- Question
- Can inclisiran, a small interfering RNA targeting PCSK9 messenger RNA, produce sustained LDL cholesterol lowering in patients at high cardiovascular risk with elevated LDL cholesterol?
- Design
- Phase 2, multicenter, double-blind, placebo-controlled, multiple-ascending-dose trial with 501 randomized patients. Safety data were collected through day 210 and LDL cholesterol and PCSK9 data through day 240.
- Population
- Patients at high risk for cardiovascular disease (atherosclerotic cardiovascular disease, familial hypercholesterolemia or diabetes) with elevated LDL cholesterol.
- Intervention
- Subcutaneous inclisiran as a single dose of 200, 300 or 500 mg, or as two doses (days 1 and 90) of 100, 200 or 300 mg.
- Control
- Subcutaneous placebo (saline), given as a single dose or as two doses (days 1 and 90).
- Primary outcome
- Change from baseline in LDL cholesterol level at day 180.
- Results
- Inclisiran produced dose-dependent reductions in PCSK9 and LDL cholesterol. At day 180, least-squares mean LDL cholesterol reductions were 27.9 to 41.9% after a single dose and 35.5 to 52.6% after two doses (P<0.001 for all comparisons vs. placebo). The two-dose 300-mg regimen gave the greatest reduction, with 48% of those patients reaching an LDL cholesterol below 50 mg per deciliter (1.3 mmol per liter) at day 180.
- Safety
- Serious adverse events occurred in 11% of patients receiving inclisiran and in 8% receiving placebo. Injection-site reactions occurred in 5% of patients who received inclisiran.
- Conclusion
- Inclisiran lowered PCSK9 and LDL cholesterol levels in patients at high cardiovascular risk with elevated LDL cholesterol.
- Why it matters
- It was an early proof of concept that silencing hepatic PCSK9 synthesis with RNA interference can sustain LDL lowering with infrequent dosing, paving the way for the later clinical development of this strategy.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 15, 2026