ENCORE ALIS Data Could Reshape First-Line MACLD: Jakko van Ingen, MD, PhD

The phase 3b ENCORE trial assessing amikacin liposome inhalation suspension (ALIS) added to multidrug therapy in antibiotic-naive adults with newly diagnosed Mycobacterium avium complex lung disease (MACLD) met its primary end point, with significantly greater improvement in respiratory symptoms in the ALIS arm versus comparator at month 13 (P = .0299), and showed significantly higher rates of culture conversion at months 6, 12, and 13, along with durable culture conversion at month 15 (P <.0001).

ENCORE's decision to use a patient-reported respiratory symptom score, rather than a purely microbiologic measure, as its primary endpoint reflects an FDA requirement, but also a deliberate shift in what the trial was designed to prove, according to Jakko van Ingen, MD, PhD, professor of diagnostics and antimicrobial therapy of mycobacterial infections at Radboud University Medical Center. Van Ingen discussed the trial in an interview with HCPLive about data presented as a late-breaking abstract at the 2026 European Respiratory Society (ERS) Congress, held September 5 to 9 in Barcelona, Spain.¹

Van Ingen said that as a microbiologist, his instinct is to focus on whether the causative bacteria are eliminated, but that outcome is ultimately a means to an end.

“You do that because you want the person suffering from this terrible disease to improve, to feel better, to be able to live a happy life,” he said, noting that ENCORE tracked whether patients' symptoms improved not only during treatment but through the first 3 months after treatment ended, rather than relying solely on culture status as a proxy for how patients actually felt.

On where ALIS might fit going forward, van Ingen said the trial's design leaves an important caveat: the comparator arm in ENCORE was itself a deviation from current treatment guidelines, meaning the study did not directly compare ALIS against the guideline-recommended first-line regimen. He was candid, however, about how thin the evidence base for that existing first-line regimen actually is, describing it as supported mainly by case series and a single trial still nearing completion, and said there is in fact some evidence that runs counter to that current standard.

“As a microbiologist, I have to say there's actually evidence that speaks against the regimen that we currently consider to be the first-line treatment regimen. So, in that light, I do see that the the ENCORE trial supports the position of ALIS as part of a first-line multi-drug treatment for earlier stages of non-cavitary MMACLD,” Van Ingen said.

Importantly, the United States Food and Drug Administration (FDA) today granted Priority Review to Insmed's supplemental new drug application (sNDA) for ALIS for full approval for newly diagnosed and recurrently infected MACLD, with a PDUFA target action date of January 28, 2027, based off findings from ENCORE.³

van Ingen’s disclosures include Paratek, Insmed, MannKind, and AN2 Therapeutics.

References

1. van Ingen J, Van Braeckel E, Feng J, et al. Microbiologic outcomes and recurrence in patients with newly diagnosed Mycobacterium avium complex lung disease (MACLD) in the phase 3b ENCORE trial. Late-breaking abstract presented at: European Respiratory Society (ERS) Congress 2026; September 5-9, 2026; Barcelona, Spain.

2. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020;56(1):2000535. doi:10.1183/13993003.00535-2020

3. Johnson V. FDA Grants Priority Review for Insmed's ARIKAYCE sNDA for MAC Lung Disease. September 21, 2026. Article. HCPLive. https://www.hcplive.com/view/fda-grants-priority-review-insmed-arikayce-snda-mac-lung-disease