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

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

Event Reduction With Obicetrapib: A Word Of Caution. (PubMed, J Am Coll Cardiol) - No abstract available

Journal • Cardiovascular

Obicetrapib and Cardiovascular Events: A Promising Signal in Need of Confirmation. (PubMed, J Am Coll Cardiol) - No abstract available

Journal • Cardiovascular

Impact of Obicetrapib on Major Adverse Cardiovascular Events in High-Risk Patients: A Pooled Analysis. (PubMed, J Am Coll Cardiol) - "Obicetrapib treatment associated with a reduction in coronary events, evident beyond 6 months of treatment."

Adverse events • Journal • Retrospective data • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heart Failure • Heterozygous Familial Hypercholesterolemia • Ischemic stroke • Metabolic Disorders • Myocardial Infarction • APOB

NewAmsterdam Pharma to Participate in Upcoming Medical Meeting and Investor Conferences in September (GlobeNewswire) - "NewAmsterdam Pharma....announced that it will present additional pooled safety and efficacy data from the pivotal Phase 3 BROADWAY and BROOKLYN trials at the European Society of Cardiology Congress (ESC), taking place August 29 – September 1, 2025 in Madrid, Spain."

P3 data • Cardiovascular • Dyslipidemia • Heterozygous Familial Hypercholesterolemia

Obicetrapib and cardiovascular events (ESC-WCC 2025) - No abstract available

Late-breaking abstract • Cardiovascular

Efficacy of obicetrapib across the spectrum of background lipid lowering therapies-pooled analyses of the Broadway and Brooklyn randomised trials (ESC-WCC 2025) - "For this analysis, patients were stratified by binary status (Yes/No) for any statin use, intensity (high, medium/low), ezetimibe, and PCSK9i as well as combination therapy (defined as any two classes of medications). In very-high and high risk patients with ASCVD or HeFH, Obi provided significant additional reductions in LDL-C and other atherogenic lipids across the spectrum of concomitant LLTs. Obicetrapib is a promising therapy as an adjunct to existing LLT for patients whose LDL-C remains uncontrolled."

Clinical • Cardiovascular • Dyslipidemia • APOB

Safety and efficacy of obicetrapib in dyslipidemia: systematic review and meta-analysis (ESC-WCC 2025) - "We conducted a meta-analysis of five randomized controlled trials (n = 452 patients) to evaluate the impact of obicetrapib on lipid parameters assessing both efficacy and safety outcomes. Obicetrapib therapy at 5 mg and 10 mg doses resulted in significant changes in LDL-C [MD: -33.06%; 95% CI: -43.03, -32.28; p<0.00001], HDL-C [MD: 154.92%; 95% CI: 143.35, 166.48; p<0.00001], non-HDL-C [MD: -31.44%; 95% CI: -35.51, -27.36; p<0.00001], Apo E [MD: 40.03%; 95% CI: -29.83, 50.23; p<0.00001], Apo B [MD: -25.86%; 95% CI: -30.60, -21.13; p < 0.00001] and Apo A [MD: 54.32%; 95% CI: 47.87, 60.77; p<0.00001]. Changes in triglycerides [MD: -4.99%; 95% CI: -11.31, 1.34; p=0.12] and VLDL [MD: -5.48%; 95% CI: -13.98, 3.01; p=0.21] were not statistically significant."

Retrospective data • Review • Cardiovascular • Dyslipidemia • APOE

VINCENT: Impact of Obicetrapib and Obicetrapib Plus Repatha on Lp(a) Levels (clinicaltrials.gov) - P2 | N=69 | Recruiting | Sponsor: NewAmsterdam Pharma | N=30 ➔ 69

Enrollment change • Dyslipidemia • Metabolic Disorders

NewAmsterdam Pharma to Present Alzheimer’s Biomarker Data from BROADWAY Trial at AAIC 2025 (The Manila Times) - "NewAmsterdam Pharma...announced that it will present full data from the prespecified Alzheimer’s Disease (AD) biomarker analyses in the BROADWAY clinical trial (NCT05142722) in a late-breaking oral presentation at the Alzheimer’s Association International Conference (AAIC), being held July 30, 2025 in Toronto, Canada....NewAmsterdam will host a live webcast and conference call at 10:00 a.m. ET on July 30, 2025 to review the full AD biomarker data presented at AAIC."

