6/28/23, 11:45 PM ORION-10 Pathway Feedback Search Clinical Topics Home Studies ORION 10 ORION 10 Disease Disease Coronary artery disease Dyslipidemia Trial question What is the role of inclisiran in patients with increased low-density lipoprotein cholesterol despite statin therapy? Study design Multi-center Double blinded RCT Population Characteristics of study participants 31.0% female N = 1561 69.0% male 1561 patients (478 female, 1083 male) Inclusion criteria: patients with ASCVD 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=781 inclisiran (284 mg administered SC on day 1, day 90, day 270, and day 450) N=780 placebo (matching placebo administered SC) https://web.pathway.md/studies/recvbU2kFsXvESkim 1/2 6/28/23, 11:45 PM ORION-10 Pathway Primary outcome Significant increase in LDL cholesterol reduction at day 510 (51.3% vs. -1%; AD 52.3%, 95% CI 48.8 to 55.7) Secondary outcomes Significant increase in time-adjusted LDL cholesterol reduction from day 90 to 540 (51.3% vs. -2.5%; AD 53.8%, 95% CI 51.3 to 56.2) Significant increase in absolute LDL cholesterol level reduction at day 510 (56.2 mg/dL vs. 2.1 mg/dL; AD 54.1 mg/dL, 95% CI 50.9 to 57.4) Significant increase in absolute LDL cholesterol level reduction from day 90 to 540 (53.7 mg/dL vs. 0.4 mg/dL; AD 53.3 mg/dL, 95% CI 50.8 to 55.8) Safety outcomes No significant difference in adverse events. Significant difference in injection-site adverse events (2.6% vs. 0.9%). Conclusion In patients with ASCVD 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/recvbU2kFsXvESkim 2/2