Lipid-efficacy RCT · Eur Heart J 2023
LIBerate-HeFH trial
Long-term efficacy and safety of lerodalcibep in heterozygous familial hypercholesterolaemia: the LIBerate-HeFH trial.
The bottom line
In patients with heterozygous familial hypercholesterolaemia needing more LDL-C lowering, adding monthly subcutaneous lerodalcibep to therapy produced a large, highly significant LDL-C reduction versus placebo over 24 weeks with a safety profile similar to placebo aside from mild injection site reactions.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Compared with
- Placebo subcutaneous injection monthly
- People
- 478
- Who took part
- Heterozygous familial hypercholesterolaemia patients requiring additional LDL-C lowering; mean age (range) 53 (18-80) years, 51.7% female, mean (SD) baseline LDL-C 3.88 (1.66) mmol/L
- Design
- Randomized, placebo-controlled, Phase 3 trial (2:1 randomization)
- Follow-up
- 24 weeks
- Main question
- Per cent change from baseline in LDL-C at Week 24 and the mean of Weeks 22 and 24
Main result
Lerodalcibep reduced LDL-C vs placebo by -58.61 (3.25)% at Week 24 and -65.0 (2.87)% at mean of Weeks 22 and 24 (P < .0001 for all)
Effect on LDL cholesterol
Absolute reduction vs placebo of 2.08 (0.11) mmol/L (95% CI -2.30 to -1.87), percentage difference -58.61 (3.25)% at Week 24; and 2.28 (0.10) mmol/L (95% CI -2.47 to -2.09), percentage difference -65.0 (2.87)% at mean of Weeks 22 and 24 (P < .0001 for all)</ldl_effect> <parameter name="mortality_or_key_secondary">With lerodalcibep, 68% of subjects achieved both a reduction in LDL-C ≥ 50% and the recommended European Society of Cardiology LDL-C targets during the study.
Safety
Except for mild injection site reactions, treatment-emergent adverse events were similar between lerodalcibep and placebo.
In the trial's own words
“In 478 randomized subjects [mean age (range); 53 (18-80) years, 51.7% female, mean (SD) baseline LDL-C 3.88 (1.66) mmol/L], lerodalcibep reduced LDL-C, compared with placebo by an absolute amount of 2.08 (0.11) mmol/L [LS mean (SE); 95% confidence interval -2.30 to -1.87] with a percentage difference of -58.61 (3.25)% at Week 24 and by 2.28 (0.10) mmol/L (95% confidence interval -2.47 to -2.09) with a percentage difference of -65.0 (2.87)% at the mean of Weeks 22 and 24 (P < .0001 for all).”
Quoted from the abstract of Eur Heart J 2023, checked word for word against PubMed. PubMed 37639462 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Lerodalcibep (Lerochol)
Common questions
What did the LIBerate-HeFH trial find?
In patients with heterozygous familial hypercholesterolaemia needing more LDL-C lowering, adding monthly subcutaneous lerodalcibep to therapy produced a large, highly significant LDL-C reduction versus placebo over 24 weeks with a safety profile similar to placebo aside from mild injection site reactions.
Who was in LIBerate-HeFH?
478 people. Heterozygous familial hypercholesterolaemia patients requiring additional LDL-C lowering; mean age (range) 53 (18-80) years, 51.7% female, mean (SD) baseline LDL-C 3.88 (1.66) mmol/L.
What was LIBerate-HeFH's main result?
Lerodalcibep reduced LDL-C vs placebo by -58.61 (3.25)% at Week 24 and -65.0 (2.87)% at mean of Weeks 22 and 24 (P < .0001 for all)
How much did LDL cholesterol change in LIBerate-HeFH?
Absolute reduction vs placebo of 2.08 (0.11) mmol/L (95% CI -2.30 to -1.87), percentage difference -58.61 (3.25)% at Week 24; and 2.28 (0.10) mmol/L (95% CI -2.47 to -2.09), percentage difference -65.0 (2.87)% at mean of Weeks 22 and 24 (P < .0001 for all)</ldl_effect> <parameter name="mortality_or_key_secondary">With lerodalcibep, 68% of subjects achieved both a reduction in LDL-C ≥ 50% and the recommended European Society of Cardiology LDL-C targets during the study.
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