anacetrapib (MK-0859) / Merck (MSD) - LARVOL DELTA

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

Suppression of inflammation via PCSK9 inhibition can improve outcome after cerebral ischemic injury (ISC 2025) - "For PCSK9 inhibition, PCSK9 inhibitor (evolocumab) or CETP inhibitor (anacetrapib [ANA]) were added, respectively. Stroke-induced micloglial activation was suppressed by PCSK9 inhibition (p<0.01; image3).Conclusions : Our study revealed that both of PCSK9 and SREBP2 up-regulation could be occurred following ischemic injury. Directly PCSK9 inhibition can improve neurological outcome via suppression of stroke-induced inflammation."

Cardiovascular • CNS Disorders • Inflammation • Vascular Neurology • MRC1 • PCSK9

Assessing lipid-lowering and plasma cholesteryl ester transfer protein activity of Centranthus longiflorus and β-Sitosterol following administration to triton WR1339- treated rats. (PubMed, Food Sci Nutr) - "After 7 days, ethanol extraction of CL plant, aqueous suspension of βS and anacetrapib was given to rats by oral gavage 1 h before the triton injection...Finally, CL extract and βS inhibited CETP, at which point βS was more effective. These findings showed that CL extract and βS reduce plasma lipid concentration and may have a hypolipidemic effect due to their anti-CETP properties."

Journal • Preclinical • Dyslipidemia

Obicetrapib exhibits favorable physiochemical and pharmacokinetic properties compared to previous cholesteryl ester transfer protein inhibitors: An integrated summary of results from non-human primate studies and clinical trials. (PubMed, Pharmacol Res Perspect) - "Anacetrapib, a cholesteryl ester transfer protein (CETP) inhibitor previously under development, exhibited an usually extended terminal half-life and large food effect and accumulated in adipose tissue. Obicetrapib shows no clinically relevant accumulation, is minimally affected by food, and has a mean terminal half-life of 131 h for the 10 mg dose. These data support once daily, chronic dosing of obicetrapib in Phase III trials for dyslipidemia management."

Journal • PK/PD data • Review • Dyslipidemia • Metabolic Disorders

Quantitation of anacetrapib in human and animal adipose by liquid chromatography with mass spectrometric detection. (PubMed, Bioanalysis) - "The assays were validated in the concentration ranges of 5-5000 ng/ml and 0.1-100 μg/ml. The anacetrapib concentrations in adipose tissue from preclinical and clinical studies were determined."

Journal • Dyslipidemia

Confounding association between plasma HDL-C levels and increased fracture risk: A correspondence. (PubMed, Health Sci Rep) - "The article emphasizes the need to reconsider HDL-C's traditional role as an indicator of cardiovascular health, particularly in light of medications like Statins and Anacetrapib that raise HDL-C levels...Practical implications involve incorporating fracture risk associated with high HDL-C into clinical considerations, alongside advocating lifestyle changes for optimal HDL-C levels. In summary, this study prompts a reevaluation of HDL-C's implications in clinical practice, demanding further investigation into the intricacies of this relationship."

Journal • Cardiovascular • Geriatric Disorders • Musculoskeletal Diseases • Orthopedics

Inhibition of Cholesteryl Ester Transfer Protein Contributes to the Protection of Ginsenoside Re Against Isoproterenol-Induced Cardiac Hypertrophy. (PubMed, Cureus) - "Methods Rats were intraperitoneally injected with ISO 30 mg/kg thrice daily for 14 consecutive days to induce cardiac hypertrophy, and these rats were treated with atorvastatin (ATC, 20 mg/kg) or Re (20 mg/kg or 40 mg/kg) once daily for three days in advance until the end of the experiment. Re improved cardiac hypertrophy mainly associated with the inhibition of mRNA level and protein expression of CETP, to an extent comparable to that of the classical CETP inhibitor, anacetrapib. Conclusions Our research found that CETP inhibition contributes to the protection of Re against ISO-induced cardiac hypertrophy, which provides evidence for the application of Re for cardiovascular disease treatments."

Journal • Cardiovascular • Dyslipidemia

Obicetrapib Does Not Accumulate in Adipose Tissue: Results from Studies in Man and Non-human Primates (NLA 2024) - "Background/Synopsis: Previous CETP inhibitors were highly lipophilic with logP of 7.2–9.2, leading to adipose tissue accumulation in the case of anacetrapib...A phase 1 trial administered doses of 1-25 mg to healthy humans, and 3, placebo-controlled, phase 2 studies in dyslipidemic humans administered obicetrapib (on background statin therapy) at 5 or 10 mg/d for 8 weeks (ROSE; n=120), 10 mg/d monotherapy or with ezetimibe for 12 weeks (ROSE2; n=119), and 2.5, 5, or 10 mg/d for 8 weeks (Japan; n=102)... In dedicated pre-clinical experiments and in clinical trials, obicetrapib shows no evidence of accumulation in adipose tissue or delayed elimination from the systemic circulation supporting once daily, chronic dosing of 10 mg."

