacin liposome inhalation suspension for newly diagnosed Mycobacterium avium complex lung disease: efficacy and safety from a phase 3 study (ENCORE). Presented at: American Thoracic Society 2026 International Conference. May 17-20, 2026; Orlando, Florida. Poster P566.
2. Insmed announces FDA approval of ARIKAYCE (amikacin liposome inhalation suspension), the first and only therapy specifically indicated for the treatment of Mycobacterium avium complex (MAC) lung disease in adult patients with limited or no alternative treatment options. News release. Insmed. September 28, 2018. Accessed May 18, 2026. https://investor.insmed.com/2018-09-28-Insmed-Announces-FDA-Approval-of-ARIKAYCE-R-amikacin-liposome-inhalation-suspension-the-First-and-Only-Therapy-Specifically-Indicated-for-the-Treatment-of-Mycobacterium-Avium-Complex-MAC-Lung-Disease-in-Adult-Patients-with-Limited-or-No-Alterna
3. Study to evaluate ALIS (amikacin liposome inhalation suspension) in participants with nontuberculous myobacterial lung infection caused by myobacterium avium complex (ENCORE). ClinicalTrials.gov. Last updated February 3, 2026. Accessed May 18, 2026. https://clinicaltrials.gov/study/NCT04677569