lerodalcibep (LIB003) / LIB Therap, Hasten Biopharma - LARVOL DELTA

LIB Therapeutics Announces Results from Late Breaking Science Presentation at 2025 American Heart Association Meeting in New Orleans November 9, 2025 (Businesswire) - "Lerodalcibep demonstrated consistent long-term efficacy in those continued on the drug and was well tolerated, with no treatment related serious adverse events; 72-week primary endpoint; mean & absolute LDL-C reductions of 59.2% & 66.6 mg/dL respectively....LIB submitted a Biologic License Application (BLA) to the U.S. Food and Drug Administration (FDA) in December 2024, and received formal filing by FDA in February with an anticipated PDUFA date on target for mid December this year...Marketing Authorization Application was submitted to, and accepted by the European Medicines Agency in May with anticipated approval in June 2026."

EMA approval • FDA approval • Late-breaking abstract • P3 data • Cardiovascular • Dyslipidemia

Long-term Efficacy and Safety of Lerodalcibep in the Open-label 72-week Extension Study of Subjects Previously on Inclisiran or Lerodalcibep in the LIBerate-VI Trial (AHA 2025) - "Treatment with lerodalcibep demonstrated consistent long-term efficacy in those previously treated with the drug. Subjects switched from inclisiran to lerodalcibep had prolonged substantial additional LDL-C reductions and goal achievement, consistent with added inhibition of circulating free PCSK from non-hepatic synthesis."

Clinical • Metabolic Disorders • APOB

Lerodalcibep: Another Crucial Addition to the Dyslipidaemia Arsenal. (PubMed, Rev Cardiovasc Med) - No abstract available

Journal • Dyslipidemia

The evolving landscape of targets for lipid lowering: from molecular mechanisms to translational implications. (PubMed, Eur Heart J) - "Bempedoic acid inhibits ATP citrate lyase, the enzyme upstream of HMG-CoA reductase in the mevalonate pathway, offering an alternative to statins by selectively acting in the liver, minimizing muscle-related side effects. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors [evolocumab, alirocumab, inclisiran, lerodalcibep, and enlicitide decanoate (MK0616)] prevent LDLR degradation, while ezetimibe limits intestinal cholesterol absorption...Ongoing research into strategies to reduce Lp(a), primarily but not exclusively through antisense therapies, aims to demonstrate the cardiovascular benefits of targeting this lipoprotein. In summary, the field of targets for lipid and lipoprotein lowering is constantly evolving and offers new strategies for patients resistant to current therapies or with specific lipid profile abnormalities."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders • ANGPTL3 • APOB • LPL

LIBerate Kids: Randomized, Placebo-Controlled, Double-Blind, Phase 3b Study to Evaluate the Efficacy and Safety of Lerodalcibep in Children 6 to 17 Years, With Heterozygous FH (clinicaltrials.gov) - P3 | N=150 | Not yet recruiting | Sponsor: LIB Therapeutics LLC

New P3 trial • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders

Safety and effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition: an updated review. (PubMed, Curr Opin Lipidol) - "PCSK9i remain integral in ASCVD risk reduction, given their potent LDL-C-lowering effects, all while maintaining a favorable safety profile. The greatest benefits are observed in patients with AMI, particularly in multivessel disease. Despite high adherence, broader utilization is hindered by persistent challenges, including costs and complex authorization processes."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Myocardial Infarction

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American Heart Association Scientific Sessions. (PubMed, Curr Atheroscler Rep) - "Included studies assessed effects of intensive blood pressure control in patients with type 2 diabetes (BPROAD); decision support system for physicians to optimize early lipid lowering therapies after acute coronary syndrome (ZODIAC); efficacy and safety of zerlasiran, a short interfering RNA targeting lipoprotein(a) (ALPACAR); efficacy and safety of muvalaplin an oral disrupter of the assembly of lipoprotein(a) particles (KRAKEN); safety and efficacy of obicetrapib in patients with heterozygous familial hypercholesterolemia (BROOKLYN); efficacy and safety of lerodalcibep, a third generation PCSK9 inhibitor in heterozygous familial hypercholesterolemia subjects (LIBerate-HeFH_OLE); personalized app-based coaching to improve physical activity in patients with HFpEF compared to standard care (MyoMobile); semaglutide to improve cardiovascular outcomes in patients with a history of coronary artery bypass surgery and overweight or obesity (the SELECT trial); efficacy and..."

