ALIS Improves Symptoms in Newly Diagnosed MAC Lung Disease, With Charles Daley, MD

Amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy improved respiratory symptoms and produced high rates of sputum culture conversion in patients with newly diagnosed Mycobacterium avium complex lung disease (MACLD), according to findings from the phase 3b ENCORE trial presented at the 2026 American Thoracic Society (ATS) International Conference in Orlando, Florida.1

In an on-site interview at ATS 2026, Charles Daley, MD, from the National Jewish Health, said the randomized, double-blind ENCORE study demonstrated both clinical and microbiologic benefit when ALIS was used earlier in the disease course rather than reserved for refractory disease.

MACLD remains the leading cause of nontuberculous mycobacterial lung disease and is associated with chronic respiratory symptoms, progressive lung damage, impaired quality of life, and 5-year mortality rates approaching 42%.1 ALIS is currently approved for refractory MACLD, based largely on the phase 3 CONVERT trial, but ENCORE evaluated whether earlier initiation in newly diagnosed disease could improve outcomes before patients progress to more advanced illness.2 Daley said the rationale stemmed directly from prior refractory MACLD data showing meaningful efficacy despite treatment in highly difficult-to-manage populations.

“We said, ‘Well, this is an active drug. Why are we waiting for people to fail to give it to them?’” Daley said. “Why don’t we give it to them at the beginning and see what kind of impact we would have?”

The phase 3b ENCORE study randomized adults with newly diagnosed noncavitary MACLD to receive either ALIS plus azithromycin and ethambutol or an empty liposome control plus azithromycin and ethambutol for 12 months.1Participants had symptomatic MACLD with impaired respiratory quality-of-life scores and at least 2 positive sputum cultures (before enrollment and at screening).

The study’s primary endpoint evaluated change in patient-reported respiratory symptom score using a validated instrument derived from the Quality of Life-Bronchiectasis Respiratory Domain (QOL-B RD).1 Daley said the findings demonstrated clinically meaningful improvement in how patients felt over the course of therapy.

Investigators also reported high rates of microbiologic response, including culture conversion rates that exceeded those historically observed in MACLD studies.1

“By 6 months, almost 88% of the participants [had] culture converted,” Daley said. “…that’s pretty dramatic.”

No unexpected safety findings emerged during the trial. Known adverse events associated with inhaled amikacin, including dysphonia and cough, occurred at rates similar to prior studies in refractory disease, although treatment discontinuation rates due to intolerance appeared lower in the newly diagnosed population. He suggested newly diagnosed patients may tolerate therapy better because they are less clinically advanced than refractory MACLD populations.1

If the ENCORE data ultimately support the incorporation of ALIS into earlier-line MACLD treatment strategies, Daley said pulmonologists and infectious disease specialists may need to recalibrate treatment discussions with newly diagnosed patients. He said they should keep the higher culture conversion rates in mind, which may result in a shorter duration of therapy.

Daley also emphasized the rigor of the ENCORE trial design, highlighting extensive sputum culture collection and high protocol adherence across study sites.

“This study was really well conducted,” he said. “Over the course of a year, we got 95% of the expected sputum cultures. That’s unbelievable.”

Editor’s note: Relevant disclosures for Daley include Insmed, E.R. Squibb & Sons, Merck Sharp & Dohme, and Electromed.

References

1. Daley C, Morimoto K, Thomson R, et al. (Poster Board # P566) Amikacin Liposome Inhalation Suspension for Newly Diagnosed Mycobacterium Avium Complex Lung Disease: Efficacy and Safety From a Phase 3b Study (ENCORE). Latebreaker presented at ATS 2026 in Orlando, Florida, on May 17, 2026.

2. Morimoto K, Nonaka M, Yamazaki Y, et al. Amikacin liposome inhalation suspension for Mycobacterium avium complex pulmonary disease: A subgroup analysis of Japanese patients in the randomized, phase 3, CONVERT study. Respir Investig. 2024;62(2):284-290. doi:10.1016/j.resinv.2023.12.012