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

Safety and efficacy of obicetrapib in dyslipidemia: systematic review and meta-analysis (ESC-WCC 2025) - No abstract available

Retrospective data • Review • Cardiovascular • Dyslipidemia

Efficacy of obicetrapib across the spectrum of background lipid lowering therapies-pooled analyses of the Broadway and Brooklyn randomised trials (ESC-WCC 2025) - No abstract available

Clinical • Cardiovascular

NewAmsterdam Pharma Announces Positive Topline Alzheimer’s Disease Data from BROADWAY Clinical Trial (GlobeNewswire) - P3 | N=2,530 | BROADWAY (NCT05142722) | Sponsor: NewAmsterdam Pharma | "Pre-specified analyses show that obicetrapib treatment leads to statistically significant and clinically meaningful reductions in the primary outcome measure of Alzheimer’s disease biomarker in both the full ITT population (p<0.002) and in ApoE4 carriers (p=0.0215), supporting the emerging link between CETP-inhibition and prevention of AD pathology....The Company plans to present the full results from the AD sub-study analysis in a Developing Topics oral presentation at the Alzheimer’s Association International Conference in Toronto at the end of July 2025."

P3 data: top line • Alzheimer's Disease

Comparative Efficacy of Anacetrapib and Obicetrapib: A Network Meta-Analysis of CETP Inhibitors (ENDO 2025) - "Anacetrapib and Obicetrapib significantly improve lipid profiles, with Obicetrapib excelling in HDL elevation and Anacetrapib demonstrating superior triglyceride reduction. Both agents are effective in reducing LDL and ApoB. These findings highlight their clinical potential in cardiovascular risk management and underscore the need for further evaluation in larger trials to confirm their safety and long-term efficacy."

Retrospective data • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

† Safety and efficacy of obicetrapib in patients with heterozygous familial hypercholesterolemia (NLA 2025) - P3 | "Conclusions Obicetrapib, as an adjunct to maximally tolerated lipid-modifying therapies, produced significant LDL-C lowering at day 84 with sustained effect through day 365 in patients with HeFH. Obicetrapib holds promise for patients with HeFH who are unable to attain their LDL-C treatment targets with available lipid-lowering agents."

Clinical • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOA1 • APOB

† Obicetrapib reduces atherosclerosis and vascular inflammation, mainly by reducing non-HDL-C, improves lesion stability adding to the beneficial effect of ezetimibe (NLA 2025) - "Analysis of covariance revealed that non-HDL-C exposure (p < 0.001) but not HDL-C exposure (p = 0.336) independently determined atherosclerotic lesion size. Conclusions Obicetrapib alone and in combination with ezetimibe prevents both local inflammation in the vessel wall as well as atherosclerosis development, and improves lesion stability, primarily attributable to a reduction in non-HDL-C levels."

Atherosclerosis • Cardiovascular • Dyslipidemia • Inflammation • Metabolic Disorders • APOA1 • APOB • APOE

Effect of Obicetrapib on New Onset Diabetes In Patients with Elevated LDL-C Receiving Maximally Tolerated Statin Therapy: Pooled Analyses of the Broadway and Brooklyn Trials (NLA 2025) - "Although obicetrapib led to greater LDL-C reductions than other CETPi, the effects of Obiceterapib on NoD were consistent with other CETPi. As risk of NoD accrues over time, larger and longer trials are needed to determine the full degree of potential protective effects of Obicetrapib on risk of NoD."

Clinical • Cardiovascular • Diabetes • Dyslipidemia • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOA1

303 Incremental Benefit of Atherogenic Cholesterol Reduction with Obicetrapib Administered with Moderate-Intensity Statins (NLA 2025) - "In both trials, obicetrapib was generally safe and well-tolerated when administered alone and in combination with statins. Conclusion A fixed dose combination of 10 mg obicetrapib with low-dose atorvastatin or rosuvastatin, which likely represents a more attractive treatment option to clinicians and patients than high-intensity statins, is expected to allow patients with dyslipidemia to substantially improve their lipid profile."

Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

† Obicetrapib significantly increases plasma and HDL-levels of lipophilic antioxidants (NLA 2025) - P2 | "Moreover, despite a relative decrease in lipophilic antioxidants in non-HDL, oxidized LDL (oxLDL) was decreased with obicetrapib. These data reflect obicetrapib's effect on non-HDL cholesterol and support the well-established evidence that HDL is a major protector against LDL oxidation."

