obicetrapib (TA-8995) / Tanabe Pharma, NewAmsterdam Pharma, Menarini - LARVOL DELTA

From physiopathology to treatment of familial hypercholesterolemia: Existing and emerging pharmacotherapies. (PubMed, Pharmacol Rev) - "This includes established drugs such as proprotein convertase subtilisin/kexin type 9 inhibitors, inclisiran, lomitapide, and bempedoic acid. Emerging therapies include evinacumab, lerodalcibep, antisense oligonucleotide-based drugs, certain cholesteryl ester transfer protein inhibitors like obicetrapib, AZD8233, gemcabene, diacylglycerol O-acyltransferase-2 inhibitors, acyl-CoA:cholesterol acyltransferase-2 inhibitors, vupanorsen, volanesorsen, olezarsen, pelacarsen (TQJ230), olpasiran (AMG890), zerlasiran (SLN360), lepodisiran (LY3819469), and muvalaplin...Recent pharmacological advancements provide significant opportunities for successful low-density lipoprotein cholesterol management and control of FH. Although some of these agents are already used, several highly effective compounds are in development, heralding a promising future for FH treatment."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • APOB

LIPID-LOWERING EFFICACY AND SAFETY OF OBICETRAPIB: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (ACC 2026) - "Abstract is embargoed at this time."

Retrospective data • Acute Coronary Syndrome • Cardiovascular • Coronary Artery Disease • Heart Failure • Reperfusion Injury

CETP INHIBITION WITH OBICETRAPIB PRESERVED KIDNEY FUNCTION IN PATIENTS AT HIGH CARDIOVASCULAR RISK: RESULTS FROM THE BROADWAY TRIAL (ACC 2026) - "Abstract is embargoed at this time."

Clinical • Cardiovascular

Modulation of the cholesteryl ester transfer protein: new perspectives for the management of cardiovascular risk (PubMed, G Ital Cardiol (Rome)) - "Obicetrapib, a next-generation CETP inhibitor, has recently shown promising results in terms of efficacy and safety. This review critically examines the physiology of CETP, the negative outcomes of earlier CETP inhibitors, and the emerging evidence on obicetrapib, highlighting the potential role of this molecule in the treatment of hypercholesterolemia and in the secondary prevention of atherosclerotic cardiovascular disease."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

SAFETY OF OBICETRAPIB: AN INTEGRATED POOLED PHASE III SAFETY ANALYSIS (ACC 2026) - "Abstract is embargoed at this time."

Clinical • P3 data

Comparative efficacy of obicetrapib and anacetrapib in reducing low-density lipoprotein (LDL) levels: a network meta-analysis of clinical trials. (PubMed, Daru) - "Both agents effectively reduced LDL-C levels, with obicetrapib demonstrating superior efficacy compared to anacetrapib. Additionally, both treatments demonstrated favorable safety profiles. These findings underscore the potential of CETP inhibitors as promising therapeutic options for patients with dyslipidemia."

Clinical • Journal • Retrospective data • Review • Dyslipidemia • Metabolic Disorders • APOA1 • APOB • APOE

Key Expected 2026 Milestones... (Yahoo Finance) - "EMA approval decision for obicetrapib and obicetrapib/ezetimibe fixed dose combo expected in 2H26...REMBRANDT Phase 3 trial...The trial is expected to complete enrollment of approximately 300 patients in 2026....Additionally, NewAmsterdam expects to initiate a new clinical trial evaluating obicetrapib in early Alzheimer’s disease patients in 2026."

EMA approval • Enrollment status • New trial • Alzheimer's Disease • Cardiovascular • Dyslipidemia • Heterozygous Familial Hypercholesterolemia

Cholesteryl Ester Transfer Protein Inhibitors: State of the Science. (PubMed, Curr Cardiol Rep) - No abstract available

Journal • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders

Inhibition of cholesteryl ester transfer protein (CETP) with obicetrapib to reduce cardiovascular risk : BROADWAY Trial (PubMed, Inn Med (Heidelb)) - No abstract available

Journal • Cardiovascular

Efficacy of Obicetrapib Across the Spectrum of Background Lipid-Lowering Therapies: Pooled Analyses of the BROADWAY and BROOKLYN Randomized Trials. (PubMed, Eur J Prev Cardiol) - No abstract available

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders

Lipid-Lowering Efficacy and Adverse Events of CETP Inhibitor Combination Therapy: A Systematic Review and Network Meta-Analysis. (PubMed, J Cardiovasc Pharmacol) - "Our meta-analysis demonstrated that CETP inhibitor combination therapies offer distinct lipid-modulating benefits and safety profiles. The obicetrapib + ezetimibe + statin triple therapy showed superior comprehensive efficacy, while obicetrapib + statin exhibited the optimal safety. Evacetrapib + statin provided potent LDL-C reduction but had the poorest safety. These findings facilitate personalized treatment selection for dyslipidemia management."

