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

Esperion Reaches Settlement Agreement with ANDA Filer Not to Market Generic Version of NEXLETOL (bempedoic acid) Prior to April 19, 2040 (GlobeNewswire) - "Esperion...announced that it has entered into a settlement agreement with Micro Labs USA, Inc. and its affiliate Micro Labs Limited (together, Micro Labs). This agreement resolves the patent litigation brought by Esperion against Micro Labs in response to Micro Labs’ Abbreviated New Drug Application (ANDA) seeking approval to market a generic version of NEXLETOL prior to the expiration of the applicable patents. Pursuant to the agreement, Micro Labs has agreed not to market a generic version of NEXLETOL in the United States prior to April 19, 2040, unless certain limited circumstances customarily included in these types of agreements occur."

Commercial • Cardiovascular

Global Expansion (GlobeNewswire) - "Neopharm Israel filed a New Drug Application for marketing approval of NEXLETOL and NEXLIZET in Q1 2025; The Company’s previously filed New Drug Submissions to Health Canada for NEXLETOL and NEXLIZET are on track for review with an expected market approval in the fourth quarter of 2025."

Canada approval • Filing • Dyslipidemia • Heterozygous Familial Hypercholesterolemia

Hypercholesterolemia and cardiovascular disease: the dilemma of effective treatment for target achievement according to guidelines and national healthcare policies and a call to action. (PubMed, Minerva Cardiol Angiol) - "Statins, ezetimibe, bempedoic acid, pro-protein convertase subtilisin/kexin 9 inhibitors (i.e., the monoclonal antibodies alirocumab and evolocumab, or the small interfering RNA inclisiran) are all available for reaching LDL-C targets according to risk profile. Regular monitoring of the effects of the prescribed therapy, also through e-health and telemedicine tools, is essential, as well as changing therapy when LDL-C is not adequately controlled. Finally, health systems should align with guidelines and promote good clinical practices, overcoming a silo system, to impact outcomes in terms of overall sustainability."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders

Improving Lipid Optimization Quality and Treatment Options in ASCVD (clinicaltrials.gov) - P4 | N=300 | Not yet recruiting | Sponsor: Brigham and Women's Hospital

New P4 trial • Dyslipidemia • Metabolic Disorders

Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis. (PubMed, Proc Natl Acad Sci U S A) - "Treating mice with antisense oligonucleotides against Coenzyme A synthase (Coasy) or treatment with bempedoic acid or atorvastatin decreased liver lipid droplet cholesterol content and prevented CDAHFD-induced MASH and the fibrotic response. Analysis of human liver samples demonstrated that cholesterol in liver lipid droplets was increased in humans with MASH and liver fibrosis and was higher in PNPLA3 I148M (variants rs738409) than in HSD17B13 variants (rs72613567). Together, these data identify cholesterol in liver lipid droplets as a critical mediator of MASH and demonstrate that Coenzyme A synthase knockdown and bempedoic acid are therapeutic approaches to reduce liver lipid droplet cholesterol content and thereby prevent the development of MASH and liver fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • PNPLA3

Prescriber Uptake and Use of Novel Lipid-Lowering Therapies. (PubMed, J Am Heart Assoc) - "The majority of US clinicians prescribing LLT have never prescribed a PCSK9i or BA, and among those who do, most have used these therapies in only a few patients. However, there exist distinct groups of early adopters and high-volume users with higher approval rates, slightly more years in practice, and more cardiologists. Given that prescription approval rates for both PCSK9i and BA have now increased to >80% in our analysis, increasing uptake of novel LLT will require interventions to increase use among clinicians."

