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

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

Safety and Efficacy of Obicetrapib for Atherogenic Lipid Reduction: A Systematic Review and Meta-Analysis. (PubMed, Cardiol Rev) - "Obicetrapib significantly improved the lipid profile, with marked reductions in atherogenic lipoproteins and increases in HDL-related parameters with no major safety concerns observed. These results support the inclusion of obicetrapib in broader lipid management approaches aimed at reducing cardiovascular risk."

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

Efficacy and safety of obicetrapib in patients with dyslipidemia: An updated meta-analysis of randomized controlled trials. (PubMed, Am J Prev Cardiol) - "Among patients with dyslipidemia and/or high cardiovascular risk, obicetrapib significantly reduces LDL-C, lipoprotein(a), apolipoprotein B, and non-HDL-C. No significant differences were observed in adverse events, supporting the favorable safety profile of obicetrapib."

Journal • Retrospective data • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • APOA1 • APOB

VERMEER: Evaluation of Obicetrapib on Antioxidant Levels in Plasma and HDL Particles of Healthy Volunteers (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: NewAmsterdam Pharma | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2026 ➔ Dec 2026 | Trial primary completion date: Apr 2026 ➔ Sep 2026

Enrollment open • Trial completion date • Trial primary completion date

RUBENS: A Randomized Phase 3 Study to Evaluate the Effect of Obicetrapib/Ezetimibe 10 mg Fixed-Dose Combination or Obicetrapib 10 mg Daily on Top of Guideline-Recommended Lipid-Lowering Therapy in Participants With Type 2 Diabetes and/or Metabolic Syndrome (clinicaltrials.gov) - P3 | N=300 | Not yet recruiting | Sponsor: NewAmsterdam Pharma

New P3 trial • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • APOB

Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p-tau217 levels in patients with cardiovascular disease. (PubMed, J Prev Alzheimers Dis) - P3 | "Obicetrapib significantly slowed AD biomarker progression over 12 months in participants with ASCVD, with the greatest effects in ApoE4 carriers. Among ApoE4/E4 participants, obicetrapib reduced p-tau217 levels by a placebo-adjusted 20.48 % and demonstrated consistent effects across multiple AD biomarkers. These findings represent the first demonstration of an oral intervention capable of reducing both beta-amyloid and tau pathology biomarkers in ApoE4 carriers, offering a potential preventive strategy for this high-risk population who currently have no effective prevention options. Future research will need to establish whether these biomarker changes translate to clinical benefits in dedicated AD prevention trials."

Journal • Alzheimer's Disease • Atherosclerosis • Cardiovascular • CNS Disorders • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Inflammation • Metabolic Disorders • APOE • Aβ42 • GFAP • NEFL • p-tau181

JCL Roundtable: Novel lipid management. (PubMed, J Clin Lipidol) - "Steven E. Nissen, Ann Marie Navar, Daniel Gaudet, and Kevin C. Maki who discussed novel lipid management options either recently approved or in development, including bempedoic acid, an adenosine triphosphate-citrate lyase inhibitor, the cholesteryl ester transfer protein inhibitor obicetrapib, and apolipoprotein (Apo) C3 inhibiting agents. The discussants describe the targets that are affected by these novel agents, including low-density lipoprotein cholesterol, lipoprotein(a), Apo B, Apo C3, triglycerides, remnant cholesterol, and chylomicron particles. Finally, the panelists expressed their excitement and optimism for these agents to become important elements of the toolbox for clinicians managing dyslipidemias."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

Decoding Structural Fingerprints to Design and Elucidate the Mechanism of Action of Prospective Cholesteryl Ester Transfer Protein Drugs. (PubMed, ChemMedChem) - "Molecular dynamics (MD) simulations of CETP in complexation with recently reported Obicetrapib with "good" fingerprints versus a clinically failed inhibitor, Torcetrapib shows superior inhibitory potential of the former due to stronger binding and better shape complementarity with the CETP hydrophobic tunnel. By leveraging the potentials of ML and MD simulations, this comprehensive study helps judicious pick of the right functional moieties for designing next generation CETP drugs targeting CVD."

Journal • Cardiovascular

Comparative Effectiveness of Cholesteryl Ester Transfer Protein (CETP) Inhibitors on Lipid Profiles in Adults With Hyperlipidemia: A Comprehensive Systematic Review and Frequentist Network Meta-Analysis of Randomized Controlled Trials. (PubMed, Clin Cardiol) - "CETP inhibitors, particularly anacetrapib and obicetrapib combined with statins, significantly improve lipid profiles, offering potential therapeutic benefits for hyperlipidemia management and cardiovascular risk reduction."

HEOR • Journal • Retrospective data • Review • Cardiovascular • Dyslipidemia

Menarini Group's Obicetrapib and Obicetrapib/Ezetimibe Marketing Authorisation Applications Accepted for Review by the European Medicines Agency (EMA) for the Treatment of adults with primary hypercholesterolaemia (heterozygous familial and non-familial) or mixed dyslipidaemia (PRNewswire) - "Obicetrapib: The submission is supported by results from the pivotal Phase 3 studies BROOKLYN and BROADWAY, conducted by NewAmsterdam Pharma....Obicetrapib/Ezetimibe:The submission is supported by results from the pivotal Phase 3 study TANDEM, conducted by NewAmsterdam Pharma..."

EMA filing • Dyslipidemia • Heterozygous Familial Hypercholesterolemia

Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. (PubMed, N Engl J Med) - No abstract available

Journal • Cardiovascular

Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Cardiovascular

Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. (PubMed, N Engl J Med) - No abstract available

Journal • Cardiovascular

Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. (PubMed, N Engl J Med) - No abstract available

Journal • Cardiovascular