Metabolic Disorders

Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis. (PubMed, J Cardiovasc Dev Dis) - "Our meta-analysis shows, for the first time, that CETPis are associated with reduced CVD-related mortality and MI."

Journal • Retrospective data • Review • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Dyslipidemia • Myocardial Infarction

CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice. (PubMed, JCI Insight) - "Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice...In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis."

Journal • Preclinical • Cardiovascular • Infectious Disease • Inflammation • Pneumococcal Infections • Pneumonia • Respiratory Diseases • Septic Shock • APOA1 • APOE • GLI2

CARDIOVASCULAR SAFETY PROFILE OF CHOLESTERYL ESTER TRANSFER PROTEIN INHIBITORS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF 17 RANDOMIZED CONTROLLED TRIALS (ACC 2024) - "Six trials examined dalcetrapib (n=23,057), 7 anacetrapib (n=33,643), two torcetrapib (n=16,255), one obicetrapib (n=66), and one evacetrapib (n=12092). The use of anacetrapib resulted in a lower incidence of MACE and MI events than placebo. Besides its robust effects on LDL and HDL cholesterol, it has an acceptable safety profile."

Retrospective data • Review • Cardiovascular

The Evolving Role of Cholesteryl Ester Transfer Protein Inhibition Beyond Cardiovascular Disease. (PubMed, Pharmacol Res) - "Initially, the potential effect on cardiovascular events of CETP inhibitors was hypothesized to be mediated by their ability to increase HDL cholesterol, but, based on evidence from anacetrapib and the newest CETP inhibitor, obicetrapib, it is now understood to be primarily due to reducing LDL cholesterol and apolipoprotein B. Nevertheless, evidence is also mounting that other roles of HDL, including its promotion of cholesterol efflux, as well as its apolipoprotein composition and anti-inflammatory, anti-oxidative, and anti-diabetic properties, may play important roles in several diseases beyond cardiovascular disease, including, but not limited to, Alzheimer's disease, diabetes, and sepsis. In fact, certain HDL subclasses may, in contrast, be beneficial for treating the retinal cholesterol accumulation that occurs with AMD. This review describes the latest biological evidence regarding the relationship between HDL and CETP inhibition for Alzheimer's disease,..."

Journal • Age-related Macular Degeneration • Alzheimer's Disease • Cardiovascular • CNS Disorders • Diabetes • Dyslipidemia • Infectious Disease • Macular Degeneration • Metabolic Disorders • Ophthalmology • Retinal Disorders • Septic Shock • Type 2 Diabetes Mellitus • APOB

Impact of New Cardiovascular Events on Quality of Life and Hospital Costs in People With Cardiovascular Disease in the United Kingdom and United States. (PubMed, J Am Heart Assoc) - P3 | "We assess the immediate- and longer-term impacts of new vascular and nonvascular events on quality of life (QoL) and hospital costs among participants in the REVEAL (Randomized Evaluation of the Effects of Anacetrapib Through Lipid Modification) trial in secondary prevention...Unique identifier: ISRCTN48678192; https://www.clinicaltrialsregister.eu. Unique identifier: 2010-023467-18."

HEOR • Journal • Cardiovascular • Cerebral Hemorrhage • Congestive Heart Failure • Heart Failure • Hematological Disorders • Myocardial Infarction • Oncology

"Not true. At 4th yr FU, anacetrapib --> a 9% RRR (1% ARR) in 1ary outcome due not to a ⬆️ in HDLc but rather to a 26 mg/dl lower LDLc. No harm, BTW. For obvious reasons it was never marketed, but the REVEAL study once again confirmed the CTT meta analysis. Hence, high hopes w/OBI" (@pabeda1)

Retrospective data

Structure-based mechanism and inhibition of cholesteryl ester transfer protein. (PubMed, Curr Atheroscler Rep) - "CETP inhibitors, including torcetrapib, dalcetrapib, evacetrapib, anacetrapib and obicetrapib, were designed and evaluated in phase III clinical trials for the treatment of ASCVD or dyslipidemia. Insights into the structural-based CETP-lipoprotein interactions can unravel CETP inhibition machinery, which can hopefully guide the design of more effective CETP inhibitors that combat ASCVD. Individual-molecule 3D structures of CETP bound to lipoproteins provide a model for understanding the mechanism by which CETP mediates lipid transfer and which in turn, guide the rational design of new anti-ASCVD therapeutics."