Journal • Cardiovascular

Molecular targets of bempedoic acid and related decoy fatty acids. (PubMed, Trends Endocrinol Metab) - "However, BPA treatment also has ACLY-independent effects on lipid metabolism, as the structural similarity of BPA to endogenous fatty acids allows it to trigger multiple lipid-signaling pathways. Here, we review the molecular targets of BPA and related 'decoy fatty acid' drugs and identify areas where further study is warranted as these molecules are evaluated for clinical indications."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Esperion Reports First Quarter 2025 Financial Results (GlobeNewswire) - "Q1 2025 Total Revenue of $65.0 Million, a Decrease of 53% Y/Y; Adjusting for One Time Milestone Received in Q1 2024, Total Revenue Grew 63% Y/Y; Q1 2025 U.S. Net Product Revenue Grew 41% Y/Y to $34.9 Million; Bempedoic Acid Earned Level 1a Recommendations in the 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients with Acute Coronary Syndromes; Esperion’s European partner Daiichi Sankyo Europe (DSE) continues to show strong revenue growth and market penetration for NILEMDO (bempedoic acid) and NUSTENDI (bempedoic acid and ezetimibe), providing increased royalty revenue and underscoring the significant market opportunity for Esperion’s bempedoic acid products worldwide."

Commercial • Dyslipidemia

Esperion Partners with HLS Therapeutics to Commercialize NEXLETOL (bempedoic acid) and NEXLIZET (bempedoic acid and ezetimibe) in Canada (GlobeNewswire) - "Esperion Therapeutics...announced it has entered into a license and distribution agreement with HLS Therapeutics...for the exclusive rights to commercialize NEXLETOL and NEXLIZET in Canada. Under the terms of the agreement, Esperion will receive an upfront payment, near-term milestone and tiered royalties on product sales. Esperion will be responsible for supplying finished product to HLS Therapeutics at a profitable transfer price...Under the terms of the license and distribution agreement, Esperion will grant HLS Therapeutics exclusive commercialization rights to NEXLETOL and NEXLIZET in Canada. HLS Therapeutics will be responsible for commercialization, including reimbursement and marketing....Esperion will receive an upfront payment and be eligible for milestone payments of up to approximately $5 million along with tiered royalties on product sales."

Licensing / partnership • Cardiovascular

Modelling Methods for Economic Evaluations of Non-Statin Lipid Lowering Therapies for Reducing Cardiovascular Risk: A Systematic Literature Review (ISPOR 2025) - "Included studies evaluated the cost-effectiveness of alirocumab, evolocumab, ezetimibe, bempedoic acid, and inclisiran, with varying outcomes and conclusions reported across studies. This SLR identified various decision analytical models for evaluating non-statin LLTs for managing LDL-C and CV risk, with the Markov cohort model as the most commonly employed method. Despite variations in inputs and representations of health states, the economic models shared structural similarities. These findings provide guidance for the lipid and payer community, and provide valuable insights for future research and economic model development in the CV field."

HEOR • Review • Cardiovascular

In vivo effects of bempedoic acid on microdosed CYP probe drugs. (PubMed, Front Pharmacol) - "The outcome measures were as follows: 1) the omeprazole AUC0-4h and hydroxylation index (HI) after a 100 µg dose to evaluate CYP2C19 activity, 2) the midazolam AUC2-4h after a 30 µg dose to evaluate CYP3A activity, and 3) the yohimbine AUC0-4h after a 50 µg dose to evaluate CYP2D6 activity. There was no change in the AUC2-4h of midazolam (GMR: 1.18, 90% CI: 0.87-1.61) and AUC0-4h of yohimbine (GMR: 0.92, 90% CI: 0.75-1.14). In healthy volunteers, BA was a mild inducer of CYP2C19 and did not affect CYP3A or CYP2D6 activity."

Journal • Preclinical • CYP2C19

Access to Bempedoic Acid - A Real World Assessment in an Academic Clinical Practice (ENDO 2025) - "The most common reasons for denial or lack of initiation of BA were 1) the need for a trial of either ezetimibe or PCSK-9 inhibitor, 2) substantial co-pay, or 3) conditional approval for a year. Our real-world study confirms that BA is effective in achieving a significant reduction in LDL-C levels for up to a year and minimal side effects, similar to the previous efficacy studies. However, significant challenges due to insurance coverage remain, such as need for use of other LDL-C lowering agents and high co-pays that continue to limit patients' access to this medication.*. .*"

Clinical • Real-world • Real-world evidence • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Metabolic Disorders • Musculoskeletal Pain • Pain • Type 2 Diabetes Mellitus

