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

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

NewAmsterdam Pharma Highlights 2024 Achievements and Outlines 2025 Strategic Priorities (GlobeNewswire) - "Additional data from BROADWAY, BROOKLYN, and TANDEM to be presented throughout 2025; expected to support global regulatory filings for obicetrapib, including EMA submission in 2H25 by our partner Menarini; Data from Phase 2 VINCENT trial expected by 2H25, which explores effect of obicetrapib alone and in combination with a PCSK9i on Lp(a)..."

P2 data • P3 data • Dyslipidemia • Familial Hypercholesterolemia • Metabolic Disorders

Menarini Group announces Positive Topline Data from Pivotal Phase 3…TANDEM Clinical Trials Evaluating Obicetrapib and the Fixed-Dose Combination Obicetrapib with Ezetimibe 10 mg (Canada Newswire) - P3 | N=407 | TANDEM (NCT06005597) | Sponsor: NewAmsterdam Pharma | "The co-primary endpoints in TANDEM were percent change from baseline in LDL-C of the fixed-dose combination compared to each monotherapy arm after 84 days and Obicetrapib 10 mg compared to placebo after day 84. Secondary endpoints incorporated percent changes from baseline in other biomarkers, including Lp(a), non-HDL-c and APO B. The TANDEM trial met all co-primary endpoints, including the fixed dose combination Obicetrapib with Ezetimibe achieving an LS mean reduction of 48.6% (p < 0.0001) compared to placebo at day 84...In the trial, the fixed-dose combination of Obicetrapib and Ezetimibe was observed to be well tolerated, with safety data comparable to placebo."

P3 data: top line • Familial Hypercholesterolemia

NewAmsterdam Pharma Announces Positive Topline Data from Pivotal Phase 3 BROADWAY Clinical Trial Evaluating Obicetrapib in Patients with Atherosclerotic Cardiovascular Disease and/or Heterozygous Familial Hypercholesterolemia (GlobeNewswire) - P3 | N=2532 | BROADWAY (NCT05142722) | Sponsor: NewAmsterdam Pharma | "NewAmsterdam Pharma Company N.V...today announced positive topline data from the Company’s Phase 3 BROADWAY clinical trial (NCT05142722) evaluating obicetrapib in adult patients with established atherosclerotic cardiovascular disease ('ASCVD') and/or heterozygous familial hypercholesterolemia ('HeFH')...'In 2025, we look forward to presenting additional BROADWAY and TANDEM data at upcoming scientific sessions'...The primary endpoint was the least-squares mean of the percent change in LDL-C from baseline to day 84 for obicetrapib 10 mg compared to placebo...The primary endpoint was achieved with statistical significance with an LDL-C reduction of 33% (p<0.0001)...Overall, obicetrapib was also observed to be well-tolerated, with safety results, including blood pressure, comparable to placebo. The treatment discontinuation rate for the obicetrapib arm was 11.1% versus 12.4% for placebo."

P3 data: top line • Cardiovascular • Heterozygous Familial Hypercholesterolemia

NewAmsterdam Pharma Announces Positive Topline Data from Pivotal Phase 3 TANDEM Clinical Trial Evaluating the Fixed-Dose Combination of Obicetrapib 10 mg and Ezetimibe 10 mg in Patients with ASCVD or ASCVD Risk Factors and/or HeFH (GlobeNewswire) - P3 | N=407 | (TANDEM) NCT06005597 | Sponsor: NewAmsterdam Pharma | "NewAmsterdam Pharma Company N.V...today announced positive topline data from the Company’s Phase 3 TANDEM clinical trial (NCT06005597).TANDEM will support global regulatory filings for the 10 mg obicetrapib and 10 mg ezetimibe fixed-dose combination in adult patients with heterozygous familial hypercholesterolemia ('HeFH') and/or atherosclerotic cardiovascular disease ('ASCVD') or multiple ASCVD risk factors, whose LDL-C is not adequately controlled, despite being on maximally tolerated lipid-lowering therapy...The TANDEM trial met all co-primary endpoints, including the obicetrapib-ezetimibe fixed dose combination achieving an LS mean reduction of 48.6% (p < 0.0001) compared to placebo at day 84...In the trial, the fixed-dose combination of obicetrapib and ezetimibe was observed to be well tolerated, with safety results comparable to placebo."

