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

Obicetrapib and ezetimibe enhance LDL receptor-mediated VLDL-clearance and regress atherosclerosis on atorvastatin background. (PubMed, J Lipid Res) - "In summary, obicetrapib alone and with ezetimibe reduces non-HDL-C by enhancing LDL receptor-mediated VLDL clearance, thereby synergistically reducing atherosclerosis. Triple treatment with obicetrapib, ezetimibe and atorvastatin regresses pre-existent atherosclerotic lesions."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOE

EFFICACY AND SAFETY OF OBICETRABIP IN REDUCING ATHEROGENIC LIPIDS: A SYSTEMATIC REVIEW AND DOSE RESPONSE META-ANALYSIS WITH TRIAL SEQUENTIAL ANALYSIS (ACC 2026) - "Obicetrapib improves lipid profiles with good safety. Dose modeling suggests 8 mg as optimal dose. This modeling-based insight refines previous findings by delineating a clearer therapeutic window."

Retrospective data • Review • APOA1 • APOB

SAFETY OF OBICETRAPIB: AN INTEGRATED POOLED PHASE III SAFETY ANALYSIS (ACC 2026) - "Obicetrapib was well tolerated, supporting its potential as an adjunct therapy for ASCVD or HeFH patients needing additional lipid-lowering options."

Clinical • P3 data • Age-related Macular Degeneration • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Hypertension • Macular Degeneration • Metabolic Disorders • Musculoskeletal Pain • Ophthalmology • Retinal Disorders

CETP INHIBITION WITH OBICETRAPIB PRESERVED KIDNEY FUNCTION IN PATIENTS AT HIGH CARDIOVASCULAR RISK: RESULTS FROM THE BROADWAY TRIAL (ACC 2026) - "In patients at high cardiovascular risk, CETP inhibition with obicetrapib preserved kidney function over a one-year period. These findings suggest that CETP inhibition may provide renoprotective effects, potentially through the restoration of HDL-mediated kidney-protective mechanisms."

Clinical • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Nephrology • Renal Disease

LIPID-LOWERING EFFICACY AND SAFETY OF OBICETRAPIB: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS (ACC 2026) - "As an add-on therapy to Ezetimibe, Obicetrapib yielded greater reduction in LDL (MD -51.99 [95% CI: -61.61 to -42.37]) and non-HDL (MD -50.32 [-55.42 to -45.21]). Obicetrapib was significantly associated with reductions in the lipid parameters, both as a monotherapy and as an adjunctive therapy."

Retrospective data • Acute Coronary Syndrome • Cardiovascular • Coronary Artery Disease • Heart Failure • Reperfusion Injury • APOA1 • APOB • APOE

Comparative efficacy and safety of obicetrapib vs bempedoic acid on top of statin therapy: A network meta-analysis. (PubMed, J Clin Lipidol) - "Among statin-treated patients requiring further LDL-C lowering, obicetrapib may represent an additional oral option to achieve the LDL-C target. Results should be interpreted in the context of currently available cardiovascular outcomes evidence, pending dedicated outcomes and long-term safety data."

Clinical • Journal • Retrospective data • Cardiovascular • Dyslipidemia

COST-EFFECTIVENESS OF OBICETRAPIB OR FIXED-DOSE COMBINATION AS AN ADJUNCT TO MAXIMALLY TOLERATED STATINS (ISPOR 2026) - "Many patients fail to achieve LDL-C targets, leaving them at increased cardiovascular risk. Adding obicetrapib alone or in combination with ezetimibe is cost-effective and can enable goal attainment, event reduction, and QALY gains."

Cost effectiveness • HEOR • Atherosclerosis • Cardiovascular • Dyslipidemia • Myocardial Infarction

Pharmacological management of elevated LDL in patients with hypercholesterolaemia and mixed dyslipidaemia. (PubMed, Expert Opin Pharmacother) - "Ezetimibe is the next recommended therapy to add, and bempedoic acid provides another oral drug that can be added or substituted for the statins. The injectable proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are the most effective drugs in reducing LDL-C, but their uptake has not met expectations because of issues of cost and patients' reluctance to take injection therapy. The oral PCSK9 inhibitors in development and obicetrapib appear safe and very effective and if approved they should provide useful alternatives for reaching LDL-C goals but the problem of long-term adherence to therapy will remain."

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

RUBENS: A 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 | Recruiting | Sponsor: NewAmsterdam Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • APOB

Lipid-modifying efficacy and safety of obicetrapib in high-risk cardiovascular patients: A systematic review and meta-analysis. (PubMed, Vasc Dis (Paris)) - "Obicetrapib substantially improved lipid profiles in high-risk ASCVD patients on maximally tolerated lipid lowering therapy, without increased short-term adverse events. However, further long-term randomized studies are needed to confirm sustained efficacy, long-term safety, and potential impacts on clinical cardiovascular outcomes."

Journal • Retrospective data • Acute Kidney Injury • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hypertension • Metabolic Disorders • Nephrology • Renal Disease • APOB

Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial. (PubMed, Nat Med) - P3 | "These findings suggest that obicetrapib is an effective therapy for additional lipid lowering in patients with heterozygous familial hypercholesterolemia. ClinicalTrials.gov registration: NCT05425745 ."

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

Obicetrapib in patients with heterozygous familial hypercholesterolemia: the BROOKLYN randomized clinical trial (Nature) - "For the primary endpoint, the change in LDL cholesterol from baseline to day 84, obicetrapib treatment resulted in a placebo-adjusted change in LDL cholesterol of −36.3% (95% confidence interval −42.2% to −30.4%, P < 0.0001). In analyses of secondary endpoints at day 84, treatment with obicetrapib resulted in placebo-adjusted reductions in apolipoprotein B of −24.4%, non-HDL cholesterol of −34.5% and lipoprotein(a) of −45.9%, as well as a placebo-adjusted increase in high-density lipoprotein cholesterol of +138.7%. Obicetrapib was well tolerated."

P3 data • Heterozygous Familial Hypercholesterolemia

Upcoming Milestones and Ongoing Trials (The Manila Times) - "...NewAmsterdam plans to announce additional data from these trials relating to obicetrapib and the FDC of obicetrapib plus ezetimibe during 2026...REMBRANDT Phase 3 trial...The trial is expected to complete enrollment of approximately 300 patients in 2026...Initiated in December 2025, the RUBENS trial will evaluate obicetrapib alone or in combination with ezetimibe in patients with type 2 diabetes or metabolic syndrome that require additional lowering of LDL-C despite treatment with available therapy. The trial is expected to enroll approximately 300 patients, with topline data expected by year end 2026....Additionally, NewAmsterdam expects to initiate a new clinical trial evaluating obicetrapib in early Alzheimer’s disease patients in 2026."

Clinical data • New trial • Alzheimer's Disease • Atherosclerosis • Cardiovascular • Dyslipidemia • Type 2 Diabetes Mellitus

Approval decisions from EMA, UK and Switzerland regulators for obicetrapib and obicetrapib/ezetimibe fixed dose combination expected in 2H26 (The Manila Times)

Approval • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia

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

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

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