The global Phase 3 LIBerate-CVD study with 922 patients was a randomized, double-blind, placebo-controlled trial to evaluate Lerodalcibep 52-week efficacy and safety in patients with a history of cardiovascular disease or at very high risk, for CVD on stable lipid-lowering therapy. The co-primary efficacy endpoints were the percent change from baseline in LDL-C at Week 52 and the mean of Weeks 50 and 52. Secondary outcomes included achievement of EAS / ESC LDL-C targets, and other lipid and apolipoproteins changes.
Patients were randomized 2:1 to a single 300 mg once-monthly, subcutaneous dose of Lerodalcibep or placebo for 52 weeks. Approximately 85% of participants had CVD, and 30% were female. Mean baseline LDL-C was 102 mg/dL (2.64 mmol/L), despite 85% of patients on statins and 15% on ezetimibe.
Results:
Co-primary endpoint achieved with Lerodalcibep: significant and persistent LDL-C reductions over 52 weeks of 62% (61 mg/dL, 1.61 mmol/L) at Week 52 and 69.4% (70 mg/dL, 1.81 mmol/L) at mean of Weeks 50 and 52 (P<0.0001).
During the study, 94% of all patients achieved the more stringent ESC and now global, lipid targets of ≥50% reduction in LDL-C from baseline and LDL-C <55 mg/dL (1.4 mmol/L)
Lerodalcipeb was well tolerated. Treatment-emergent adverse events were similar between Lerodalcibep and placebo, with the most common being mild to moderate injection site reactions, and no difference in discontinuations: Lerodalcibep (4.2%) vs placebo (3.6%)
Lerodalcibep was not associated with in vivo active ADAs or NAbs. There was no attenuation of either free PCSK9 suppression or LDL-C efficacy
“LIBerate-CVD is the final key registration-enabling trial of our global Phase 3 LIBerate program for Lerodalcibep,” said Evan Stein, MD, PhD, Chief Scientific Officer at LIB Therapeutics. “The LIBerate program enrolled a diverse global patient population with CVD, at very high and high risk for CVD, heterozygous and homozygous familial hypercholesterolemia (FH) to support a broad label upon approval. We could not have successfully carried out these global trials without the dedication and enthusiasm of the many investigators and patients around the world.”
The LIBerate-VI study was a randomized, open-label, study comparing efficacy and safety of Lerodalcibep to inclisiran in patients with, or at very high risk for CVD, on high intensity statin requiring additional LDL-C reduction at Day 270 (9 months). The trial was conducted in 21 centers in France, Germany, Norway, Spain and UK, with patients randomized 1:1 to Lerodalcibep 300 mg monthly or inclisiran 284 mg on Day 1 and 90.
Primary efficacy endpoints were the percent LDL-C change from baseline at Day 270. Secondary outcomes included achievement of EAS / ESC LDL-C targets, and other lipid and apolipoprotein changes. Of the 166 patients randomized, 160 completed the trial. Approximately 50% of the patients had CVD, 32% were female and 45% had HeFH. Mean baseline LDL-C was 112 mg/dL (2.85 mmol/L) despite nearly all patients on high intensity statins and ~45% on ezetimibe. Both Lerodalcibep and inclisiran were well tolerated with similar rates of adverse events.
At Day 270, mean LDL-C, was decreased from baseline with Lerodalcibep by 53% compared to 45.3% with inclisiran (P=0.0319) in the mITT population, and 55.4% and 45.4%, respectively, in the per-protocol population (P=0.005).
More patients achieved the EAS/ESC targets with Lerodalcibep than with inclisiran of >50% reduction in LDL-C from baseline (62% vs 50%) and LDL-C target of <55 mg/dL (1.4 mmol/L) (67% vs 50%). 58% of patients on Lerodalcibep versus 42% on inclisiran met both targets. Greater reductions in non-HDL-C (44.9% vs 38.2%), Apo B (38.2% vs 32.1%) and Lp(a) (26% vs 15.8%) were also seen with Lerodalcibep than with inclisiran (all P<0.05).
“These Lerodalcibep data provide additional evidence of a potential best in class profile including robust, sustained LDL-C lowering activity in a convenient and patient-friendly, once-monthly, single subcutaneous injection stable at ambient temperature that will not require refrigeration at home or in travel,” said David Cory, CEO of LIB Therapeutics. “We look forward to submitting a Biologics License Application to the Food and Drug Administration later this year, followed by a Marketing Authorization Application to the European Medicines Agency.”
About Lerodalcibep
Lerodalcibep is a novel, potent, small binding protein, third-generation PCSK9 inhibitor, and has been developed as a more convenient, once-monthly, single subcutaneous injection with long-ambient stability. In clinical trials, Lerodalcibep has demonstrated sustained LDL-C reductions and is expected to expand treatment options for the millions of patients around the world with atherosclerotic cardiovascular disease (ASCVD), and those at very high and high risk for ASCVD, including the 30 million individuals with more severe inherited high-cholesterol called familial hypercholesterolemia (FH).
The global Phase 3 LIBerate program enrolled a diverse population of over 2,700 patients with CVD, without CVD at very high and high risk for CVD, including heterozygous and homozygous familial hypercholesterolemia. Lerodalcibep was dosed once-monthly for up to 52 weeks in these key registration-enabling, placebo-controlled trials, and over 2,400 patients have continued in the 72-week open-label extension trial. LIB is preparing a biologics license application (BLA) for Lerodalcibep and plans for regulatory submission in 2024, followed by a Marketing Authorization Application to the European Medicines Agency.
About LIB Therapeutics Inc.
LIB Therapeutics is a privately-held, late-stage biopharmaceutical company dedicated to bringing Lerodalcibep to the millions of patients with cardiovascular disease and to the 30 million individuals with familial hypercholesterolemia (FH) around the world, who require additional large reductions in low density lipoprotein-cholesterol (LDL-C), despite maximally tolerated statins and other lipid lowering agents, to achieve LDL-C goals.
For more information, please visit: www.libtherapeutics.com.
