Efficacy and Safety of Lerodalcibep in Patients at Very High and High Risk for Cardiovascular Disease - LIBerate-HR

Sep 30, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
LIB Therapeutics
Date Presented:
04/07/2024
Date Published:
07/03/2024
Date Updated:
09/30/2024
Original Posted Date:
04/07/2024
References

Contribution To Literature:

Highlighted text has been updated as of September 30, 2024.

The LIBerate-HR trial demonstrated that lerodalcibep reduces LDL-C levels in addition to statin therapy.

Description:

The goal of the trial was to evaluate lerodalcibep compared with placebo among patients with increased risk of cardiovascular disease (CVD). Lerodalcibep blocks pro-protein convertase subtilisin/kexin type 9 (PCSK9) binding to low-density lipoprotein (LDL)-receptors, thus preventing receptor degradation, which enhances LDL-C clearance and lowering of LDL-C levels.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Placebo

Patients with established or at high risk for CVD were randomized to lerodalcibep 300 mg dose in 1.2 mL subcutaneous injection (n = 615) vs. placebo (n = 307).

  • Total number of enrollees: 922
  • Duration of follow-up: 52 weeks
  • Mean patient age: 65 years
  • Percentage female: 45%
  • Percentage with diabetes: 45%

Inclusion criteria:

  • Established or at high risk for CVD
  • ≥18 years of age
  • On stable statin therapy

Other salient features/characteristics:

  • Mean LDL-C: 116 mg/dL

Principal Findings:

The primary outcome, change in LDL-C at 52 weeks, was -56.3% in the lerodalcibep group vs. -0.14% in the placebo group (p < 0.001).

Secondary outcomes:

  • Patients achieving ≥50% reduction in LDL-C: 94% with lerodalcibep vs. 19% with placebo
  • ≥1 adverse event leading to study drug withdrawal: 4.2% with lerodalcibep vs. 4.6% with placebo
  • Change in apolipoprotein B at 52 weeks: -43% for lerodalcibep vs. placebo
  • Change in lipoprotein(a) at 52 weeks: -33% for lerodalcibep vs. placebo

Interpretation:

Among patients with established or at high risk for CVD on stable statin therapy, lerodalcibep improves lipid control. Lerodalcibep vs. placebo was associated with a significant reduction in LDL-C and a greater proportion of patients achieving ≥50% reduction in LDL-C. The study drug was well tolerated with a similar proportion compared with placebo of adverse events leading to study drug withdrawal.

References:

Klug EQ, Llerena S, Burgess LJ, et al. Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial. JAMA Cardiol 2024;9:800-7.

Presented by Dr. Eric Klug at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024.

Clinical Topics: Atherosclerotic Disease (CAD/PAD), Acute Coronary Syndromes, Stable Ischemic Heart Disease

Keywords: ACC Annual Scientific Session, ACC24, Coronary Artery Disease, Novel Agents, Statins


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