Adverse events • Journal • Retrospective data • Dyslipidemia • Metabolic Disorders • APOA1 • APOB

Developing Topics. (PubMed, Alzheimers Dement) - P3 | "This very large biomarker study showed that obicetrapib significantly slowed the progression of AD biomarkers over a period of 1 year, particularly p -tau217 and p -tau217/Aβ42:Aβ40 ratio, with most pronounced effects in older individuals carrying the APOE4 allele. These findings support the dual therapeutic potential of obicetrapib in addressing both cardiovascular and neurodegenerative disorders. Given its effects on the early evolution of β-amyloid and tau pathology, obicetrapib represents a potential advancement in the prevention of AD, particularly in ApoE4 carriers who have an increased risks for both cardiovascular and AD pathologies."

Biomarker • Clinical • Journal • Alzheimer's Disease • Atherosclerosis • Cardiovascular • CNS Disorders • Dementia • Inflammation • Metabolic Disorders • APOE • Aβ42 • GFAP

Obicetrapib: A Novel Cholesterol Ester Transfer Protein Inhibitor. (PubMed, Cardiol Rev) - "Despite widespread use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, substantial atherosclerotic cardiovascular disease risk persists, especially in people with heterozygous familial hypercholesterolemia or elevated lipoprotein(a) [Lp(a)] levels. A 2025 pooled analysis offers initial evidence that major adverse cardiovascular events are reduced, as studied in the ongoing PREVAIL outcomes trial. This review covers CETP biology and tunnel mechanics, outcomes from earlier CETP inhibitor studies, obicetrapib's pharmacology, and current efficacy and safety data, and will clarify its potential place in lipid management today."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Obicetrapib for dyslipidemia with or without cardiovascular risk: A GRADE-assessed meta-analysis of randomized trials with trial sequential evidence. (PubMed, Diabetes Obes Metab) - "Obicetrapib provides substantial improvements in lipid parameters with a favourable short-term adverse events rate. These results support its role as a potential adjunctive lipid-lowering agent irrespective of ASCVD risk. Longer-term trials are warranted to confirm its durability, cardiovascular outcomes, and safety."

Journal • Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

CT.MDP.24: Closing the LDL Gap: Innovations, Access, and Adherence in Lipid-Lowering Therapy (AHA 2025) - "Discover the real-world impact of evolocumab, cost and utilization trends in under-treated populations, and access inequities driven by socioeconomic deprivation. With new evidence on emerging agents like bempedoic acid, obicetrapib, and zodasiran, this session brings together cutting-edge science and pragmatic solutions to confront one of cardiology's most persistent challenges: getting LDL down and keeping it there. This is not a CE accredited session."

Adherence • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders

Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies. (PubMed, Endocrinol Metab (Seoul)) - "While 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins, as well as ezetimibe, fibrates, and omega-3 fatty acids have established roles in lipid lowering, significant residual risk persists in many patients due to insufficient low-density lipoprotein cholesterol (LDL-C) reduction, elevated triglyceride-rich lipoproteins, and genetically determined elevations of lipoprotein(a) (Lp(a)). Clinical outcome trials have validated bempedoic acid, PCSK9 inhibitors, and icosapent ethyl, while large-scale programs are ongoing for obicetrapib, oral PCSK9 inhibitors, Lp(a)-targeted oligonucleotides, and ANGPTL3-directed RNA therapeutics. This review summarizes the mechanisms, pivotal trials, and clinical implications of innovative lipid-lowering therapies, highlighting how they may reshape future treatment algorithms for ASCVD prevention."

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

Lipoprotein(a) in Cardiovascular Diseases and Emerging Therapeutic Strategies. (PubMed, Cardiovasc Drugs Ther) - "As novel therapies advance and clinical guidelines evolve, Lp(a) is emerging as a central determinant in personalized cardiovascular care. The increasing emphasis on Lp(a) testing underscores its importance in risk stratification and future therapeutic decisionmaking."

Journal • Review • Atherosclerosis • Cardiovascular • Peripheral Arterial Disease

Efficacy of Obicetrapib on Lipid Parameters: A Meta-Analysis of Randomized Controlled Trials (AHA 2025) - "Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, with elevated low-density lipoprotein cholesterol (LDL-C) being a major modifiable risk factor; necessitating the development of additional lipid-lowering agents.Objective: This meta-analysis aimed to assess the lipid-modifying efficacy of obicetrapib across key atherogenic and protective lipid markers.We searched the Cochrane Central Registry of Controlled Trials, PubMed, Embase, Web of Science, and clinicalTrials.gov databases for all randomized controlled trials (RCTs) published up to May 2025 comparing sotatercept to placebo .Lipid outcomes evaluated included low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non–HDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Obicetrapib significantly improves atherogenic lipid profiles, including marked reductions in LDL-C and non–HDL-C, as well as a substantial..."

Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

Cholesteryl Ester Transfer Protein (CETP) Inhibition with Obicetrapib Produces Substantial Reductions in LDL Particles: Pooled Analysis of BROOKLYN and BROADWAY Phase 3 Clinical Trials (AHA 2025) - P3 | "Unlike statins, ezetimibe, PCSK9 inhibitors or other lipid-lowering therapies primarily affecting LDL particle removal, CETP inhibitors uniquely target exchange of cholesteryl esters for triglycerides between lipoproteins, leading to lower total and small LDL particle concentrations. Obicetrapib significantly reduces both total and small LDL particle numbers, particularly small LDL particles. These LDL particle number reductions exceeded the magnitude observed with conventional lipid-lowering therapies. The reductions in small LDL particles, known to be per particle more atherogenic, may translate into greater cardiovascular benefits than predicted from conventional LDL-C differences alone."

P3 data • Retrospective data • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders

Pharmacotherapy development and trends in lipidology: An expert discussion. (PubMed, J Clin Lipidol) - "Davidson and Dr. Maki also discuss the importance of implementing treatment early in life and of addressing multiple risk factors to reduce the risk of ASCVD and the associated burdens of morbidity and mortality."

Journal • Atherosclerosis • Cardiovascular • CNS Disorders • Coronary Artery Disease • Dyslipidemia • Heart Failure • Vascular Neurology

The two faces of cholesteryl ester transfer protein inhibitors. (PubMed, Curr Opin Lipidol) - "The therapeutic focus has shifted from HDL-C elevation to apoB lowering as the determinant of cardiovascular benefit. Obicetrapib shows promise, with ongoing trials designed to define its role in ASCVD management."

Journal • Review • Atherosclerosis • Cardiovascular • Diabetes • Metabolic Disorders • APOB

Efficacy and Safety of Obicetrapib in Dyslipidemia or Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analysis (AHA 2025) - "Obicetrapib significantly improved lipid parameters, notably reducing LDL-C, non-HDL-C, ApoB, Lp(a), and triglycerides, while increasing HDL-C and ApoA1, with a favorable and comparable safety profile."

Retrospective data • Review • Atherosclerosis • Back Pain • Cardiovascular • Dyslipidemia • Metabolic Disorders • Musculoskeletal Pain • APOA1 • APOB

Evaluating Lipid-Lowering Efficacy Of Obicetrapib: An Updated Meta-Analysis of Clinical Trials (AHA 2025) - "Introduction:Obicetrapib, a selective cholesteryl ester transfer protein (CETP) inhibitor, has demonstrated a reduction in low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB) as a monotherapy or in combination with ezetimibe. Obicetrapib demonstrated a significant reduction in atherogenic lipoproteins such as LDL-C, ApoB, and Non-HDL-C. Additionally, the HDL-C levels were significantly increased in the obicetrapib group. Further studies are needed to assess its impact on cardiovascular risk."

Retrospective data • Cardiovascular • Dyslipidemia • APOB

Obicetrapib in Patients with Dyslipidemia with or without Atherosclerotic Cardiovascular Disease Risk: A Meta-Analysis of Randomized Controlled Trials (AHA 2025) - "Our analysis shows that Obicetrapib, a selective CETP inhibitor, significantly improves lipid profiles in statin-treated patients with dyslipidemia, with or without ASCVD. It led to marked reductions in LDL-C, non-HDL-C, and apoB, and substantial increases in HDL-C. These effects significantly increased the achievement of LDL-C targets."

Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

Obicetrapib in combination with ezetimibe on top of atorvastatin regresses atherosclerotic plaque lesions in APOE*3-Leiden.CETP mice (AHA 2025) - "Obicetrapib + ezetimibe + atorvastatin triple combo treatment regressed lesion size as compared to baseline (-44%, p=0.032), thereby diminishing lesion severity and increasing the lesion-free area. Compared to atorvastatin monotreatment, triple combo treatment further reduced lesion size (-60%, p<0.001).ConclusionsHigh-intensive cholesterol-lowering triple combo treatment with obicetrapib + ezetimibe on top of atorvastatin robustly decreases non-HDL-C and regresses atherosclerotic lesion area in APOE*3Leiden.CETP mice."

Combination therapy • Preclinical • Atherosclerosis • Dyslipidemia • APOE