July 13, 2024

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94% of Patients Achieve At Least 50% Reduction in “Bad Cholesterol” with New PCSK9 Inhibitor

94% of Patients Achieve At Least 50% Reduction in “Bad Cholesterol” with New PCSK9 Inhibitor



94% of Patients Achieve At Least 50% Reduction in “Bad Cholesterol” with New PCSK9 Inhibitor

Low-density lipoprotein cholesterol (LDL-C), commonly referred to as “bad cholesterol,” is a well-established modifiable risk factor for atherosclerosis.

Current international expert consensus recommends that cardiovascular disease patients aim for an LDL-C level of less than 55 mg/dl, and high-risk cardiovascular patients target an LDL-C level of less than 70 mg/dl, with an additional reduction of at least 50% from current levels.

However, in clinical practice, many patients do not reach these targets even with high-intensity statins combined with ezetimibe. Previous studies have indicated that patients who fail to meet these goals may benefit from PCSK9 inhibitors.

 

Lerodalcibep is a long-acting PCSK9 inhibitor. Partial results from the LIBerate-HR trial were presented at the 2024 American College of Cardiology (ACC) annual meeting, initially demonstrating its efficacy in lowering lipids.

Recently, the complete results of the LIBerate-HR trial were published in JAMA Cardiology, showing that lerodalcibep significantly reduced LDL-C levels by 56.3%, with 94% of patients achieving a lipid reduction of at least 50%.

 

94% of Patients Achieve At Least 50% Reduction in "Bad Cholesterol" with New PCSK9 Inhibitor

 

Study Details: The LIBerate-HR trial is a global, placebo-controlled, randomized, double-blind phase 3 clinical study. It included patients who:

  1. Had cardiovascular disease;
  2. Maintained stable dietary habits;
  3. Were on the maximum tolerated dose of statins plus other non-PCSK9 lipid-lowering medications;
  4. Had an LDL-C level of ≥70 mg/dl (general population) or ≥100 mg/dl (high-risk cardiovascular population) with triglycerides ≤400 mg/dl;
  5. Had not used PCSK9 inhibitors in the past year.

A total of 922 patients were randomly assigned in a 2:1 ratio to receive either lerodalcibep (monthly, 615 patients) or placebo (307 patients) for 48 weeks. At baseline, the average LDL-C level was 116.2 mg/dl, with 92.2% of patients on lipid-lowering drugs, 82.6% on statins (39.4% on high-intensity statins), and 16.6% on ezetimibe alone or combined with statins.

Primary Endpoints: The primary endpoints were the percentage change in LDL-C from baseline at week 52 and the average LDL-C level at weeks 50 and 52. For alignment with other PCSK9 inhibitor trials, the main endpoints were analyzed for the modified intent-to-treat (mITT) and per-protocol (PP) populations.

Results from the mITT analysis showed that at week 52, the LDL-C level in the lerodalcibep group decreased more significantly than in the placebo group (-56.33% vs. -0.15%, difference of -56.19%). The average LDL-C reduction at weeks 50 and 52 was also greater in the lerodalcibep group (-63.25% vs. -0.56%, difference of -62.69%).

Similar results were observed in the ITT and PP analyses.

Secondary Endpoints: Lerodalcibep outperformed the placebo on various secondary endpoints:

  • Apolipoprotein B: Decreased by 41.6% in the lerodalcibep group and increased by 1.4% in the placebo group (difference = -42.9%, 95% CI: -46.3% to -39.7%, P < 0.001);
  • Lipoprotein(a): Decreased by 21.6% in the lerodalcibep group and increased by 11.8% in the placebo group (difference = -33.4%, 95% CI: -38.7% to -28.0%, P < 0.001);
  • Plasma free PCSK9 levels: Decreased by over 90% in the lerodalcibep group compared to baseline, significantly more than in the placebo group (difference = -76%, 95% CI: -79.9% to -72.1%, P < 0.001);
  • Achievement of guideline-recommended LDL-C targets: 94% of patients in the lerodalcibep group had a ≥50% reduction in LDL-C, 90.9% reached LDL-C levels below 55 mg/dl or 70 mg/dl, and 90.2% met both targets, compared to 19.2%, 28.3%, and 16.0%, respectively, in the placebo group (all P < 0.001).

Safety: Safety profiles were comparable between the two groups, with 71.6% of lerodalcibep patients and 68.1% of placebo patients reporting adverse events, mostly mild to moderate.

In conclusion, this study demonstrates that lerodalcibep significantly lowers LDL-C levels in patients with cardiovascular disease or high-risk atherosclerotic cardiovascular disease, with a manageable safety profile. The findings support the use of lerodalcibep in high-risk patients who do not achieve target LDL-C levels despite maximum tolerated statin therapy.

94% of Patients Achieve At Least 50% Reduction in “Bad Cholesterol” with New PCSK9 Inhibitor

(source:internet, reference only)


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