P3 data • Atherosclerosis • Cardiovascular • Familial Hypercholesterolemia

Safety and Efficacy of Obicetrapib in Patients with Heterozygous Familial Hypercholesterolemia (AHA 2024) - "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 • Late-breaking abstract • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • APOA1 • APOB

VINCENT: Impact of Obicetrapib and Obicetrapib Plus Repatha on Lp(a) Levels (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: NewAmsterdam Pharma | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2025 ➔ Dec 2025 | Initiation date: Aug 2024 ➔ Nov 2024 | Trial primary completion date: Mar 2025 ➔ Oct 2025

Combination therapy • Enrollment open • Trial completion date • Trial initiation date • Trial primary completion date • Dyslipidemia • Metabolic Disorders

A Study to Evaluate Drug-Drug Interactions of Obicetrapib Tablets and Ezetimibe Tablets in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=94 | Completed | Sponsor: NewAmsterdam Pharma | Active, not recruiting ➔ Completed

Trial completion

REMBRANDT: A CCTA Imaging Trial to Evaluate the Effect of Obicetrapib/Ezetimibe on Coronary Plaque (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: NewAmsterdam Pharma | Not yet recruiting ➔ Recruiting

Enrollment open • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia

Cholesteryl ester transfer protein inhibition: a pathway to reducing risk of morbidity and promoting longevity. (PubMed, Curr Opin Lipidol) - "At present, there is robust clinical evidence to support the benefits of reducing CETP activity for ASCVD risk reduction, and plausibility exists for the promotion of longevity by reducing risks of several other conditions. An ongoing large clinical trial program of the latest potent CETP inhibitor, obicetrapib, is expected to provide further insight into CETP inhibition as a therapeutic target for these various conditions."

Clinical • Journal • Review • Age-related Macular Degeneration • Alzheimer's Disease • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Dementia • Diabetes • Dyslipidemia • Macular Degeneration • Metabolic Disorders • Nephrology • Ophthalmology • Renal Disease • Retinal Disorders • Type 2 Diabetes Mellitus • APOB

TANDEM: Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies (clinicaltrials.gov) - P3 | N=407 | Completed | Sponsor: NewAmsterdam Pharma | Active, not recruiting ➔ Completed

Trial completion • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders

BROADWAY: Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies (clinicaltrials.gov) - P3 | N=2532 | Completed | Sponsor: NewAmsterdam Pharma | Trial primary completion date: Dec 2023 ➔ Sep 2024

Trial primary completion date • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • CRP

BROOKLYN: Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies. (clinicaltrials.gov) - P3 | N=354 | Completed | Sponsor: NewAmsterdam Pharma | Trial primary completion date: Jul 2023 ➔ May 2024

Trial primary completion date • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders

A Study to Evaluate Drug-Drug Interactions of Obicetrapib Tablets and Ezetimibe Tablets in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=94 | Active, not recruiting | Sponsor: NewAmsterdam Pharma | Recruiting ➔ Active, not recruiting

Enrollment closed

Obicetrapib Targets all Atherogenic Lipoproteins Beyond LDL-C (CMHC 2024) - "ROSE1 (n=120) and ROSE2 (n=119) were phase II trials of obicetrapib on top of high-intensity statins for 8 or 12 weeks and TA-8995-203 (n=102) was a phase II trial of obicetrapib on top of atorvastatin 10/20 mg or rosuvastatin 5/10 mg for 8 weeks in Japanese participants. By reducing atherogenic lipoproteins beyond LDL-C, obicetrapib monotherapy on top of statins and in combination with ezetimibe represents a promising therapy to address residual lipoprotein-related risk for CVD on top of currently available LDL-C-lowering therapies."

Cardiovascular • Dyslipidemia • ROS1

Obicetrapib Demonstrates Significant Reductions of Lp(a) on Top of High-Intensity Statins (CMHC 2024) - "In ROSE1 120 subjects received 5 or 10 mg obicetrapib or placebo; in ROSE2 119 received 10 mg obicetrapib, 10 mg obicetrapib + 10 mg ezetimibe or placebo. Obicetrapib 10 mg on top of high-intensity statin significantly lowered Lp(a) by 57% vs. placebo in a pooled analysis, a substantially greater reduction than with proprotein convertase subtilisin kexin type 9 inhibitors (15-30%), niacin (30%) or other CETP inhibitors (25%)."

Cardiovascular • Dyslipidemia • ROS1

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

BROADWAY: Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies (clinicaltrials.gov) - P3 | N=2532 | Completed | Sponsor: NewAmsterdam Pharma | Active, not recruiting ➔ Completed

Trial completion • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • CRP

A Study to Evaluate Drug-Drug Interactions of Obicetrapib Tablets and Ezetimibe Tablets in Healthy Adult Subjects (clinicaltrials.gov) - P1 | N=94 | Recruiting | Sponsor: NewAmsterdam Pharma | Not yet recruiting ➔ Recruiting

Enrollment open

Evaluating obicetrapib as an emerging treatment for patients with dyslipidemia: a game changer? (PubMed, Expert Opin Pharmacother) - "Obicetrapib is a potent CETP inhibitor, with a demonstrated ability to lower levels of apoB and LDL-C as monotherapy and in addition to high intensity statin therapy. The ultimate impact of obicetrapib on cardiovascular events will be evaluated by ongoing clinical trials."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders • APOB

Evaluate the Pharmacokinetics of a Combined Oral Contraceptive (COC) With and Without Obicetrapib (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: NewAmsterdam Pharma | Recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ Apr 2024 | Trial primary completion date: Jul 2024 ➔ Apr 2024

Trial completion • Trial completion date • Trial primary completion date