Prevention & lipidsSecondary analysis
Effect on Lipoprotein(a) Oxidized Phospholipids of Lepodisiran, an Extended-Duration siRNA Targeting Lipoprotein(a)
- Post hoc analysis of a randomised controlled phase 2 trial
- placebo-controlled
- 66 global centres
Authors' conclusion
Lepodisiran produced sustained reductions in OxPL-apoB and OxPL-apo(a) levels that correlated with Lp(a) lowering.
Study context
- Population
- Participants of the lepodisiran phase 2 trial with oxidized phospholipids (OxPL) measured at baseline, day 240 and day 360of 320 trial participants
- Participants
- 213 participants
- Comparison
- Lepodisiran 16, 96 or 400 mg vs placebo
- Primary endpoint
- Placebo-adjusted % change from baseline in OxPL-apo(a) and OxPL-apoB
- Follow-up
- Day 240 and day 360
Primary result
As reported in the abstract
Placebo-adjusted geometric mean % change in OxPL-apo(a) and OxPL-apoB · day 240
Each group vs placeboEstimate (95% CI)
16 mgOxPL-apo(a)
geometric mean % change −21.9%(−45.0% to 11.0%)
96 mgOxPL-apo(a)
geometric mean % change −65.1%(−73.8% to −53.6%)
400 mgOxPL-apo(a)
geometric mean % change −94.2%(−95.7% to −92.2%)
16 mgOxPL-apoB
% change −39.5%(−51.2% to −25.0%)
96 mgOxPL-apoB
% change −76.9%(−80.6% to −72.5%)
400 mgOxPL-apoB
% change −88.5%(−90.4% to −86.3%)
Further findings
| Outcome | % change (95% CI) | |
|---|---|---|
| % change in OxPL-apo(a) and OxPL-apoB · day 360 — 16 mg vs Placebo · OxPL-apo(a) | −23.7% (−47.0% to 9.8%) | |
| % change in OxPL-apo(a) and OxPL-apoB · day 360 — 96 mg vs Placebo · OxPL-apo(a) | −41.6% (−56.4% to −21.6%) | |
| % change in OxPL-apo(a) and OxPL-apoB · day 360 — 400 mg vs Placebo · OxPL-apo(a) | −80.7% (−85.7% to −73.9%) | |
| % change in OxPL-apo(a) and OxPL-apoB · day 360 — 16 mg vs Placebo · OxPL-apoB | −30.6% (−46.4% to −10.2%) | |
| % change in OxPL-apo(a) and OxPL-apoB · day 360 — 96 mg vs Placebo · OxPL-apoB | −57.1% (−65.2% to −47.2%) | |
| % change in OxPL-apo(a) and OxPL-apoB · day 360 — 400 mg vs Placebo · OxPL-apoB | −79.9% (−83.8% to −75.2%) | |
| −100−50050Difference (linear scale) |
Baseline OxPL levels (all participants) · median baseline
- Median OxPL-apo(a), nmol/L (Q1, Q3: 105.1, 137.7)
- 122.0
- Median OxPL-apoB, nmol/L (Q1, Q3: 22.5, 36.2)
- 27.7
Correlations with Lp(a) and inflammation
- % change in OxPL-apo(a) correlated more closely than OxPL-apoB with % change in Lp(a)
- No significant correlation between changes in hs-CRP and OxPL
Original publication
Effect on Lipoprotein(a) Oxidized Phospholipids of Lepodisiran, an Extended-Duration siRNA Targeting Lipoprotein(a). J Am Coll Cardiol. Published 31 August 2026. doi:10.1016/j.jacc.2026.07.015
Summarised from the published abstract; every number is checked against it