Nexletol (bempedoic acid) / Esperion Therap, Otsuka, Daiichi Sankyo, NeoPharm, HLS Therap, CSL Behring - LARVOL DELTA

Structure-guided discovery of potent acly inhibitors with therapeutic potential in ALK+ anaplastic large cell lymphoma and other hematologic malignancies (ASH 2025) - "The recent FDA approval of Bempedoic Acid (ETC-1002) for hypercholesterolemia clinically validates ACLY as a druggable target... Our structure-guided virtual screening approach led to the discovery of novel, cell-permeable ACLY inhibitors with potent enzymatic and cellular activity in ALK+ ALCL and other hematologic malignancies. These compounds overcome limitations of existing ACLY inhibitors and hold promise as a new class of metabolic therapeutics targeting ACLY systemically in blood cancers. Further preclinical development is warranted."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Dyslipidemia • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ACLY • SLC27A2

Emerging Therapies in Autosomal Dominant Polycystic Kidney Disease. (PubMed, Kidney360) - "Tolvaptan, a vasopressin V2 receptor antagonist, established cAMP modulation as a disease-modifying strategy but is limited by aquaretic effects and hepatotoxicity risk...Gene-directed therapies aim to restore polycystin dosage, including anti-miR-17 oligonucleotides (e.g., farabursen) and pharmacochaperones that rescue misfolded PC1 and restore trafficking in select PKD1 missense variants (e.g., VX-407)...Metabolic reprogramming is targeted by agents such as metformin, bempedoic acid, GLP-1 receptor agonists, and structured dietary interventions...Collectively, these advances signal a transition toward a layered, mechanism-guided framework in which vasopressin blockade is integrated with metabolic, other signaling, and genotype-specific therapies. As biomarkers and risk stratification tools mature, ADPKD management is poised to become increasingly precise, tolerable, and effective."

Journal • Autosomal Dominant Polycystic Kidney Disease • Gene Therapies • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease • IGF1 • MIR17 • PKD1 • PRKD1

Clinical Response to Elevated Lipoprotein(a): Practical Approach for Risk Management in the Absence of Targeted Therapies. (PubMed, Semin Thromb Hemost) - "Statins, ezetimibe, bempedoic acid and lifestyle interventions have little or no effect on Lp(a). Statins may modestly raise levels, niacin is now contraindicated as it has not been shown to reduce cardiovascular or all-cause mortality, while PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors and inclisiran reduce Lp(a) concentrations by ~20-30%, though this effect remains secondary to their LDL-C lowering effect...Future promise lies in RNA-based therapies, including antisense oligonucleotides (pelacarsen) and small-interfering RNAs (olpasiran, lepodisiran, SLN360), which achieve 80-95% sustained Lp(a) reductions...High or extreme elevations, especially with ASCVD, mandate aggressive LDL-C lowering, optimization of modifiable risk factors, family cascade screening, and apheresis or referral to RNA-therapy trials in select cases. Thus, while therapeutic options remain limited, systematic measurement and risk stratification are ethically justified to prepare..."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

CLEAR Taiwan: A Study to Investigate the Effectiveness and Safety of Bempedoic Acid in Patients With Primary Hypercholesterolemia or Mixed Dyslipidemia in Taiwan (clinicaltrials.gov) - P4 | N=180 | Completed | Sponsor: Daiichi Sankyo | Recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia • APOB

Indications of Bempedoic Acid. (PubMed, Cardiol Rev) - "Randomized controlled trials demonstrate LDL-C reductions of 15-20% with monotherapy and up to 40% with ezetimibe combination, alongside cardiovascular event reduction in statin-intolerant patients. Regulatory approvals in the United States, European Union, and United Kingdom converge on its role in patients unable to tolerate statins or inadequately controlled on standard therapy. This review synthesizes current evidence and guideline positioning, situating bempedoic acid within contemporary lipid management strategies that emphasize earlier combination therapy, achievement of lower LDL-C thresholds, and long-term maintenance of treatment goals."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

COAST Study - Cholesterol Optimization After Stroke (clinicaltrials.gov) - P=N/A | N=500 | Not yet recruiting | Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

New trial • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders

Long-term Safety and Efficacy of Bempedoic Acid in Japanese Patients with Hypercholesterolemia: the CLEAR-J LONG. (PubMed, J Atheroscler Thromb) - "Bempedoic acid 180 mg/day for 52 weeks was well tolerated in patients with hypercholesterolemia, with no major safety concerns. Serious AEs were infrequent, and no new safety signals specific to the Japanese population were observed. More than 60% of patients achieved and sustained their LDL-C target levels."

