Prof Eric Quinton Klug, MBBCh, MMed, of the University of Witwatersrand, presented data on the novel PSCK9 inhibitor lerodalcibep today at the American College of Cardiology meeting in Atlanta, USA. 

LIBerate-HR (Efficacy and Safety of Lerodalcibep in Patients at Very-High and High Risk for CVD) was a phase 3, double-blind placebo-controlled 52-week trial. 

Patients from 11 countries were randomized 2:1 to monthly 1.2 mL sub-cutaneous (SC) lerodalcibep 300mg monthly or placebo for 52 weeks.  Co-primary efficacy endpoints were: % change from baseline in LDL-C at Week 52 and the mean of Weeks 50 and 52. Secondary outcomes included the achievement of LDL-C targets and other lipid and apolipoproteins change. 

Lerodalcipeb decreased LDL-C by 56% at week 52, and 62% at the mean of week 50 and 52; absolute reductions in LDL-C of 60.6 mg/dL and 74.5 mg/dL respectively.  Over 90% of Patients receiving lerodalcibep with very-high and high-risk CVD on maximally tolerated statins achieved both of the new stringent ESC targets of  ≥50% reduction in LDL-C from their current level and  the lower targets of <55 mg/dl with CVD or <70 mg/dl if high-risk CVD. Lerodalcibep also reduced non-HDL-C 47%, Apo B 43%, Lp(a) 33% and triglycerides 16%.

At one year, 824 patients (89%) had completed the study, with a similar dropout rate in both the lerodalcibep and placebo groups.  A mild or moderate injection site reaction, such as redness, itching or bruising, was the most common adverse event, (6.9%  lerodalcibep vs 0.3% placebo). 

“Lerodalcibep is a novel inhibitor of PCSK9, a protein in the liver that reduces the liver’s ability to clear LDL cholesterol from the circulation. PCSK9 inhibitors block the PCSK9 protein, enabling the liver to dispose of more LDL cholesterol, which in turn lowers blood levels of LDL cholesterol,” Klug said.  “Unlike existing approved PCSK9 inhibitors, lerodalcibep does not need refrigeration, is a smaller injectable volume and patients can administer their own injections.”

All the patients who participated in the LIBerate-HR trial are now receiving lerodalcibep and are being studied in an open-label ongoing assessment of the drug for another year. The study was funded by LIB Therapeutics, which manufactures lerodalcibep

Dr Stein, of LIB Therapeutics, stated the initial development program of lerodalcibep has been completed and additional study results will be presented later this year.  LIB Therapeutics is currently compiling data for submissions to both US and European regulatory authorities.   

References:

Radcliffe Cardiology, Dr Evan Stein, 7 Apr 2024, ACC.24: Lerodalcibep in Patients With High Risk For Cardiovascular Disease on Stable Lipid-Lowering Therapy, Accessed 7 April 2024. 

American College of Cardiology, 7 Apr 2024, Novel PCSK9 Inhibitor Cut LDL Cholesterol Levels by More Than Half [Press Release]