6/28/23, 11:44 PM ORION-11 Pathway Feedback Search Clinical Topics Home Studies ORION 11 ORION 11 Disease Disease Coronary artery disease Dyslipidemia Trial question What is the role of inclisiran in patients with increased LDL cholesterol despite statin therapy? Study design Multi-center Double blinded RCT Population Characteristics of study participants 28.0% female N = 1617 72.0% male 1617 patients (457 female, 1160 male) Inclusion criteria: patients with ASCVD or an ASCVD risk equivalent who had increased LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose Key exclusion criteria: any uncontrolled or serious disease; NYHA class IV HF; uncontrolled cardiac arrhythmia; uncontrolled severe hypertension; active liver disease; treatment with monoclonal antibodies directed toward PCSK9 within 90 days before screening Interventions N=810 inclisiran (284 mg administered SC on day 1, day 90, day 270, and day 450) N=807 placebo (matching placebo administered SC) Primary outcome https://web.pathway.md/studies/rec9xaFk3N8ceYmPz 1/2 6/28/23, 11:44 PM ORION-11 Pathway Significant increase in LDL cholesterol reduction at day 510 (45.8% vs. -4%; AD 49.9%, 95% CI 46.6 to 53.1) Secondary outcomes Significant increase in time-adjusted LDL cholesterol reduction from day 90 to 540 (45.8% vs. -3.4%; AD 49.2%, 95% CI 46.8 to 51.6) Significant increase in absolute LDL cholesterol level reduction at day 510 (50.9 mg/dL vs. -1 mg/dL; AD 51.9 mg/dL, 95% CI 48.7 to 55) Significant increase in absolute LDL cholesterol level reduction from day 90 to 540 (48.6 mg/dL vs. 0.3 mg/dL; AD 48.9 mg/dL, 95% CI 46.5 to 51.4) Safety outcomes No significant differences in adverse events, serious adverse events. Significant difference in injection-site adverse events (4.7% vs. 0.5%). Conclusion In patients with ASCVD or an ASCVD risk equivalent who had increased LDL cholesterol levels despite receiving statin therapy at the maximum tolerated dose, inclisiran was superior to placebo with respect to LDL cholesterol reduction at day 510. Reference Kausik K Ray, R Scott Wright, David Kallend et al. Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol. N Engl J Med. 2020 Apr 16;382(16):1507-1519. Open reference URL https://web.pathway.md/studies/rec9xaFk3N8ceYmPz 2/2