Sexual dimorphism of Sprague-Dawley rats in the liver inflammatory/fibrotic response to a high in sucrose and fat, choline-deficient, L-amino acid CDAA diet (EASL 2025) - "Background and Aims: We have shown the efficacy and security of bempedoic acid and pemafibrate in an experimental model of simple metabolic dysfunction-associated steatotic liver in Sprague-Dawley (SD) rat (Biomedicines 10 (2022) 1517, Biomed&Pharmacother 177 (2024) 117067). There is a clear sexual dimorphism in the response of SD rats to a CDAA diet, with males developing MASH after three months of continuous CDAA diet supplementation, while females not showing any clear increase in liver fibrotic markers after five months of CCDA diet supplementation."

Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Oncology • ACTA2 • COL1A1 • GDF15 • IL1B • IL6 • TGFB1 • TIMP1 • TNFA

Inadequate Response to PCSK9 Inhibitors. (PubMed, JACC Case Rep) - "A higher rate of suboptimal PCSK9i responses have been reported in real-world data than in randomized clinical trials (7.5% vs 1%), warranting further investigation to understand mechanisms. The use of combination therapy based on individual response and tolerance is essential to assure goal attainment and improve residual risk in patients with suboptimal response."

Clinical • Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Metabolic Disorders • Pain

Effectiveness of proprotein convertase subtilisin/kexin type 9 inhibitors in managing hypercholesterolemia post-statin-associated immune-mediated necrotizing myopathy: report of five cases and literature review. (PubMed, Rheumatol Int) - "All patients were treated with steroids (with a gradual dosage reduction), and four of the five received second line immunosuppressive therapy, such as intravenous immunoglobulin, methotrexate, azathioprine, and mycophenolate mofetil...Additionally, ezetimibe and bempedoic acid were used successfully in some patients. Finally, lipid levels appeared to be lower after treatment with PCSK9 inhibitors. Administration of PCSK9 inhibitors appears to be an effective and safe option for the treatment of dyslipidaemia in patients with IMNM."

Journal • Review • Dyslipidemia • Immunology • Metabolic Disorders • Myositis

Single Dose Oral Bioequivalence Study of Bempedoic Acid 180 mg Film Coated Tablet and Nilemdo® (Bempedoic Acid) 180 mg Film-coated Tablets in Healthy Adult Human Subjects Under Fasting Conditions. (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Humanis Saglık Anonim Sirketi

New P1 trial • Cardiovascular • Dyslipidemia • Mixed Hyperlipidemia

CLEAR Taiwan: A Multicenter, Prospective, Phase IV, Interventional 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 | Not yet recruiting | Sponsor: Daiichi Sankyo Taiwan Ltd.

New P4 trial • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia • APOB

Consumption and expenditure of drugs used for the treatment of hypercholesterolemia: a governance analysis. (PubMed, Expert Rev Pharmacoecon Outcomes Res) - "While statins have long been the cornerstone for lowering LDL cholesterol, their associated side effects have prompted the exploration of alternative treatments, including ezetimibe, bempedoic acid, PCSK9 inhibitors and inclisiran. The landscape of hypercholesterolemia treatment has expanded with several new therapeutic options. Bempedoic acid may mitigate adverse effects and enhance treatment efficacy, potentially delaying the need for costlier injectable medications like evolocumab, alirocumab, and inclisiran."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders

Protective potential of bempedoic acid as an AMPK activator in tamoxifen-induced steatohepatitis in rats. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Mechanistically, BA significantly decreased oxidative stress by decreasing the level of malondialdehyde (MDA) and increasing the level of superoxide dismutase (SOD), significantly reduced inflammatory cytokines such as nuclear factor-kappa B (NF-κB/p65) and tumor necrosis factor-alpha (TNF-α), significantly inhibited lipogenesis by decreasing sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthetase (FAS), acetyl-coenzyme A carboxylases (ACC), ATP-citrate lyase (ACL), and significantly promoted fatty acid oxidation be enhancing carnitine palmitoyl transferase 1 significantly (CPT-1) through AMP-activated protein kinase (AMPK) activation. These findings suggest BA as a potential adjunct therapy for TAMX-induced metabolic dysfunction-associated steatohepatitis (MASH)."