Journal • Review • Acute Coronary Syndrome • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Obesity • Pancreatitis • Type 2 Diabetes Mellitus

LIB Therapeutics Announces FDA Acceptance of Biologics License Application for Lerodalcibep to Lower LDL-Cholesterol Across Broad Patient Population (Businesswire) - "LIB Therapeutics Inc...today announced the U.S. Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) of Lerodalcibep to reduce low-density lipoprotein cholesterol (LDL-C) for the treatment of patients with atherosclerotic cardiovascular disease (ASCVD), or very high or high risk of ASCVD, and primary hyperlipidemia, including heterozygous, and those 10 years or older with homozygous familial hypercholesterolemia (HeFH / HoFH)...The FDA has set a Prescription Drug User Fee Act (PDUFA) action date of December 12, 2025. The FDA is not currently planning to hold an advisory committee meeting to discuss the application...The Lerodalcibep BLA is supported by a development program of 2,900 patients, including five global Phase 3 registration studies known collectively as the LIBerate program."

FDA filing • PDUFA • Cardiovascular • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia

A Study on Evaluating the Safety of HST101 in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=30 | Enrolling by invitation | Sponsor: Hasten Biopharmaceutical Co., Ltd. | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Dyslipidemia • Metabolic Disorders

A Study on Efficacy and Safety of HST101 in Chinese Patients with Hypercholesterolemia (clinicaltrials.gov) - P3 | N=210 | Recruiting | Sponsor: Hasten Biopharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Mixed Hyperlipidemia

Lerodalcibep and evolocumab for the treatment of homozygous familial hypercholesterolaemia with PCSK9 inhibition (LIBerate-HoFH): a phase 3, randomised, open-label, crossover, non-inferiority trial. (PubMed, Lancet Diabetes Endocrinol) - P3 | "The LDL cholesterol response was highly variable, but generally similar in patients treated with both lerodalcibep and evolocumab. Importantly, the study showed the inability to predict response based on genotyping, reinforcing the rationale for PCSK9 inhibition in all patients with homozygous familial hypercholesterolemia and continuing its use in responders."

Head-to-Head • Journal • P3 data • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pediatrics

LIB Therapeutics Announces Publication of Phase 3 Study of Lerodalcibep in Homozygous Familial Hypercholesterolemia (HoFH) in Lancet Diabetes & Endocrinology (Businesswire) - P3 | N=65 | NCT04034485 | Sponsor: LIB Therapeutics LLC | "Mean LDL-C reduction when averaged across all monthly visits was –9.1% with lerodalcibep and –10.8% with evolocumab. % LDL-C reduction at Week 12 was -12% with lerodalcibep and -11.5% with evolocumab, and at Week 24 (ITT analysis) was -4.9% with lerodalcibep and -10.3% with evolocumab. LDL-C responses were highly variable between patients, but the percent change from baseline for LDL-C over 24 weeks was similar in individual patients for both drugs... Importantly, genotyping and free PCSK9 suppression were not predictive of response. Both drugs were well tolerated, with no treatment-related serious adverse events. Injection site reactions were reported in one (2%) of 65 patients on lerodalcibep and 15 (24%) of 62 patients on evolocumab."

P3 data • Homozygous Familial Hypercholesterolemia

An up-to-date review of emerging biologic therapies for hypercholesterolemia. (PubMed, Expert Opin Biol Ther) - "In addition to the currently available monoclonal antibodies (mAbs) and small interfering RNA (siRNA), new mAbs and the adenectin lerodalcibep are promising therapies. The antisense oligonucleotide (ASO) and siRNA inhibitors of apoC3 and ANGPTL3 are effective in severe hypertriglyceridemia and homozygous familial hypercholesterolemia, respectively, and may prove to have wider applications. ASO and siRNA inhibitors of Lp(a) are currently in cardiovascular outcome studies."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • Severe Hypertriglyceridemia • ANGPTL3

LIB Therapeutics Submits a Biologic License Application to FDA for Lerodalcibep for the Treatment of Adults with Elevated LDL-Cholesterol (Businesswire) - "LIB Therapeutics Inc. (LIB)...announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of Lerodalcibep to reduce low-density lipoprotein cholesterol (LDL-C) for the treatment of patients with atherosclerotic cardiovascular disease (ASCVD), or very high or high risk of ASCVD, and primary hyperlipidemia, including heterozygous and homozygous familial hypercholesterolemia (HeFH / HoFH)....'As planned, the Lerodalcibep BLA has been submitted to the FDA, and we are now preparing a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for submission by mid-2025...'"

EMA filing • FDA filing • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia

Lerodalcibep A Novel ThirdGeneration Proprotein Convertase SubtilisinKexin Type 9 Inhibitor for Hypercholesteremia in Patients with Atherosclerotic Cardiovascular Disease (ASHP 2024) - No abstract available

Clinical • Atherosclerosis • Cardiovascular

Efficacy and Safety of Lerodalcibep, a Third Generation PCSK9 Inhibitor, in 703 Heterozygous Familial Hypercholesterolemia Subjects in the Open Label Extension Trial (AHA 2024) - "Despite treatment with statin in 91% (high intensity 71%) and ezetimibe in 52%, the mean (SD) LDL-C at baseline was 144.9 (61.9) mg/dL and mean apolipoprotein B 119.9 (39.3) mg/dL. Lerodalcibep 300 mg QM administered for up to 2 years in a large cohort of over 700 HeFH patients, significantly, persistently and consistently reduced LDL-C and other atherogenic lipids with no attenuation and good tolerability and safety. Over 70% of HeFH subjects were able to achieve currently recommended LDL-C targets."