Impact of the cholesteryl ester transfer protein inhibitor, Obicetrapib, on lipoprotein(a) levels: Pooled data from phase 3 clinical trials (NLA 2025) - "Methods A pooled analysis was performed evaluating the impact of obicetrapib on lipid levels which included the following clinical trials: (1) BROADWAY- evaluating obicetrapib and placebo in patients with heterozygous familial hypercholesterolemia (HeFH) or ASCVD, (2) BROOKLYN - evaluating obicetrapib and placebo in patients with HeFH and (3) TANDEM - evaluating the fixed dose combination of obicetrapib, ezetimibe, obicetrapib/ezetimibe and placebo in patients with or at high risk of ASCVD. The absolute reduction in Lp(a) was similar in patients with mildly elevated Lp(a) levels, who are unlikely to qualify for administration of RNA targeted Lp(a) lowering agents. The combined effects of obicetrapib on both LDL-C and Lp(a) have the potential to be an effective approach to lowering cardiovascular risk and is undergoing evaluation in a large cardiovascular outcomes trial."

Clinical • P3 data • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

† Obicetrapib alone and in combination with ezetimibe increases reverse cholesterol transport and does not affect VLDL production (NLA 2025) - "Obicetrapib alone and the combination with ezetimibe increased RCT, as indicated by an increased reappearance of the 14C-cholesterol label in HDL one-hour post-injection (+ 335% and + 237%, respectively) and an increased excretion of the label in feces collected after 48 hours post-injection (+ 13% (n.s.) and + 97%, respectively). Conclusions Combination of obicetrapib and ezetimibe induce net fecal sterol loss and increase reversed cholesterol transport."

Combination therapy • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB • APOE

Obicetrapib lowers LDL-cholesterol by substantially increasing LDL-ApoB clearance rates in humans (NLA 2025) - "Conclusions Obicetrapib reduced LDL-ApoB levels by substantially increasing the rate of LDL-ApoB clearance from circulation. These data complement the evidence from Mendelian randomization, preclinical and clinical outcome studies and conclusively support the mechanism of action of obicetrapib for LDL-C lowering as promoting the removal of circulating LDL particles."

APOB

† Low-dose obicetrapib significantly increases concentrations of lipophilic antioxidants, ApoE, and S1P in HDL subfractions (NLA 2025) - P2 | "Conclusions Obicetrapib treatment raised HDL2 cholesterol and ApoA1 and also shifted important lipophilic antioxidants, S1P, and ApoE to the HDL subfractions. These changes may have important therapeutic implications for CVD, AMD, and AD."

APOA1 • APOE

Cholesteryl Ester Transfer Protein Deficiency and Hyperalphalipoproteinemia. (PubMed, J Atheroscler Thromb) - "However, the association between ASCVD and ARMD risks in cases of very high HDL cholesterol level found in multifactorial hyperalphalipoproteinemia needs to be clarified on an etiological basis. The hurdles facing the development of CETP inhibitors are summarized, including a new result for obicetrapib."

Journal • Age-related Macular Degeneration • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Macular Degeneration • Ophthalmology • Retinal Disorders

LDL-cholesterol lowering with obicetrapib. (PubMed, Nat Rev Cardiol) - No abstract available

Journal

VERMEER: Evaluation of Obicetrapib on Antioxidant Levels in Plasma and HDL Particles of Healthy Volunteers (clinicaltrials.gov) - P2 | N=100 | Not yet recruiting | Sponsor: NewAmsterdam Pharma

New P2 trial

Obicetrapib-ezetimibe combination therapy for patients with atherosclerotic cardiovascular disease. (PubMed, Lancet) - No abstract available

Journal • Atherosclerosis • Cardiovascular

Fixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction (TANDEM): a phase 3, randomised, double-blind, placebo-controlled trial. (PubMed, Lancet) - P3 | "Combination therapy of obicetrapib and ezetimibe significantly reduced LDL cholesterol. This oral, single-pill therapy could improve LDL cholesterol management in patients with pre-existing or high risk for ASCVD."