Journal • Preclinical • Dyslipidemia • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • TNFA

A Long-term Trial of ETC-1002 in Patients With Hyper-LDL Cholesterolemia (clinicaltrials.gov) - P3 | N=130 | Completed | Sponsor: Otsuka Pharmaceutical Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia

IMPACT OF ADJUNCTIVE LIPID-MODIFYING THERAPY IN THE CLEAR OUTCOMES TRIAL - Venu Menon (ACC 2025) - "Background: Randomization of statin intolerant patients to bempedoic acid (BA) resulted in a 13% reduction in the risk of MACE4 (CV death, nonfatal myocardial infarction, nonfatal stroke or coronary revascularization) compared to placebo (PBO) in the Clear Outcomes trial (n= 13,970)... A minority of patients in Clear Outcomes (PBO > BA) were treated with LMT during the trial. The timing of LMT initiation in > 90% of subjects occurred after the observed first MACE event. Consequently, censored data at LMT initiation shows negligible impact of LMT cross-in on the overall primary endpoint."

Cardiovascular • Myocardial Infarction

EFFICACY AND SAFETY OF BEMPEDOIC ACID FOR LDL-C REDUCTION IN STATIN-INTOLERANT PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS - Muhammad Adil Afzal (ACC 2025) - "BA shows promise in lowering cholesterol in statin-intolerant patients, mainly due to its favorable muscle-related side effect profile. However, larger RCTs focusing on diverse populations must further ascertain BA's efficacy and safety."

Retrospective data • Review • Cardiovascular • Renal Disease • APOB

RESDIUAL ATHEROGENIC RISK: LDL PARTICLE NUMBER PREDICITS CARDIAC EVENTS DESPITE THERAPEUTIC LDL-C - Alexis Parks (ACC 2025) - "Background: While total LDL-C is a predominant predictor of atherosclerosis and is the main target for therapy, other lipoproteins, notably non-HDL cholesterol, Apolipoprotein B, and LDL particle number (LDL-P) are additional markers of residual risk.Case: 60 year old male with family history of early coronary disease and atherogenic dyslipidemia has LDL of 147 mg/dL & elevated LDL-P of 1,763 nmol/L and small LDL-P of 1,037 nmol/dL at baseline (Fig C); he is placed on atorvastatin 10 mg daily for many years with satisfactory LDL-C response. LDL-P and small LDL-P can provide further information on residual risk not traditionally addressed by LDL-C, favoring more intensive lipid lowering."

Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • Myocardial Infarction • Pain • APOB • CRP

EVALUATING THE IMPACT OF LDL-C REDUCTION ON RECURRENT MI AND STROKE RELATED HOSPITALIZATIONS USING CAUSAL MACHINE LEARNING IN A REAL WORLD DATA - Fang He (ACC 2025) - "The causal models were developed to predict the impact of LDL-C reduction on MI-/stroke-related hospitalization, adjusted for patient demographics, comorbidities, types of the index ASCVD event, and lipid-lowering therapies (LLTs, i.e., statin, ezetimibe, PCSK9i, bempedoic acid) at baseline and during follow-up. The final cohort included 85,253 patients (mean age 62.4 years, 48.4% males, median LDL-C 94 [Q1, Q3: 72, 121] mg/dL, 41.8% not receiving any LLTs at baseline) with median follow-up of 3.7 years; among which 6.8% patients experienced MI-/stroke-related hospitalization within one year following the initial ASCVD event. Our findings suggested a clear benefit of LDL-C reduction in preventing MI- or stroke-related hospitalizations among secondary prevention patients."

Clinical • Machine learning • Real-world • Real-world evidence • Cardiovascular

WHEN TO BRING OUT THE HEAVY ARTILLERY : MANAGING RESISTANT FAMILIAL HYPERCHOLESTERMIA (FH) WITH BEMPEDOIC ACID - Victor Adenuga (ACC 2025) - "clinicians should be familiar with newer alternatives in lipid lower therapy. In patients who have shown intolerance to first line therapies, newer alternatives should be considered."

Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • Musculoskeletal Pain • Pain