Clinical • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Long-term Efficacy of Lerodalcibep in 1,468 Patients at Very High and High Risk for CVD in the 72 week Open-Label Extension Trial (AHA 2024) - " Mean age (range) was 63.9 (25 to 89) years, 37% female, 79% white, 18% black/multiracial, with 85.5% on statins, 18% on ezetimibe and 67% with CVD and 33% at very high or high risk for CVD. Lerodalcibep significantly and persistently reduced LDL-C with no attenuation in subjects with, or at very high or high risk for, CVD on maximally tolerated statin and other oral agents for >2 years with good adherence to self-dosing, tolerability and no new safety concerns identified. Lerodalcibep enabled nearly 90% of patients to achieve the new globally harmonized more stringent LDL-C goals."

Clinical

To evaluate the efficacy and safety of HST101 (Ledaceibup) in Chinese patients with hypercholesterolemia (ChiCTR) - P3 | N=210 | Not yet recruiting | Sponsor: Peking University First Hospital; Peking University First Hospital

New P3 trial • Dyslipidemia • Metabolic Disorders

LIBerate-VI: Trial to Evaluate Efficacy and Safety of LIB003 and Inclisiran in High-risk CVD Patients (clinicaltrials.gov) - P3 | N=166 | Completed | Sponsor: LIB Therapeutics LLC | Active, not recruiting ➔ Completed

Trial completion • Atherosclerosis • Dyslipidemia • Metabolic Disorders

LIBerate-OLE: Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction (clinicaltrials.gov) - P3 | N=2000 | Enrolling by invitation | Sponsor: LIB Therapeutics LLC | Trial completion date: Dec 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Jul 2025

Trial completion date • Trial primary completion date • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

A Study on Efficacy and Safety of HST101 in Chinese Patients With Hypercholesterolemia (clinicaltrials.gov) - P3 | N=210 | Not yet recruiting | Sponsor: Hasten Biopharmaceutical Co., Ltd.

New P3 trial • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Mixed Hyperlipidemia

Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease: A Randomized Clinical Trial. (PubMed, JAMA Cardiol) - P3 | "These results support long-term use of lerodalcibep in patients with CVD or at high risk of CVD who are unable to achieve adequate LDL-C reduction while receiving maximal tolerated statins alone. ClinicalTrials.gov Identifier: NCT04806893."

Clinical • Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American College of Cardiology Conference. (PubMed, Curr Atheroscler Rep) - "The LIBerate-HR trial showed the efficacy and safety of lerodalcibep, a subcutaneous injection that prevents binding of Pro-Protein Convertase Subtilisin/Kexin (PCSK) 9 to low-density lipoprotein (LDL)-receptors resulting in LDL-cholesterol (LDL-C) lowering in patients at very high risk or high risk of atherosclerotic CV disease (ASCVD). The AEGIS-II randomized patients with type 1 myocardial infarction (MI) with multivessel coronary artery disease and additional CV risk factors and found no benefit in major adverse CV events (MACE) with CSL112, an apolipoprotein A1 infusion shown to increase cholesterol efflux capacity. The Bridge-TIMI 73a trial showed a significant reduction in triglyceride (TG) levels with olezarsen, an antisense mRNA, in patients with moderate hyperTG with elevated CV risk...The VICTORIAN-INITIATE trial showed efficacy and safety in early use of inclisiran in patients with ASCVD who did not reach target LDL-C < 70 mg/dL despite maximally..."

Journal • Review • Atherosclerosis • Cardiomyopathy • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus • AKR1B1 • APOA1

Randomized, Double-blind, Placebo-controlled, Phase 3, Study To Evaluate Lerodalcibep Long-term Efficacy And Safety In Patients With, Or At Very-high Or High Risk, For Cardiovascular Disease On Stable Lipid-lowering Therapy (ACC 2024) - "There is no abstract associated with this presentation."

Clinical • Late-breaking abstract • P3 data • Cardiovascular

Randomized, Double-blind, Placebo-controlled, Phase 3, Study To Evaluate Lerodalcibep Long-term Efficacy And Safety In Patients With, Or At Very-high Or High Risk, For Cardiovascular Disease On Stable Lipid-lowering Therapy (ACC 2024) - "Abstract is embargoed at this time."

Clinical • Late-breaking abstract • P3 data • Cardiovascular