Phase 3b ENCORE results show ARIKAYCE plus multidrug therapy improved respiratory symptoms and culture conversion in newly diagnosed MAC lung infection.
Written By: Karthik Teja Macharla, PharmD
Reviewed By: Pharmacally Editorial Team
Insmed has reported positive topline results from the Phase 3b ENCORE trial (NCT04677569) evaluating ARIKAYCE® (amikacin liposome inhalation suspension) added to standard multidrug therapy in patients with a newly diagnosed Mycobacterium avium complex (MAC) lung infection who had not previously received antibiotic treatment. The randomized, double-blind, placebo-controlled study enrolled 425 patients across 177 global sites, comparing once-daily ARIKAYCE plus azithromycin and ethambutol against placebo plus the same multidrug regimen.
Martina Flammer, M.D., MBA Chief Medical Officer, Insmed stated that the findings reinforce ARIKAYCE’s clinical value in MAC lung disease and support exploring its use earlier in treatment, with plans to pursue potential label expansion in the U.S. and Japan.
The trial met its primary endpoint, demonstrating a statistically significant improvement in respiratory symptoms at Month 13, with ARIKAYCE showing a greater improvement from baseline compared with the control arm (17.77 vs 14.66 points; p=0.0299).
Across key microbiologic secondary endpoints, ARIKAYCE showed substantially higher culture conversion rates versus the comparator regimen, including 87.8% vs 57.0% by Month 6, with consistent advantages maintained through Months 12 and 13 and durable culture conversion at Month 15 (76.2% vs 47.6%) (all p<0.0001). Improvement in fatigue measured by PROMIS Fatigue T-score was not statistically significant.
The safety profile was consistent with the known profile of ARIKAYCE, with no new safety signals observed. Overall rates of treatment-emergent adverse events were similar between groups, though respiratory-related reactions such as dysphonia, cough, and dyspnea were more frequent with ARIKAYCE. Certain events of interest, including bronchospasm and hypersensitivity pneumonitis, occurred more often in the ARIKAYCE arm, while other monitored toxicities such as ototoxicity, nephrotoxicity, and pulmonary exacerbations occurred at broadly comparable rates.
David Griffith, M.D. ENCORE Steering Committee Member, National Jewish Health
said the ENCORE results suggest that introducing ARIKAYCE earlier in multidrug therapy may provide meaningful clinical benefits for patients with MAC lung disease, as reflected by improvements in respiratory symptoms and durable culture conversion.
Completion of ENCORE fulfills a U.S. FDA post-marketing requirement for ARIKAYCE. Insmed plans to submit a supplemental NDA in the second half of 2026 seeking label expansion for use earlier in MAC lung disease and to support conversion of the drug’s current accelerated approval to traditional approval in the United States. The company also intends to submit the data to Japan’s PMDA for potential indication expansion.
ARIKAYCE is a once-daily inhaled liposomal formulation of amikacin designed to deliver the antibiotic directly to the lungs using Insmed’s PULMOVANCE™ liposomal technology, enabling uptake by lung macrophages at the infection site while limiting systemic exposure. MAC lung disease is a serious infection caused by non-tuberculous mycobacteria that can progressively damage the lungs and remains an area of significant unmet need.
ARIKAYCE is administered once daily via the Lamira® Nebulizer System, a portable inhalation device designed to aerosolize the liposomal amikacin formulation for delivery directly to the lungs.
For complete safety details, including warnings and precautions, refer to the U.S. Prescribing Information (USPI) for ARIKAYCE.
Reference
Insmed Announces Positive Topline Results from Phase 3b ENCORE Study of ARIKAYCE® (Amikacin Liposome Inhalation Suspension) in Patients with MAC Lung Disease, 23 March 2026, Insmed Announces Positive Topline Results from Phase 3b ENCORE Study of ARIKAYCE® (Amikacin Liposome Inhalation Suspension) in Patients with MAC Lung Disease – Mar 23, 2026
Study to Evaluate ALIS (Amikacin Liposome Inhalation Suspension) in Participants with Nontuberculous Mycobacterial Lung Infection Caused by Mycobacterium Avium Complex (ENCORE), ClinicalTrials.gov ID NCT04677569, https://clinicaltrials.gov/study/NCT04677569
About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.