Phase 3b ENCORE data show ARIKAYCE improves symptoms and culture conversion in newly diagnosed MAC lung disease, supporting earlier use. Findings suggest potential to shift treatment earlier and improve outcomes in this difficult-to-treat infection.
New data from the Phase 3b ENCORE study indicate that ARIKAYCE (amikacin liposome inhalation suspension) may offer meaningful clinical benefit earlier in the treatment course for patients with Mycobacterium avium complex (MAC) lung disease, a serious and often progressive infection with limited treatment options.
"MAC lung disease is an especially difficult-to-treat infection that becomes increasingly challenging as it progresses, underscoring the importance of effective intervention,” Martina Flammer, MD, MBA, chief medical officer of Insmed told Infection Control Today® (ICT®).
The randomized, double-blind, placebo-controlled trial evaluated ARIKAYCE in combination with standard multidrug therapy consisting of azithromycin and ethambutol in patients newly diagnosed with MAC lung infection who had not yet received antibiotics. A total of 425 patients were enrolled across 177 global sites, reflecting a broad and diverse study population.
The study met its primary endpoint, demonstrating a statistically significant improvement in respiratory symptoms at 13 months compared with standard therapy alone. Patients receiving ARIKAYCE showed a greater change in Respiratory Symptom Score (RSS), with a treatment difference of 3.11 points, indicating clinically meaningful improvement.
Flammer told ICT, “The ENCORE results clearly show that earlier use of ARIKAYCE plus multidrug therapy in diagnosed patients with a new occurrence of MAC lung infection who had not received antibiotics is associated with earlier and improved rates of culture conversation, including durability of response 1 and 3 months after the treatment was completed, alongside statistically significant improvements in respiratory symptoms as measured by the RSS.”
In addition to symptom improvement, ARIKAYCE demonstrated strong microbiologic outcomes. Culture conversion rates, a key marker of treatment success, were significantly higher in the ARIKAYCE group across all measured time points. By month 6, 87.8% of patients receiving ARIKAYCE achieved culture conversion, compared with 57.0% in the control group. These benefits persisted through month 13 and remained durable at month 15, with 76.2% of ARIKAYCE-treated patients maintaining culture conversion versus 47.6% of those receiving standard therapy alone.
“These results are an exciting win for patients living with MAC lung disease and a powerful validation of ARIKAYCE’s ability to deliver real clinical benefit,” said Flammer. She added that the findings support the potential for earlier use of the therapy in the course of the disease.
David Griffith, MD, professor of medicine at National Jewish Health and a member of the ENCORE steering committee, emphasized the broader clinical implications. “These groundbreaking results show that patients may have significant clinical benefit from including ARIKAYCE earlier in their treatment journey,”
The safety profile observed in ENCORE was consistent with previous studies, with no new safety signals identified. Common adverse events included dysphonia, cough, fatigue, dyspnea, and nausea, which are expected with inhaled therapies. While some respiratory-related adverse events, such as bronchospasm and hypersensitivity pneumonitis, occurred more frequently in the ARIKAYCE group, overall rates of serious adverse events were comparable between treatment arms.
MAC lung disease remains a growing public health concern, particularly among patients with underlying lung conditions or compromised immune systems. Symptoms such as chronic cough, fatigue, and shortness of breath can significantly impact quality of life, and in severe cases, the disease can lead to permanent lung damage or death.
Currently, ARIKAYCE is approved in the US for patients with refractory MAC lung disease who have not responded to standard therapy. The ENCORE findings build on this foundation, suggesting that earlier intervention may improve outcomes and reduce disease progression. Insmed plans to file a supplemental new drug application with the US Food and Drug Administration in the second half of 2026 to support expanded use of ARIKAYCE in newly diagnosed patients.
“Based on this large, randomized, controlled trial, we believe ARIKAYCE in combination with azithromycin and ethambutol has the potential to redefine front-line treatment of MAC lung disease,” Flammer told ICT. “We look forward to exploring the expansion of the ARIKAYCE indication in the U.S. and Japan, with the ultimate goal of improving outcomes for an even greater number of patients fighting this difficult disease."
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