ORION-10
Trial question
What is the role of inclisiran in patients with increased LDL-C despite statin therapy?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
31.0% female
69.0% male
N = 1561
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).
Primary outcome
Reduction in LDL cholesterol at day 510
51.3%
-1%
51.3 %
38.5 %
25.6 %
12.8 %
0.0 %
-12.8 %
Inclisiran
Placebo
Significant
increase ▲
NNT = 1
Significantly greater reduction in LDL cholesterol 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).
Significantly greater reduction in absolute LDL cholesterol level 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 reduction in LDL cholesterol 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