Lipid-efficacy RCT · N Engl J Med 2020
ORION-10/11 trial
Two Phase 3 Trials of Inclisiran in Patients with Elevated LDL Cholesterol.
The bottom line
Twice-yearly inclisiran injections lowered LDL cholesterol by about 50% compared with placebo in statin-treated patients with atherosclerotic cardiovascular disease, with mostly mild injection-site reactions as the main safety difference.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Inclisiran 284 mg subcutaneous injection on day 1, day 90, and every 6 months thereafter
- Compared with
- Placebo (subcutaneous injection on same schedule)
- People
- 3,178
- Who took part
- Patients with atherosclerotic cardiovascular disease (ORION-10) or atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11) with elevated LDL cholesterol despite maximum tolerated statin therapy
- Design
- Two Phase 3, randomized trials (1:1 randomization to inclisiran or placebo); placebo-controlled
- Follow-up
- 540 days
- Main question
- Coprimary end points: placebo-corrected percentage change in LDL cholesterol from baseline to day 510, and time-adjusted percentage change in LDL cholesterol from baseline after day 90 up to day 540
Main result
Inclisiran reduced LDL cholesterol levels by 52.3% (95% CI, 48.8 to 55.7) in ORION-10 and 49.9% (95% CI, 46.6 to 53.1) in ORION-11 at day 510, with time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo)
Effect on LDL cholesterol
Placebo-corrected LDL-C reduction of 52.3% (95% CI, 48.8 to 55.7) at day 510 in ORION-10 and 49.9% (95% CI, 46.6 to 53.1) in ORION-11; time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6), respectively (P<0.001 for all comparisons vs. placebo)
Other results
Not reported in this abstract
Safety
Adverse events were generally similar between inclisiran and placebo groups in each trial, although injection-site adverse events were more frequent with inclisiran than with placebo (2.6% vs. 0.9% in ORION-10 and 4.7% vs. 0.5% in ORION-11); such reactions were generally mild, and none were severe or persistent
In the trial's own words
“At day 510, inclisiran reduced LDL cholesterol levels by 52.3% (95% confidence interval [CI], 48.8 to 55.7) in the ORION-10 trial and by 49.9% (95% CI, 46.6 to 53.1) in the ORION-11 trial, with corresponding time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo).”
Quoted from the abstract of N Engl J Med 2020, checked word for word against PubMed. PubMed 32187462 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Inclisiran (Leqvio)
Common questions
What did the ORION-10/11 trial find?
Twice-yearly inclisiran injections lowered LDL cholesterol by about 50% compared with placebo in statin-treated patients with atherosclerotic cardiovascular disease, with mostly mild injection-site reactions as the main safety difference.
Who was in ORION-10/11?
3,178 people. Patients with atherosclerotic cardiovascular disease (ORION-10) or atherosclerotic cardiovascular disease or an atherosclerotic cardiovascular disease risk equivalent (ORION-11) with elevated LDL cholesterol despite maximum tolerated statin therapy.
What was ORION-10/11's main result?
Inclisiran reduced LDL cholesterol levels by 52.3% (95% CI, 48.8 to 55.7) in ORION-10 and 49.9% (95% CI, 46.6 to 53.1) in ORION-11 at day 510, with time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6) (P<0.001 for all comparisons vs. placebo)
How much did LDL cholesterol change in ORION-10/11?
Placebo-corrected LDL-C reduction of 52.3% (95% CI, 48.8 to 55.7) at day 510 in ORION-10 and 49.9% (95% CI, 46.6 to 53.1) in ORION-11; time-adjusted reductions of 53.8% (95% CI, 51.3 to 56.2) and 49.2% (95% CI, 46.8 to 51.6), respectively (P<0.001 for all comparisons vs. placebo)
Related trials
- HAUSER-RCT (2020)In pediatric patients with heterozygous familial hypercholesterolemia already on lipid-lowering therapy, adding monthly evolocumab substantially lowered LDL cholesterol compared with placebo with a similar adverse event rate.
- ORION-9 (2020)In patients with heterozygous familial hypercholesterolemia, twice-yearly inclisiran injections significantly lowered LDL cholesterol compared with placebo, with a similar safety profile and a convenient infrequent dosing schedule.
- ODYSSEY OUTCOMES (2018)In post-ACS patients already on high-intensity statins, adding alirocumab reduced recurrent cardiovascular events and all-cause death compared with placebo.
- FOURIER-OLE (2022)Long-term evolocumab treatment after FOURIER maintained very low LDL-C with a persistently favorable safety profile over more than 8 years, and earlier initiation of evolocumab was associated with fewer cardiovascular events, including cardiovascular death, compared with delayed treatment start.
Get your LDL treated to a goal
Preval Health's protocols follow trials like this one. Licensed clinicians set your goal, prescribe and recheck until you reach it.
Get startedEducation only, not medical advice. Results describe the people in this trial and can differ for you. Talk with your clinician before starting or stopping any medicine. Back to all 106 trials.