Journal • Dyslipidemia • Metabolic Disorders • APOB • CRP

AACE Updates Guidelines for Pharmacologic Management of Dyslipidemia in Adults (Endocrinology Advisor) - "Among adults with dyslipidemia receiving treatment with statins who have ASCVD or are at increased risk for ASCVD and have less than 70 mg/dL of low-density cholesterol (LDL-C), evolocumab or alirocumab may be added to standard care; Among adults with dyslipidemia without ASCVD, the task force recommended against the use of evolocumab or alirocumab along with standard care; Among adults with dyslipidemia with statin intolerance who have ASCVD or are at increased risk for ASCVD, the use of bempedoic acid may be considered in addition to standard care."

Clinical guideline • Cardiovascular • Dyslipidemia

Cardiovascular Therapeutics at the Crossroads: Pharmacological, Genetic, and Digital Frontiers. (PubMed, Pharmaceuticals (Basel)) - "Key advances include next-generation lipid-lowering agents such as PCSK9 inhibitors, inclisiran, and bempedoic acid, as well as metabolic drugs like SGLT2 inhibitors, GLP-1 receptor agonists, and dual GIP/GLP-1 agonists, which offer cardiovascular and renal benefits beyond glucose control. In parallel, digital innovations, including artificial intelligence, remote monitoring, and telehealth platforms, are transforming care delivery by enhancing adherence, enabling earlier intervention, and refining risk stratification. Collectively, these developments signify a paradigm shift toward a more personalized, proactive, and systems-based model of cardiovascular care."

Journal • Review • Cardiovascular • Gene Therapies

Relative Efficacy of Alirocumab, Evolocumab, Inclisiran, and Bempedoic Acid on Lipids in Patients with Cardiovascular Disease or Familial Hypercholesterolaemia. (PubMed, J Clin Med) - "Methods and This observational study evaluated the impact of novel lipid-lowering therapies (alirocumab, evolocumab, inclisiran, and bempedoic acid) in patients with a history of atherosclerotic cardiovascular disease or familial hypercholesterolaemia treated with maximum-tolerated doses of high-intensity statin therapy with or without ezetimibe. Strength and limitations: This was the first study to comprehensively compare the efficacy of novel lipid-lowering therapies in achieving guideline-recommended LDL targets within a high-risk cardiovascular population. The sample size was relatively small, especially for patients treated with bempedoic acid."

Journal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia

HLS Therapeutics Announces Health Canada Approval of NILEMDO for the Reduction of LDL-Cholesterol in Canadians at Risk of Cardiovascular Disease (PRNewswire) - "The approval is supported by data from the CLEAR Outcomes trial...NILEMDO will be added to Health Canada's Register of Innovative Drugs and will benefit from eight years of data protection starting from its November 17, 2025, approval. This period, combined with existing and pending patents, provides market exclusivity for the drug extending until 2040....'We are excited to launch NILEMDO in Canada in the second quarter of 2026.'"

Canada approval • Launch Canada • Patent expiry • Cardiovascular

Lipid-Lowering Therapy Is Underutilized Across LDL-C Levels in Autoimmune Disease Compared to Diabetes: A Nationwide Analysis (AHA 2025) - "Statins included atorvastatin, rosuvastatin, simvastatin, pravastatin, lovastatin, fluvastatin, pitavastatin. Non-statin therapies included icosapent ethyl, colesevelam, alirocumab, evolocumab, Bempedoic acid, cholestyramine, Inclisiran, colestipol, ezetimibe, gemfibrozil, omega-3 acid, fenofibrate...Non-statin lipid-lowering therapy use was significantly lower in autoimmune patients compared to those with diabetes across all LDL-C tertiles, with the largest differences observed at LDL <70 mg/dL (6.19% vs 10.24%, p<0.0001) and 70–99 mg/dL (4.05% vs 7.06%, p<0.0001).ConclusionDespite comparable ASCVD risk, patients with autoimmune disease are significantly less likely to receive statins or non-statin lipid-lowering therapy than those with DM across LDL-C levels. These findings show a need for improved cardiovascular prevention in this high-risk population."

Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Hepatology • Immunology • Inflammatory Arthritis • Lupus • Metabolic Disorders • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

Inclisiran Nonresponse with PCSK9 Variant and Successful LDL-C Lowering with Evinacumab in a Patient with Homozygous Familial Hypercholesterolemia (AHA 2025) - "Despite adherence to maximum doses of LLT (Rosuvastatin, Ezetimibe, Bempedoic acid, Alirocumab) and aggressive lifestyle modifications (12lbs weight loss and a vegan diet), he did not reach target LDL <55mg/dL. Evinacumab works by facilitating clearance of lipoproteins via lipoprotein lipase and endothelial lipase and is independent of LDLR/PCSK9 pathway. This case highlights the importance of recognizing limitations in existing lipid-lowering strategies and the need for personalized treatment."

Clinical • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • ANGPTL3 • APOB • LDLR • LPL

CT.MDP.24: Closing the LDL Gap: Innovations, Access, and Adherence in Lipid-Lowering Therapy (AHA 2025) - "Discover the real-world impact of evolocumab, cost and utilization trends in under-treated populations, and access inequities driven by socioeconomic deprivation. With new evidence on emerging agents like bempedoic acid, obicetrapib, and zodasiran, this session brings together cutting-edge science and pragmatic solutions to confront one of cardiology's most persistent challenges: getting LDL down and keeping it there. This is not a CE accredited session."

Adherence • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders

MILOS: Treatment With Bempedoic Acid and/or Its Fixed-dose Combination With Ezetimibe in Primary Hypercholesterolemia or Mixed Dyslipidemia (clinicaltrials.gov) - P=N/A | N=5000 | Active, not recruiting | Sponsor: Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company | Trial completion date: Sep 2025 ➔ Oct 2026 | Trial primary completion date: Sep 2025 ➔ Oct 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia

Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies. (PubMed, Endocrinol Metab (Seoul)) - "While 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, commonly known as statins, as well as ezetimibe, fibrates, and omega-3 fatty acids have established roles in lipid lowering, significant residual risk persists in many patients due to insufficient low-density lipoprotein cholesterol (LDL-C) reduction, elevated triglyceride-rich lipoproteins, and genetically determined elevations of lipoprotein(a) (Lp(a)). Clinical outcome trials have validated bempedoic acid, PCSK9 inhibitors, and icosapent ethyl, while large-scale programs are ongoing for obicetrapib, oral PCSK9 inhibitors, Lp(a)-targeted oligonucleotides, and ANGPTL3-directed RNA therapeutics. This review summarizes the mechanisms, pivotal trials, and clinical implications of innovative lipid-lowering therapies, highlighting how they may reshape future treatment algorithms for ASCVD prevention."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • ANGPTL3 • APOB

Real-world evaluation of bempedoic acid use in patients with homozygous familial hypercholesterolemia. (PubMed, J Clin Lipidol) - "Bempedoic acid in patients with HoFH was both effective for LDL-C lowering and tolerable in this cohort of patients. This represents a novel treatment approach in a very high-risk patient population requiring multi-drug regimen for lipid optimization and cardiovascular protection."

HEOR • Journal • Real-world evidence • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

BASIS: Bempedoic Acid Versus Statins in Primary-Prevention Patients With Suboptimal Statin Adherence: Effects on LDL-C Reduction and Tolerability (clinicaltrials.gov) - P3 | N=690 | Not yet recruiting | Sponsor: Sohaib Ashraf

New P3 trial • Cardiovascular

Acid mitigates BCG-induced depression in mice by modulating TNF-α/NF-κB signaling and restoring brain serotonin contents. (PubMed, Brain Res) - "While ATP-citrate lyase (ACLY) is a key lipogenic enzyme that amplifies immune cell-mediated inflammatory responses, bempedoic acid (BA), a recently approved ACLY inhibitor for hypercholesterolemia, has demonstrated significant anti-inflammatory properties...BA was administered alone or with TNF-α inhibitor etanercept (ET)...This study provides the first evidence of the antidepressant effect of BA, demonstrating that its suppression of peripheral TNF-α leads to downregulation of central NF-κB and restoration of serotonin levels. Further investigations in diverse animal models are warranted to confirm the broad-spectrum efficacy of BA, along with the evaluation of its translational potential for treating depression."

