Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial
Authors' conclusion
In this trial, lerodalcibep, a novel anti-PCSK9 small binding protein, dosed monthly and stable at ambient temperatures significantly reduced LDL-C in patients with CVD or at high risk of atherosclerotic cardiovascular disease with a safety profile similar to placebo.
Study context
- Population
- Adults on maximally tolerated statin with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL with cardiovascular disease (CVD) or ≥100 mg/dL at high risk of CVD811 (88%) completed
- Participants
- 922 adults
- Comparison
- Lerodalcibep vs placebo
- Primary endpoint
- Percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52 (co-primary)
- Follow-up
- Week 52; mean of weeks 50 and 52
Methodological detailsdouble-blind, placebo-controlled, phase 3, 66 clinics in 11 countries, April 23, 2021, to November 15, 2023
- Double-blind
- Placebo-controlled
- Phase 3
- 66 clinics in 11 countries
- April 23, 2021, to November 15, 2023
Primary result
As reported in the abstract
Placebo-adjusted reduction in LDL-C
- Week 52, modified intention-to-treat (mITT); SE 2.2%
- mean placebo-adjusted reduction 56.2 %; P < 0.001
- Mean of weeks 50 and 52, mITT; SE 1.9%
- mean placebo-adjusted reduction 62.7 %; P < 0.001
- Week 52, ITT with washout imputation; SE 2.4%
- mean placebo-adjusted reduction 49.7 %; P < 0.001
- Mean of weeks 50 and 52, ITT with washout imputation; SE 2.2%
- mean placebo-adjusted reduction 55.3 %; P < 0.001
- Week 52, per-protocol; SE 2.3%
- mean placebo-adjusted reduction 60.3 %; P < 0.001
- Mean of weeks 50 and 52, per-protocol; SE 1.9%
- mean placebo-adjusted reduction 65.9 %; P < 0.001
Secondary outcomes
| Outcome | Lerodalcibep | Placebo | |
|---|---|---|---|
| LDL-C reduction ≥50% and recommended LDL-C targets achieved · during the study | 90% | Not reported in the abstract | Placebo: not reported in the abstract |
- LDL-C reduction ≥50% and recommended LDL-C targets achieved: 555 of 615
Safety
Injection site reactions
Treatment discontinuation
- Injection site reactions: 42 of 613 vs 1 of 307; graded mild or moderate
- Treatment discontinuation: 26 of 613 vs 14 of 307
Treatment-emergent adverse events
- Similar between lerodalcibep and placebo, except injection site reactions
Original publication
Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial. JAMA Cardiol. Published 1 September 2024. doi:10.
Summarised from the published abstract; every number is checked against it