Prevention & lipidsRandomised controlled trial
Lepodisiran — A Long-Duration Small Interfering RNA Targeting Lipoprotein(a)
- Randomised controlled trial
- placebo-controlled
- dose-ranging
Authors' conclusion
Lepodisiran reduced mean serum concentrations of lipoprotein(a) from 60 to 180 days after administration.
Study context
- Population
- Participants with elevated lipoprotein(a) (median baseline 253.9 nmol/L)1:2:2:2:2 randomisation
- Participants
- 320 participants
- Comparison
- Lepodisiran vs placebo
- Primary endpoint
- Placebo-adjusted time-averaged % change from baseline in serum lipoprotein(a)
- Follow-up
- Day 60 to day 180
Primary result
As reported in the abstract
Placebo-adjusted time-averaged % change in lipoprotein(a)
Each group vs placeboPlacebo-adjusted change, percentage points (95% CI)
16 mg
−40.8(−55.8 to −20.6)
96 mg
−75.2(−80.4 to −68.5)
Pooled 400 mgboth 400-mg groups pooled
−93.9(−95.1 to −92.5)
Further findings
| Outcome | placebo-adjusted change (percentage points) (95% CI) | |
|---|---|---|
| Placebo-adjusted time-averaged % change in lipoprotein(a) · day 30 to day 360 — 16 mg vs Placebo | −41.2 (−55.4 to −22.4) | |
| Placebo-adjusted time-averaged % change in lipoprotein(a) · day 30 to day 360 — 96 mg vs Placebo | −77.2 (−81.8 to −71.5) | |
| Placebo-adjusted time-averaged % change in lipoprotein(a) · day 30 to day 360 — 400 mg–placebo vs Placebo | −88.5 (−90.8 to −85.6) | |
| Placebo-adjusted time-averaged % change in lipoprotein(a) · day 30 to day 360 — 400 mg–400 mg vs Placebo | −94.8 (−95.9 to −93.4) | |
| −100−50050Difference, percentage points (linear scale) |
Safety
| Outcome | Values |
|---|---|
| Injection-site reactions (dose-dependent, generally mild) | Highest lepodisiran dose 12% |
- Injection-site reactions (dose-dependent, generally mild): up to 12% (8 of 69)
Serious adverse events
- Participants with serious adverse events (none deemed related to lepodisiran or placebo)
- 35
Original publication
Lepodisiran — A Long-Duration Small Interfering RNA Targeting Lipoprotein(a). N Engl J Med. Published 30 March 2025. doi:10.1056/nejmoa2415818
Summarised from the published abstract; every number is checked against it