Insmed (INSM) Study result summary

Study design and patient population

• ENCORE was a phase IIIb, double-blind, randomized controlled trial enrolling 425 adults with newly diagnosed or recurrent non-cavitary MAC lung infection, untreated for their current infection.

• Patients were randomized 1:1 to receive ARIKAYCE plus azithromycin and ethambutol or placebo plus the same background regimen for 12 months, followed by a 3-month observation period.

• Baseline characteristics were well balanced between arms, including age, sex, region, and disease history, with randomization stratified by region and prior MAC infection.

• The primary endpoint was change in Respiratory Symptom Score (RSS) at Month 13, using a validated patient-reported outcome tool; secondary endpoints included culture conversion at multiple time points and durable conversion at Month 15.

Efficacy results

• Statistically significant improvement in RSS at Month 13 for ARIKAYCE (17.77 points) vs. control (14.66 points), with a 3.11-point difference (p=0.0299).

• Symptom improvement persisted and increased at Month 15 (4.8-point difference, p=0.0015), three months off treatment.

• At Month 13, 82.4% of ARIKAYCE patients achieved culture conversion vs. 55.6% in control (p<0.0001); durable conversion at Month 15 was 76.2% vs. 47.6% (p<0.0001).

• ARIKAYCE outperformed control across all thresholds for meaningful within-patient RSS change and achieved earlier and more durable culture conversion at every measured timepoint.

• Median time to culture conversion was faster with ARIKAYCE (month 2) vs. control (month 3), hazard ratio 2.03 (p<0.0001).

Safety and tolerability

• No new or unexpected safety signals observed; safety profile consistent with known ARIKAYCE data.

• Most common adverse events (>10%) in ARIKAYCE arm: dysphonia, cough, fatigue, dyspnea, nausea, headache.

• Bronchospasm (23.0% vs 11.8%) and hypersensitivity pneumonitis (2.3% vs 0%) were more frequent with ARIKAYCE.

• Discontinuation rate for ARIKAYCE was 18.3%, lower than previous studies but higher than control; over 90% of patients completed the study in both arms.

• No deaths were considered related to ARIKAYCE or placebo; serious adverse event rates were 14.1% (ARIKAYCE) vs. 11.3% (control).