ENCORE Trial Explores Earlier Amikacin Therapy for MAC

In "ENCORE Trial Explores Earlier Amikacin Therapy for MAC," the discussion turns to the ENCORE trial and its case for treating MAC earlier.

Dr. Losier reviews the ENCORE study, which tests amikacin liposome inhalation suspension, a therapy she shorthands as ALIS. The trial challenges the traditional timing of inhaled amikacin therapy, which has generally been reserved for refractory MAC after at least six months without culture conversion. By that point, she notes, disease may have already progressed and become harder to treat. ENCORE instead introduced the inhaled therapy at initial treatment, testing whether earlier use could improve both microbiologic outcomes and patient-reported respiratory symptoms.

The trial was a global, randomized, double-blind, placebo-controlled Phase 3B study conducted at 177 sites across 22 countries. It enrolled treatment-naive adults with newly diagnosed, non-cavitary MAC lung disease who had respiratory symptoms and at least two positive cultures. Patients were randomized to once-daily inhaled amikacin liposome plus azithromycin and ethambutol, or to an empty liposomal comparator plus the same two drugs, for 12 months. Endpoints included change in quality-of-life bronchiectasis respiratory domain scores and durable culture conversion.

At six months, culture conversion reached approximately 88% in the amikacin arm versus 57% in the comparator, and the advantage persisted, with differences of 23% to 31% at months 12, 13, and 15. The study also met its primary patient-reported outcome endpoint, showing clinically meaningful improvement in respiratory symptoms. Adverse events were similar between arms, roughly 14% versus 11%, with one death in each group, neither treatment-related.

Dr. Losier's takeaway is that ENCORE challenges the paradigm of waiting for MAC to become refractory before starting inhaled amikacin. While not every newly diagnosed patient needs it, she says the data support considering earlier use in selected, symptomatic patients, potentially even shortening overall treatment duration.

The next episode, "All-Oral Bedaquiline Regimen for Refractory MAC Lung Disease," the discussion moves to an all-oral option for patients whose MAC has become refractory to standard therapy.