- ORION-10 trial showed that semiannual inclisiran, a small interfering ribonucleic acid, produced potent, durable, low-density-lipoprotein cholesterol (LDL-C) reductions in patients with high-risk atherosclerotic cardiovascular disease (ASCVD) taking lipid-lowering therapies.
Why this matters
- Inclisiran's mechanism of action, different from current medications, suggests it may be good adjunctive therapy when additional LDL-C reduction is required.
- Semiannual injection may improve adherence.
- Patients ≥18 years, ASCVD with LDL-C ≥70 mg/dL on maximally tolerated statin doses ± ezetimibe.
- Randomly assigned to inclisiran 300 mg (n=781) or placebo (n=780) injection on days 1, 90, 270, 450.
- Groups well-balanced at baseline for age (median 66-67 years), LDL-C (105 mg/dL), sex, comorbidities, LDL-C-lowering medications.
- At day 540 (90 days after last dose), mean LDL-C decreased 56 mg/dL on inclisiran vs 1 mg/dL increase on placebo (P<.00001>
- LDL-C-lowering of >50 mg/dL at 3 months and durable through 18 months. Inclisiran vs placebo, P<.00001 at all time points.>
- Safety equivalent to placebo.
- Adverse events (AEs):
- Diabetes: inclisiran, 15%; placebo, 14%.
- Transient injection-site reactions: inclisiran, 2.6%; placebo, 0.9%.
- No differences in serious AEs.
- No liver, kidney, muscle, or platelet toxicity.
- Study funded by The Medicines Company.
- Inclisiran effect on other lipids unknown.
- Unknown adherence with infrequent dosing.
- Unknown long-term safety and effectiveness.
- Unknown clinical outcome rates with or vs statins alone.