ENCORE: Early ALIS Cuts MACLD Recurrence, With Jakko Van Ingen, MD, PhD

More than 40% of patients with Mycobacterium avium complex lung disease (MACLD) fail to achieve microbiologic success on standard multidrug therapy (MDT) alone, and recurrence after apparent treatment success is common, according to Jakko van Ingen, MD, PhD, professor of diagnostics and antimicrobial therapy of mycobacterial infections at Radboud University Medical Center. Van Ingen discussed new data from the phase 3b ENCORE trial evaluating Insmed’s add-on amikacin liposome inhalation suspension (ALIS; ARIKAYCE), presented as a late-breaking abstract at the 2026 European Respiratory Society (ERS) Congress, held September 5 to 9 in Barcelona, Spain, in an interview with HCPLive.

What did ENCORE assess?

ENCORE enrolled antibiotic-naive adults with newly diagnosed MACLD, randomizing them to once-daily MDT (azithromycin 250 mg and ethambutol 15 mg/kg) plus either ALIS 590 mg or an empty-liposome comparator for 12 months.1

The trial met its primary endpoint, 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).1 Van Ingen said culture conversion should not be treated as a binary, one-time event. “Even if you respond to treatment initially, there is a chance that you will get either reinfected or your original infection will creep up again despite having been on antibiotic treatment,” he said, adding that durability of conversion, meaning patients stayed culture-negative through treatment and for 3 months after stopping, is what makes the result clinically meaningful.

Using whole genome sequencing, investigators distinguished relapse (recurrence of the original infecting strain) from reinfection (a genetically distinct organism) among patients who had a positive culture after initially converting.1 Van Ingen called this distinction one of the most important findings of the trial, noting that very few studies, and essentially none in the context of a controlled clinical trial, have examined this phenomenon before.

What do the findings mean?

“We've learned that maybe these reinfections are something we should accept, or something that future drug regimens may have to address, but at least the number of relapses we can reduce,” he said, adding that further refinements to treatment regimens could reduce relapse rates even further over time. He said the findings confirm a small number of previously reported, smaller-scale observations, lending additional weight to the result as a genuine and clinically meaningful improvement rather than a chance finding.

Van Ingen said this distinction matters because patients who fail treatment once are substantially harder to cure going forward. “If you can prevent people from getting to that stage of what we sadly call refractory disease, I think that's a major plus,” he said, noting that culture conversion rates in ENCORE's ALIS arm exceeded what has been reported in meta-analyses of prior published case series.

He said the trial cannot yet answer questions about very long-term outcomes given the ongoing risk of reinfection, but said the short-term data support treating newly diagnosed, antibiotic-naive patients more aggressively before they progress to refractory disease, which remains difficult to treat with existing regimens.

Notably, 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

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. ClinicalTrials.gov. A study to assess the efficacy and safety of ALIS plus multi-drug regimen versus multi-drug regimen alone in adult subjects with newly diagnosed MAC lung disease (ENCORE). Identifier: NCT04677569.

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