LIB Therapeutics Presents Successful 52-Week Lerodalcibep Trial at ACC 2024

LIB Therapeutics Inc., a privately-owned biopharmaceutical firm, has unveiled positive outcomes from two pivotal studies on Lerodalcibep, its innovative third-generation PCSK9 inhibitor designed to reduce LDL-cholesterol levels. These findings were presented at the American College of Cardiology's 2024 event held in Atlanta, Georgia.

The Phase 3 LIBerate-HR study, which included 922 participants, was a randomized, double-blind, placebo-controlled trial. It aimed to assess the 52-week efficacy and safety of Lerodalcibep in patients with cardiovascular disease or those at significant risk while on stable lipid-lowering therapy. The study's co-primary goals were to measure the percentage change in LDL-C levels at Week 52 and the average of Weeks 50 and 52. Secondary goals encompassed additional lipid and apolipoprotein metrics, free PCSK9 levels, and the achievement of LDL-C targets.

Participants were divided into two groups, with one receiving a monthly 300 mg subcutaneous dose of Lerodalcibep and the other a placebo, over the course of 52 weeks. Approximately half of the participants were identified as very-high or high risk for primary prevention, and nearly 50% were female. Despite the majority of patients already on statins and a significant percentage on ezetimibe, the mean baseline LDL-C was around 116 mg/dL.

The results were promising, with Lerodalcibep achieving its co-primary endpoint, showing significant and sustained reductions in LDL-C levels by 56% at Week 52 and 62% on average at Weeks 50 and 52. Over 90% of patients met the new, stricter ESC targets, which include a reduction of at least 50% in LDL-C from baseline and recommended LDL-C targets of less than 55 mg/dL for those with cardiovascular disease or at very high risk, and less than 70 mg/dL for those at high risk.

Furthermore, Lerodalcibep significantly reduced non-HDL-C by 47%, Apo B by 43%, and Lp(a) by 33%. The drug was well-tolerated, with treatment-emergent adverse events being comparable between the Lerodalcibep and placebo groups. The most common side effects were mild to moderate injection site reactions, with no difference in discontinuation rates. Importantly, Lerodalcibep did not show any association with active ADAs or Nabs, and there was no reduction in the suppression of free PCSK9 or LDL-C efficacy.

The Phase 3 LIBerate program, which included over 2,700 patients, enrolled a diverse group of individuals with cardiovascular disease, those at very high and high risk for the condition, and those with heterozygous and homozygous familial hypercholesterolemia. The program's key trials involved Lerodalcibep administered once a month for up to 52 weeks, with over 2,400 patients continuing into a 72-week open-label extension trial.

LIB Therapeutics is preparing to submit a biologics license application for Lerodalcibep and is planning for regulatory submission in 2024. The company is focused on providing novel, safe, and convenient subcutaneous and oral PCSK9 inhibitors to millions of patients with cardiovascular disease and those with familial hypercholesterolemia who require significant reductions in LDL-C levels beyond what is achievable with current treatments.

Lerodalcibep is a novel, potent, and small binding protein that offers the convenience of a once-monthly dose in a small injection volume with long-ambient stability. It is anticipated to broaden treatment options for patients with atherosclerotic cardiovascular disease and those at high risk, including the 30 million individuals with severe inherited high cholesterol known as familial hypercholesterolemia.