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

"CETPi anacetrapib in REVEAL makes 5 mechanisms?" (@fipco)

"And anacetrapib group had higher all cause and cardiovascular deaths and had no clinical utility after phase 3." (@DanClintonRN)

Clinical • P3 data • Cardiovascular

Alternaria alternata Causing Brown Spot Disease on Walnut in Xinjiang, China. (PubMed, Plant Dis) - "ITS, endoPG and H3 sequences had 99.81% (1/535 nt difference), 99.78% (1/448 nt difference) and 100% (0/417 nt difference) homology with homologous sequences of A. alternata strains (KP124306 [ITS], KP124006 [endoPG], MK085979 [H3]), respectively...Forest Research. 30(6):1004-1008."

Journal • Infectious Disease

Dalcetrapib and anacetrapib increase apolipoprotein E-containing HDL in rabbits and humans. (PubMed, J Lipid Res) - "New Zealand White rabbits receiving atorvastatin were treated with dalcetrapib or anacetrapib. Overall, in rabbits and humans, CETPi increase large apo E-containing HDL particle concentration, which can interact with hepatic LDLr. The catabolism of these particles may depend on an adequate level of LDLr to contribute to reverse cholesterol transport."

Journal • Preclinical • Dyslipidemia • APOE

Cholesteryl Ester Transfer Protein Inhibition Reduces Major Adverse Cardiovascular Events by Lowering Apolipoprotein B Levels. (PubMed, Int J Mol Sci) - "Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction."

Adverse events • Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • APOB

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease. (PubMed, Eur Heart J) - No abstract available

Clinical • Journal • Atherosclerosis • Dyslipidemia

Long-term safety and efficacy of anacetrapib in patients with atherosclerotic vascular disease. (PubMed, Eur Heart J) - P3 | "Trials of lipid-modifying agents need to have sufficiently long treatment and follow-up durations to fully assess the benefits and harms of treatment."

Clinical • Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Myocardial Infarction • Oncology

CETP-inhibitors: from HDL-C to LDL-C lowering agents? (PubMed, Cardiovasc Res) - "The use of CETP inhibitors is supported by genetic evidence from Mendelian randomization studies, showing that LDL-C lowering by CETP gene variants achieves equal ASCVD risk reduction as LDL-C lowering through gene proxies for statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors. Whereas first-generation CETP inhibitors (torcetrapib, dalcetrapib) were mainly raising HDL-C or had off-target effects, next generation CETP inhibitors (anacetrapib, evacetrapib) were also effective in reducing LDL-C and apoB and have been proven safe...The newest-generation CETP inhibitor obicetrapib, specifically designed to lower LDL-C and apoB, has achieved significant reductions of LDL-C up to 45%. Obicetrapib, about to enter phase III development, could become the first CETP inhibitor as add-on therapy for patients not reaching their guideline LDL-C targets."

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

[VIRTUAL] Obicetrapib Lowers LDL-C in Patients Taking High Intensity Statins: Results From Rose Clinical Trial (AHA 2021) - "This was confirmed in REVEAL; by lowering LDL-C, anacetrapib was associated with a reduction in cardiovascular events. Obicetrapib at doses of 5 and 10 mg produced robust decreases in LDL-C, ApoB and Non-HDL-C and increases in HDL-C compared to placebo in patients treated with high intensity statins and was safe and well tolerated."

Clinical • Cardiovascular • APOB

Long-term Benefits and Harms Associated With Genetic Cholesteryl Ester Transfer Protein Deficiency in the General Population. (PubMed, JAMA Cardiol) - "The study first tested whether a CETP allele score was associated with morbidity and mortality, when scaled to genetically lower levels of non-high-density lipoprotein (HDL) cholesterol (ie, 17 mg/dL), corresponding to the reduction observed for anacetrapib vs placebo in the Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial...Per 1 million person-years, the projected 1916 more AMD events associated with genetically higher levels of HDL cholesterol was similar to the 1962 fewer events of cardiovascular mortality and myocardial infarction combined associated with genetically lower levels of non-HDL cholesterol. This study suggests that genetic CETP deficiency, mimicking pharmacologic CETP inhibition, was associated with a lower risk of cardiovascular morbidity and mortality, but with a markedly higher risk of AMD."

Clinical • Journal • Age-related Macular Degeneration • Alzheimer's Disease • Cardiovascular • CNS Disorders • Coronary Artery Disease • Dementia • Heart Failure • Ischemic stroke • Macular Degeneration • Myocardial Infarction • Ophthalmology • Peripheral Arterial Disease • Retinal Disorders