Journal • P3 data • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia

Fixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction (TANDEM): a phase 3, randomised, double-blind, placebo-controlled trial (Lancet) - P3 | N=407 | TANDEM (NCT06005597) | Sponsor: NewAmsterdam Pharma | "Between March 4 and July 3, 2024, 407 participants were randomly assigned. The median age was 68·0 years (IQR 62·0–73·0) and 177 (43%) were female. Mean baseline LDL cholesterol was 2·4 mmol/L, 2·5 mmol/L, 2·6 mmol/L, and 2·5 mmol/L in the placebo (n=102), ezetimibe monotherapy (n=101), obicetrapib monotherapy (n=102), and FDC groups (n=102), respectively. At day 84, percent differences in LDL cholesterol reduction with the FDC were –48·6% (95% CI –58·3 to –38·9) versus placebo, –27·9% (–37·5 to –18·4) versus ezetimibe, and –16·8% (–26·4 to –7·1) versus obicetrapib. Obicetrapib monotherapy decreased LDL cholesterol by 31·9% (22·1 to 41·6) versus placebo."

P3 data • Dyslipidemia • Familial Hypercholesterolemia

NewAmsterdam Pharma Provides Corporate Update and Reports First Quarter Financial Results (GlobeNewswire) - "We are also progressing with regulatory interactions, including an expected EMA submission in the second half of the year by our partner Menarini....Additional data from BROADWAY, TANDEM, and BROOKLYN is expected to be presented and published over the next several months...PREVAIL Phase 3 trial. PREVAIL is a cardiovascular outcomes trial ('CVOT') evaluating obicetrapib in patients with a history of atherosclerotic cardiovascular disease ('ASCVD')...NewAmsterdam completed enrollment of over 9,500 patients in April 2024."

EMA filing • Enrollment status • P3 data • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia

Safety and Efficacy of Obicetrapib in Patients at High Cardiovascular Risk. (PubMed, N Engl J Med) - P3 | "Among patients with atherosclerotic cardiovascular disease or heterozygous familial hypercholesterolemia who were receiving maximum tolerated doses of lipid-lowering therapy and were at high risk for cardiovascular events, obicetrapib reduced LDL cholesterol levels by 29.9%. (Funded by NewAmsterdam Pharma; BROADWAY ClinicalTrials.gov number, NCT05142722.)."

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

LP(a): The new marker of high cardiovascular risk. (PubMed, Nutr Metab Cardiovasc Dis) - "Statins produce a modest increase, monoclonal PCSK9i and Inclisiran a modest decrease not sufficient to reduce significantly the risk associated to Lp(a). Only lipoprotein apheresis and obicetrapib, a CETP novel inhibitor, reduce respectively by 75% and 40% Lp(a) levels. To obtain a lifetime risk reduction of 50% similar to that achieved by reducing LDL-C of about 40 mg/dl, Lp(a) should be reduced of about 100 mg/dl. The ongoing trials on drugs such as ASO, SiRnas, assembly inhibitors and maybe in the future the gene editing could obtain these results."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Heart Failure • Ischemic stroke

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

Recent advances in immunotherapy targeting CETP proteins for atherosclerosis prevention. (PubMed, Hum Vaccin Immunother) - "CETP inhibitors, such as obicetrapib, represent a novel approach in immunotherapy to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) by targeting lipid metabolism. In addition, CETP vaccines are being explored as a novel strategy for the prevention and treatment of ASCVD by inducing the body to produce antibodies against CETP, which is expected to reduce CETP activity, thereby increasing high-density lipoproteins (HDL) levels. This paper provides a comprehensive overview of the structure of CETP, the mechanisms of lipid transfer and the progress of immunotherapy in the last decade, which provides possible ideas for future development of novel drugs and optimization of immunization strategies."

Journal • Review • Atherosclerosis • Cardiovascular • Metabolic Disorders

Lipid-lowering efficacy of obicetrapib: A comprehensive systematic review and meta-analysis. (PubMed, J Clin Lipidol) - "Obicetrapib is associated with significant reductions in key atherogenic lipoproteins, including LDL-C, ApoB, Non-HDL-C and Lp(a). Further investigation is needed to assess its impact on cardiovascular risk."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Dyslipidemia • APOB