Late-breaking abstract • P3 data • Alzheimer's Disease • Cardiovascular

NewAmsterdam Announces Acceptance of Marketing Authorization Applications for Review by European Medicine Agency for Obicetrapib (GlobeNewswire) - "Filings both for the obicetrapib monotherapy and obicetrapib plus ezetimibe fixed-dose combination submitted to EMA by our partner, Menarini, for treatment of adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia....The EMA submission is based on data from BROOKLYN, TANDEM and BROADWAY Phase 3 trials..."

EMA filing • Dyslipidemia • Familial Hypercholesterolemia • Heterozygous Familial Hypercholesterolemia

NewAmsterdam Pharma Presents Positive Data from BROADWAY Trial Demonstrating Statistically Significant Reductions in Key Alzheimer’s Disease Biomarkers at AAIC 2025 (GlobeNewswire) - P3 | N=2,530 | BROADWAY (NCT05142722) | Sponsor: NewAmsterdam Pharma | "NewAmsterdam...announced full data from the prespecified Alzheimer’s disease ('AD') biomarker analysis in the BROADWAY clinical trial (NCT05142722)...In connection with this trial, a prespecified analysis evaluated the effect of obicetrapib on plasma biomarkers of AD in 1,515 patients with established ASCVD and/or HeFH whose ApoE status was able to be determined, including 367 ApoE4 carriers. Safety in this population was not evaluated independently from the overall BROADWAY study population, where obicetrapib was observed to be well-tolerated, with safety results comparable to placebo....Treatment with obicetrapib 10 mg daily for 12 months resulted in statistically significant lower absolute changes in plasma p-tau217, a key biomarker of AD pathology, in both the analysis set (p=0.0019) and in ApoE4 carriers (p=0.0215)."

P3 data • Alzheimer's Disease • Cardiovascular • Heterozygous Familial Hypercholesterolemia

Obicetrapib and CETP inhibition: An exception to the rule? (PubMed, Med) - "In two phase 3 trials, BROADWAY1 and TANDEM,2 obicetrapib alone or with ezetimibe lowered LDL-C, apolipoprotein B, and Lp(a) levels in patients with high cardiovascular risk. Given previous CETP inhibitor failures, results of the ongoing cardiovascular outcome study are needed to confirm obicetrapib's cardiovascular benefits."

Journal • Cardiovascular • APOB

Obicetrapib and its impact on lipid parameters: A comprehensive meta-analysis of the latest evidence. (PubMed, J Clin Lipidol) - "Obicetrapib significantly improves key lipid parameters, including LDL-C, Apo-B, non-HDL-C, HDL-C, and Lp(a), with enhanced efficacy in lowering LDL-C, Apo-B, and non-HDL-C when combined with ezetimibe. These findings support its potential role in comprehensive lipid management strategies."

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

NewAmsterdam Pharma Provides Corporate Update and Reports Second Quarter Financial Results (GlobeNewswire) - "Upcoming Milestones and Ongoing Trials: Following the successful completion and positive topline results of the Phase 3 BROADWAY, TANDEM, and BROOKLYN trials, NewAmsterdam plans to announce additional data from these trials over the course of 2025 relating to obicetrapib and the fixed-dose combination ('FDC') of obicetrapib plus ezetimibe....R&D expenses were $27.5 million in the quarter ended June 30, 2025, compared to $38.4 million for the same period in 2024. This decrease was primarily due to a decrease in clinical expenses, partially offset by an increase in personnel expenses, including share-based compensation, non-clinical expenses related to pipeline expansion and product lifecycle management, and regulatory expenses primarily driven by the preparation and planned submission of regulatory applications for obicetrapib."

Commercial • P3 data: top line • Alzheimer's Disease • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia

Rationale and design of the REMBRANDT trial: A phase 3 study to evaluate the effect of obicetrapib/ezetimibe on coronary plaque characteristics. (PubMed, Am Heart J) - P3 | "The REMBRANDT trial will determine whether the favorable effects of obicetrapib and ezetimibe FDC on LDL-C translate to a reduction in coronary plaque burden as a potential mechanism for ASCVD risk reduction."

Journal • P3 data • Atherosclerosis • Cardiovascular • Dyslipidemia

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

Weekly Journal Scan: obicetrapib and the revival of cholesteryl ester transfer protein inhibition. (PubMed, Eur Heart J) - No abstract available

Journal

A Drug-Drug Interaction Study Evaluating the Pharmacokinetic Consequences of Obicetrapib Therapy on Atorvastatin or Rosuvastatin Levels in Healthy Volunteers. (PubMed, Am J Cardiovasc Drugs) - P1 | "No clinically significant PK interaction occurred between multiple daily doses of obicetrapib on the single-dose PK of either atorvastatin or rosuvastatin in healthy volunteers."

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

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

† 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