Response to PCSK9 Inhibition Based on LDL Receptor Function in Familial Hypercholesterolemia: A Nonrandomized Clinical Trial
Authors' conclusion
These findings suggest that lerodalcibep was associated with significantly and consistently reduced LDL-C in patients with HeFH, with response found to be independent of LDLR function of the pathogenic variant.
Study context
- Population
- Adults with heterozygous familial hypercholesterolemia (HeFH) requiring additional lipid-lowering therapy
- Participants
- 703 adults
- Outcome
- LDL-C reduction
- Follow-up
- Weeks 48 and 72
Methodological detailspredefined pooled subanalysis of an open-label phase 3 extension study, worldwide, single-group, open-label extension December 2020 to May 2025
- Predefined pooled subanalysis of an open-label phase 3 extension study
- Worldwide
- Single-group
- Open-label extension December 2020 to May 2025
Main finding
As reported in the abstract
Mean LDL-C reduction
| Group | Value | Week 72 mean reduction (SD) | Week 48 mean absolute change (SD) | Week 72 mean absolute change (SD) |
|---|---|---|---|---|
| Lerodalcibep | mean 50.3% (SD 28.9%) | 50.3% (28.7%) | −72.6 [50.5] mg/dL | −71.8 [48.0] mg/dL |
Lerodalcibep
Valuemean 50.3% (SD 28.9%)
Week 72 mean reduction (SD)50.3% (28.7%)
Week 48 mean absolute change (SD)−72.6 [50.5] mg/dL
Week 72 mean absolute change (SD)−71.8 [48.0] mg/dL
Further findings
Low-density lipoprotein cholesterol (LDL-C) response by LDLR variant functional activity
- LDL-C reduction independent of LDLR variant functional activity
- Monogenic FH variants in 455 (61.5%) of 740 genetically tested; 432 (95.7%) LDLR
LDL-C reduction ≥50% and atherosclerotic cardiovascular disease (ASCVD) risk-based LDL-C goal achieved
- Participants achieving both
- More than 70%
Original publication
Response to PCSK9 Inhibition Based on LDL Receptor Function in Familial Hypercholesterolemia: A Nonrandomized Clinical Trial. JAMA Cardiol. Published 1 June 2026. doi:10.
Summarised from the published abstract; every number is checked against it