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Insmed's Arikayce meets primary endpoint in Phase IIIb ENCORE study for MAC lung disease

Edited by Robert McTiernan··3 min read

Insmed (Nasdaq: INSM) reported that its Phase IIIb ENCORE study of Arikayce (amikacin liposome inhalation suspension) met its primary endpoint and all multiplicity-controlled secondary endpoints in patients with newly diagnosed Mycobacterium avium complex lung disease, generating data the company intends to use for a supplemental NDA filing with the US FDA in the second half of 2026. The results carry particular weight because Arikayce currently holds only accelerated approval in the United States, restricted to refractory MAC lung disease patients with limited treatment alternatives, and ENCORE was designed to fulfill the FDA's post-marketing requirement while also supporting potential label expansion to a broader, treatment-naive population.

ENCORE is a randomized, double-blind, placebo-controlled study conducted across 177 sites globally. It enrolled 425 patients with a new occurrence of MAC lung infection who had not previously received antibiotics, randomizing them 1:1 to once-daily Arikayce 590 mg plus multidrug therapy (azithromycin 250 mg and ethambutol 15 mg/kg) or placebo plus the same multidrug regimen for 12 months, followed by a three-month treatment-free observation period.

On the primary endpoint, change from baseline in Respiratory Symptom Score at Month 13, the Arikayce arm showed a 17.77-point improvement versus 14.66 points in the control arm, a treatment difference of 3.11 points (p=0.0299). The culture conversion results were more pronounced: 87.8% of Arikayce-treated patients achieved culture conversion by Month 6 compared with 57.0% on placebo (p<0.0001), a difference of approximately 31 percentage points. Durable culture conversion, assessed at Month 15 after three months off treatment, was 76.2% versus 47.6% (p<0.0001). The PROMIS Fatigue T-score, a multiplicity-controlled secondary endpoint, did not reach statistical significance (p=0.2900).

The safety profile was consistent with known risks of inhaled amikacin, and the company reported no new signals. Dysphonia was the most frequent treatment-emergent adverse event in the Arikayce arm at 58.7% versus 8.5% for placebo, followed by cough (32.9% vs. 14.6%). Among events of special interest, bronchospasm occurred in 23.0% of Arikayce patients versus 11.8% on placebo, and hypersensitivity pneumonitis was observed in 2.3% versus 0%. Discontinuation due to adverse events was higher in the Arikayce arm (14.6% vs. 8.5%), though study completion rates remained above 90% in both groups.

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Arikayce uses Insmed's Pulmovance liposomal technology to encapsulate amikacin, an aminoglycoside antibiotic that inhibits bacterial protein synthesis by binding the 30S ribosomal subunit. The liposomal formulation delivers the drug directly to the lungs via a nebulizer, where it is taken up by alveolar macrophages, the cells in which MAC organisms reside. This targeted delivery is intended to maximize local drug concentrations at the site of infection while reducing the systemic exposure that historically limited parenteral amikacin use due to ototoxicity and nephrotoxicity.

The treatment landscape for MAC lung disease remains constrained. Current guideline-recommended regimens typically combine a macrolide such as azithromycin with ethambutol and a rifamycin, but none of these agents carries a specific regulatory approval for MAC lung disease. Arikayce is the only therapy with a formal FDA indication in this space, though its current label is limited to refractory patients who have failed at least six months of multidrug therapy. Culture conversion rates in the refractory setting, as reported in Insmed's earlier CONVERT trial, were lower than those observed in ENCORE, which enrolled treatment-naive patients. Cross-trial comparisons are limited by differences in study design, patient populations, and disease severity, but the Month 6 culture conversion rate of approximately 88% in ENCORE appears numerically higher than rates typically reported with standard oral multidrug regimens alone in published observational cohorts.

Insmed plans to file a supplemental NDA with the FDA and submit data to Japan's PMDA in the second half of 2026, seeking both traditional approval for the existing refractory indication and potential label expansion to newly diagnosed MAC lung disease patients. The company also intends to present the full ENCORE dataset at a future medical congress.

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