Inhaled Amikacin Raises Culture Conversion in New MAC Lung Disease

Amikacin liposome inhalation suspension (ALIS; Arikayce; Insmed) added to background azithromycin (Zithromax; Pfizer) and ethambutol (Myambutol; Lupin) produced significantly higher culture conversion rates in patients with a new occurrence of Mycobacterium avium complex lung disease (MACLD), with few cases of treatment-emergent resistance.¹ The findings come from a late-breaking analysis of the phase 3b ENCORE trial (NCT04677569), presented by Kevin L. Winthrop, MD, MPH, of Oregon Health & Science University, at IDWeek 2026, along with a separate real-world claims analysis.^1,2 The claims analysis found that starting multidrug therapy (MDT) was associated with fewer hospitalizations and respiratory exacerbations than watchful waiting.²

The first abstract focuses on culture conversion and resistance and includes no safety data.¹ The trial's primary end point, change in patient-reported respiratory symptoms at month 13,³ was reported earlier this year. The ENCORE data were presented at the American Thoracic Society (ATS) conference in May.⁴ In that presentation, no new safety signals were reported, but bronchospasm occurred in 23.0% of patients in the ALIS arm vs 11.8% in the comparator arm, and hypersensitivity pneumonitis in 2.3% vs 0.

ALIS With MDT Improves Culture Conversion

ENCORE randomized 425 patients with a new occurrence of MACLD, initial or subsequent, who had not started antibiotics for their current infection.¹ Patients received once-daily azithromycin 250 mg and ethambutol 15 mg/kg with either ALIS 590 mg (n = 213) or an empty liposome control (n = 212) for 12 months.

Culture conversion was higher in the ALIS arm at all 3 time points reported. Conversion at months 12 and 13 required 2 consecutive negative cultures (months 11 and 12 and months 12 and 13, respectively). Rates at month 12, the end of treatment, were 84.7% with ALIS vs 61.3% with the comparator. One month off treatment, rates were 82.4% vs 55.6%. Durable culture conversion at month 15, defined as negative MAC cultures at months 11, 12, 13, and 15, was reached by 76.2% vs 47.6%. All comparisons had P < .0001.

Study and treatment completion rates exceeded 90% and 80%, respectively, and treatment compliance exceeded 90%.

Resistance Was Uncommon

Because antibiotic resistance in MACLD is linked to low culture conversion rates, limited treatment options, and increased mortality, investigators examined susceptibility before, during, and after treatment. Resistance was defined as an amikacin minimal inhibitory concentration (MIC) of 128 µg/mL or higher and/or a clarithromycin MIC of 32 µg/mL or higher. Clarithromycin was the agent used to test macrolide susceptibility, although patients took azithromycin.

Of 761 patients screened, 5 were ineligible because of baseline resistance to amikacin (n = 2) or clarithromycin (n = 3). Among the 93 patients in the ALIS arm with at least one MAC-positive culture, 2 (2.2%) developed amikacin-resistant isolates, compared with none of the 165 in the comparator arm. Clarithromycin resistance emerged in 1 of 93 patients in the ALIS arm (1.1%) and 3 of 165 in the comparator arm (1.8%). The abstract reports no statistical comparison of resistance between arms.

The authors concluded that the combination of higher culture conversion and rare resistance supports adding ALIS to MDT.

“In ENCORE, treatment-emergent amikacin and macrolide resistance were uncommon,” they wrote. “Combined with higher culture conversion rates, these findings support ALIS with MDT as an effective MACLD treatment option with a low observed risk of resistance.”

Real-World Data Link MDT Initiation to Fewer Hospitalizations

The second abstract used a closed claims database to examine what drives MDT initiation and how treatment compares with watchful waiting.² The analysis included 5370 adults with 2 or more nontuberculous mycobacteria pulmonary infection claims between January 1, 2020, and November 30, 2025. Of these, 1596 started guideline-based MDT, and 3774 did not.

Among those who started MDT, 918 (57.5%) received a 3-drug regimen of a macrolide, ethambutol, and rifampin (Rifadin; Sanofi-Aventis), and 607 (38.0%) received a 2-drug regimen.

Patients who started MDT were slightly younger (mean age, 60.1 vs 64.3 years) and more likely to be male (40.4% vs 30.4%). They also had higher baseline Charlson Comorbidity Index scores. Factors associated with MDT initiation included immunosuppressive therapy use (odds ratio [OR], 1.95; 95% CI, 1.69-2.25), bronchiectasis (OR, 1.76; 95% CI, 1.54-2.01), idiopathic interstitial lung disease (OR, 1.73; 95% CI, 1.34-2.24), smoking (OR, 1.47; 95% CI, 1.25-1.72), male sex (OR, 1.46; 95% CI, 1.28-1.67), and chronic obstructive pulmonary disease (OR, 1.33; 95% CI, 1.16-1.53).

After 1:2 propensity score matching, adjusted analyses favored MDT for several outcomes. Relative risks were 0.71 (95% CI, 0.59-0.85) for all-cause hospitalization, 0.67 (95% CI, 0.54-0.84) for respiratory-related hospitalization, and 0.83 (95% CI, 0.71-0.97) for respiratory exacerbation. Differences in emergency department visits did not reach statistical significance.

Limitations

Claims data cannot identify the infecting species, so the authors excluded patients treated for M abscessus to reduce misclassification. Claims also lack data on symptom severity, culture conversion, and cavitary disease. Closed claims databases mostly capture commercially insured patients and do not represent Medicare fee-for-service, Medicaid, and uninsured populations.

For ENCORE, investigators acknowledged at ATS that participants had noncavitary disease, did not have cystic fibrosis, and were nonsmokers, which may limit generalizability.⁴

Regulatory Status and Disclosures

ALIS is approved only for refractory MACLD.² Insmed's supplemental new drug application, seeking full approval for MACLD as part of a combination regimen, is under FDA priority review, with a target action date of January 28, 2027.⁵ Insmed sponsors ENCORE and funded the poster.² Six of the 15 ENCORE authors list Insmed affiliations.¹ Two of the 4 poster authors are Insmed employees and shareholders, and a third is a paid Insmed consultant. Winthrop, the presenting author of both, discloses serving as a consultant and principal investigator in multiple trials sponsored by Insmed and other companies.²

References

1. Winthrop KL, Flume PA, O'Donnell AE, et al. Amikacin and macrolide resistance in patients with newly diagnosed Mycobacterium avium complex lung disease: results from ENCORE. Late-breaking abstract presented at: IDWeek 2026; October 22, 2026; Washington, DC.
2. Winthrop KL, Waweru C, Ward T, Silva D. Real-world evidence of treatment drivers and outcomes in patients diagnosed with Mycobacterium avium complex lung disease (MACLD). Poster P-475 presented at: IDWeek 2026; October 21-24, 2026; Washington, DC.
3. 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 3b study (ENCORE). Am J Respir Crit Care Med. 2026;Suppl 2:A71-12. doi:10.1093/ajrccm/aamag286.341
4. McCormick B. ALIS plus multidrug therapy improves symptoms, culture conversion in newly diagnosed MAC lung disease. AJMC. Published May 18, 2026. Accessed October 21, 2026. https://www.ajmc.com/view/alis-plus-multi-drug-therapy-improves-symptoms-culture-conversion-in-newly-diagnosed-mac-lung-disease
5. Johnson V. FDA grants priority review for Insmed's ARIKAYCE sNDA for MAC lung disease. HCPLive. Published September 21, 2026. Accessed October 21, 2026. https://www.hcplive.com/view/fda-grants-priority-review-insmed-arikayce-snda-mac-lung-disease