- Question
- Can inclisiran, a small interfering RNA targeting PCSK9 given at infrequent intervals, lower LDL cholesterol in adults with heterozygous familial hypercholesterolemia?
- Design
- Phase 3, randomized 1:1, double-blind, placebo-controlled trial of 482 adults. Subcutaneous injections were given on days 1, 90, 270 and 450.
- Population
- Adults with heterozygous familial hypercholesterolemia and elevated LDL cholesterol. Median age was 56 years, 47% were men, and mean baseline LDL cholesterol was 153 mg/dL.
- Intervention
- Inclisiran sodium 300 mg subcutaneously on days 1, 90, 270 and 450, i.e., a twice-yearly dosing schedule after the initial dose.
- Control
- Matching placebo (saline) injected subcutaneously on the same schedule.
- Primary outcome
- Two primary endpoints: percent change in LDL cholesterol from baseline to day 510, and time-adjusted percent change in LDL cholesterol between day 90 and day 540.
- Results
- At day 510, LDL cholesterol fell by 39.7% with inclisiran and rose by 8.2% with placebo, a between-group difference of -47.9 percentage points (95% CI, -53.5 to -42.3; P<0.001). The time-adjusted change between days 90 and 540 was -38.1% versus +6.2%, a difference of -44.3 percentage points (95% CI, -48.5 to -40.1; P<0.001).
- Safety
- Adverse events and serious adverse events were similar in the two groups.
- Conclusion
- In adults with heterozygous familial hypercholesterolemia, inclisiran significantly lowered LDL cholesterol compared with placebo, with an infrequent dosing regimen and an acceptable safety profile.
- Why it matters
- It showed that an infrequently dosed PCSK9-targeting therapy can robustly lower LDL cholesterol in a high-risk population, broadening the options beyond monoclonal antibodies that require more frequent administration.
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 14, 2026