Journal • Preclinical • CNS Disorders • Depression • Dyslipidemia • Major Depressive Disorder • Metabolic Disorders • Mood Disorders • Oncology • Psychiatry • TNFA

A Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 With Ezetimibe Combinations in Healthy Adults With Elevated LDL-C. (clinicaltrials.gov) - P1 | N=81 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders • APOB

Simulation of the Impact on LDLC Targets and Treatment Cost in High and Very High Cardiovascular Risk Patients of Cost-Based Sequencing of Lipid-Lowering Therapy (ISPOR-EU 2025) - "OBJECTIVES: To evaluate the clinical and economic impact of lipid-lowering treatment escalation algorithms including bempedoic acid (BA) in high or very high cardiovascular risk patients not achieving LDL-C targets in Spain. A Monte Carlo simulation was applied to real-world data from Spanish adults with high or very high cardiovascular risk and uncontrolled LDL-C despite at least 4 weeks of statin treatment with or without ezetimibe (EZE). Patients without LDL-C results, already on BA, PCSK9i (alirocumab or evolocumab) or inclisiran (INC), or who had achieved LDL-C targets were excluded... In patients with high or very high cardiovascular risk not controlled with statins and EZE, early inclusion of BA in treatment algorithms can achieve a similar share of patients with controlled LDL-C levels as PSK9 therapy, while significantly reducing budget impact. Cost-based sequencing provides an efficient approach for healthcare systems."

Clinical • Treatment costs • Cardiovascular

Budget Impact Analysis of Inclisiran for the Management of Patients With Atherosclerotic Cardiovascular Disease in India: A Multipayer Analysis (ISPOR-EU 2025) - "The analysis compared scenerios: a) with and b) without Inclisiran + standard of care (SoC) against existing market :SoC alone (includes high dose statins); evolocumab+SoC; bempedoic acid+SoC; ezetimibe+SoC and bempedoic acid+SoC+ezetimibe. The BIA indicates that transitioning to Inclisiran has improved outcomes by reducing MACE+ events and associated costs, thereby alleviating the financial burden for payers."

Clinical • HEOR • Atherosclerosis • Cardiovascular • Dyslipidemia

Care Now, Pay Later (CNPL): Evaluating the Budgetary and Access Implications of a Novel Financing Model for Inclisiran in Atherosclerotic Cardiovascular Disease (ASCVD) Patients in India (ISPOR-EU 2025) - "This analysis compares Inclisiran + standard of care (SoC) against existing market for lipid lowering therapies which includes a) SoC (comprising high dose statins), b) evolocumab+SoC; c) bempedoic acid (BPA)+ SoC; d) ezetimibe+SoC; and e) BPA+ezetimibe+SoC for one year. For LMIC, CNPL demonstrates a potential way for innovator therapies to reduce budgetary impact for the healthcare system. By distributing payments over a period, such schemes can improve budget management and accelerate patient access."

Clinical • Atherosclerosis • Cardiovascular • Ischemic stroke • Myocardial Infarction

A Cost per Responder Analysis of Lipid-Lowering Therapies in Patients With Established Atherosclerotic Cardiovascular Disease in Italy (ISPOR-EU 2025) - "OBJECTIVES: To assess the value of lipid lowering therapies (LLTs) in reaching low-density lipoprotein cholesterol (LDL-C) targets recommended by 2019 EAS/ESC guidelines, we performed a cost per responder analysis in patients with atherosclerotic cardiovascular disease (ASCVD) and uncontrolled hypercholesterolemia after statin therapy (an eligibility criterion for LLT per the Italian National Health system). A microsimulation analysis was performed to estimate the treatment costs per responder, defined as patient reaching LDL-C targets <40 mg/dL and <55 mg/dL with LLT (alirocumab, bempedoic acid±ezetimibe, evolocumab, and inclisiran) available in Italy. Among LLTs available in Italy, evolocumab reported the highest value with the lowest cost per ASCVD patient effectively treated. This analysis can help decision makers identify the most cost-effective treatment to reach the desired clinical outcome."

Clinical • HEOR • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

Repurposing bempedoic acid as a therapeutic option in GSD type 1: from biochemical principles to first clinical data (SSIEM 2023) - "Based on a reduction in malonyl-CoA levels, BA can improve metabolic control in GSD1. In a pilot study, BA had a positive effect on metabolic control in patients with GSD1 without side effects. Therefore, repurposing of BA may be a novel treatment option in patients suffering from GSD1."

Clinical data • Dyslipidemia • Hypoglycemia • Metabolic Disorders • SLC27A2