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

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

LONG-TERM EFFICACY AND SAFETY OF LERODALCIBEP IN HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (ACC 2024) - "Participants were dosed in clinic monthly through week 12 after which they were able to self-dose and be seen every 12 weeks. Overall mean age (range) was 52.8 (18-79) years, 51.3% female, 86% white and 14% South Asian, multiracial or black, with 88% on statins, 50.6% on ezetimibe and mean (SD) LDL-C of 153.4 (67.0) mg/dL. Lerodalcibep dosed monthly significantly and persistently reduced LDL-C, apo-B and Lp(a) in HeFH subjects with no attenuation and with a safety profile similar to placebo."

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

LIB Therapeutics and Partner Hasten Biopharmaceuticals Announce Lerodalcibep Clinical Trial Application Acceptance by the Center for Drug Evaluation at the National Medical Products Administration in China (Businesswire) - "LIB Therapeutics, Inc....today announced that its regional partner in China, Hasten Biopharmaceuticals Co, Ltd. (Hasten), has received notification of acceptance for the clinical trial application for Lerodalcibep by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) in China....'We are preparing our own Lerodalcibep BLA submission to the FDA, to be followed by MAA submission to EMA...'"

New trial • Cardiovascular

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7. (PubMed, Cardiovasc Diabetol) - "Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials...Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials...Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • ABCA1 • ACACA • ACSL3 • BMP2 • CD36 • COL1A1 • CPT1A • CTGF • EHHADH • HMGB1 • IFNA1 • IL1B • IL6 • MALT1 • RUNX2 • SCARB1 • SMAD7 • TCF7L2 • TNFA

PCSK9-directed therapies: an update. (PubMed, Curr Opin Lipidol) - "Long-term inhibition of PCSK9 with monoclonal antibodies is safe and conveys sustained cardiovascular benefit. Novel strategies to inhibit PCSK9 function such as orally available drugs, RNA targeting, and one-time treatment with gene editing may further enhance the therapeutic armamentarium and enable novel preventive strategies."

Journal • Cardiovascular

LIBerate-FH: Study to Assess the Efficacy and Safety of LIB003 in HeFH Patients on Oral Lipid Therapy Needing Further LDL-C Reduction (clinicaltrials.gov) - P3 | N=478 | Completed | Sponsor: LIB Therapeutics LLC | Active, not recruiting ➔ Completed | Trial completion date: May 2023 ➔ Dec 2023 | Trial primary completion date: Apr 2023 ➔ Jul 2023

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