Praluent (alirocumab) / Sanofi, Regeneron - LARVOL DELTA

Effectiveness of PCSK9 inhibitors versus statins in type 2 diabetes and dyslipidemia: a propensity-matched study. (PubMed, Front Endocrinol (Lausanne)) - "The association was significant for alirocumab and evolocumab, but not for inclisiran, likely due to limited sample size. Among patients with T2D and dyslipidemia, PCSK9i use was associated with reduced incidences of cardiovascular and renal events and all-cause mortality compared to statin therapy. These findings support the promising role of PCSK9is in high-risk diabetic populations."

Clinical • Journal • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Cost-utility analysis of PCSK9 inhibitors for hypercholesterolemia: a Chinese healthcare perspective. (PubMed, Front Pharmacol) - "In the base-case analysis, evolocumab 140 mg every 2 weeks (Q2W) was the most cost-effective option, dominating all other active regimens...All other regimens were dominated, and inclisiran showed the least favorable cost-utility profile (ICUR $113,800.14 per QALY)...Alirocumab 75 mg Q2W and tafolecimab 150 mg Q2W also represent cost-effective alternatives. These findings provide important evidence to support clinical decision-making and optimize resource allocation in China."

HEOR • Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders

Oxidized Phospholipids, Lipoprotein(a), and Cardiovascular Outcomes after Acute Coronary Syndrome. (PubMed, Circulation) - P3 | "OxPL-apoB levels and Lp(a) were measured in 11 630 participants before and 5185 participants 4 months after randomization to alirocumab or placebo in the ODYSSEY OUTCOMES trial...The interaction of OxPL-apoB and Lp(a) in the placebo group indicates that OxPL-apoB independently predicts MACEs when Lp(a) levels are relatively low. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT001747 and NCT01663402."

Journal • Acute Coronary Syndrome • Cardiovascular • APOB

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

Effect of alirocumab on coronary plaque stratified by atherothrombotic risk. (PubMed, Atherosclerosis) - "Among AMI patients, the addition of alirocumab to high-intensity statin therapy resulted in greater coronary plaque regression and lipid burden reduction in patients not at VHR. Further investigation is needed to clarify the impact of atherothrombotic risks on plaque regression and subsequent risk reduction in different patient subsets."

Clinical • Journal • Atherosclerosis • Cardiovascular • Myocardial Infarction

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

Efficacy and safety of alirocumab in patients with established atherosclerotic vascular disease before the first cardiovascular event: Pooled analysis of phase 3 ODYSSEY studies. (PubMed, J Clin Lipidol) - "Among patients with ASCVD without previous ACS or stroke, alirocumab significantly reduced calculated LDL-C levels vs controls and was well tolerated."

Journal • P3 data • Retrospective data • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Metabolic Disorders • Myocardial Infarction

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

Predicting human subcutaneous bioavailability of monoclonal antibodies using an open flow microperfusion porcine model. (PubMed, J Control Release) - "This study presents a novel approach combining open flow microperfusion (OFM) technology in a porcine model with physiologically based pharmacokinetic (PBPK) modeling to investigate local mAb-tissue interactions and predict human bioavailability of three commercially available mAbs (alirocumab, brodalumab, secukinumab). Furthermore, tissue biopsies indicated an inverse correlation between local mAb retention and human SC bioavailability. Our integrated approach of OFM technology and OFM-informed PBPK modeling thus offers a robust strategy for predicting human SC bioavailability of mAbs."

Journal • Preclinical

Fair pricing, fair access; a systematic review of cost-effectiveness of new hyperlipidemia injectable medication in developing countries. (PubMed, Cost Eff Resour Alloc) - "Cost-effectiveness of PCSK9 inhibitors and inclisiran varies across developing countries, driven by drug prices, WTP thresholds, and healthcare perspectives. Evolocumab may be cost-effective in high-risk subgroups or in Mexico and Saudi Arabia but remains largely unaffordable elsewhere. Ezetimibe was consistently more favorable. Price reductions, tiered pricing, pooled procurement, and context-specific thresholds are essential to improve access and equity."

HEOR • Journal • Pricing • Review • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • Myocardial Infarction

Breakthrough LDL-C reduction in a patient with autosomal recessive homozygous familial hypercholesterolemia: Efficacy of evinacumab after LDL-apheresis discontinuation. (PubMed, J Clin Lipidol) - "The introduction of evinacumab, an LDL receptor-independent lipid-lowering therapy, achieved robust and sustained LDL-C reduction, while eliminating the need for LDL-apheresis and reducing the indirect logistical burden of frequent hospital-based treatments in this patient with AR-HoFH."

Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hematological Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Myocardial Infarction

A disproportionality analysis on proprotein convertase subtilisin/kexin type 9 inhibitors and hypersensitivity and anaphylaxis. (PubMed, Sci Rep) - "We calculated reporting odds ratios (ROR), proportional reporting ratios, and information components (IC) as measures of disproportionate reporting of hypersensitivity or anaphylaxis with PCSK9 inhibitors overall and with specific compounds (alirocumab, evolocumab) using the entire FAERS as comparator. Our large pharmacovigilance study showed no signal of disproportionate reporting for hypersensitivity or anaphylaxis with PCSK9 inhibitors overall. The inconsistencies in alirocumab related findings argue against a compound specific signal."

Journal • Immunology

PCSK9 Inhibition Protects Against Myocardial Ischemia-Reperfusion Injury in Type 2 Diabetes Rats Via Suppressing Inflammation and Apoptosis. (PubMed, Anatol J Cardiol) - "Alirocumab and atorvastatin effectively attenuated myocardial I/R injury in T2DM by modulating lipid metabolism, inflammation, and apoptosis. Diabetes substantially intensified I/R-induced cardiac injury, underscoring the importance of metabolic control in cardioprotection. #Means they contributed equally to the article."

Journal • Preclinical • Cardiovascular • Diabetes • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Myocardial Ischemia • Oncology • Reperfusion Injury • Type 2 Diabetes Mellitus • CASP3 • IL1B • IL6 • NLRC5 • NLRP3 • PCSK9

Cardiac Allograft Vasculopathy Inhibition with AliRocumab: The CAVIAR Trial (AHA 2025) - "The multicenter, randomized, double-blind CAVIAR trial is expected to provide valuable data regarding the safety and efficacy of PCSK9 inhibition early after heart transplantation. By incorporating comprehensive assessments of coronary physiology and plaque composition, this trial may offer crucial mechanistic insights into the benefits of aggressive lipid-lowering therapy in transplant recipients."

Late-breaking abstract • Cardiovascular • Dyslipidemia • Metabolic Disorders

Alirocumab therapy effectively suppresses colorectal cancer cell Growth and invasion in nude mouse liver-PCSK9 is a key driver of PI3K/Akt/p-Bad-mediated cell proliferation and antiapoptotic signaling. (PubMed, Int J Surg) - "Alirocumab-facilitated 5-FU therapy effectively suppresses PCSK9-promoted CRC proliferation/growth/invasion, highlighting that alirocumab therapy may be an alternative choice of adjuvant therapy in combination with surgery or chemotherapy."

Journal • Preclinical • Colorectal Cancer • Oncology • Solid Tumor • DLD • PCSK9

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

Impact of Inclusion of Drug Adherence on Cost-Effectiveness of Inclisiran in Atherosclerotic Cardiovascular Disease (ASCVD) Patients (ISPOR-EU 2025) - "Inclisiran achieved improved cost-effectiveness estimates against both PCSK9is when adherence was included in the model. These findings underscore the importance of incorporating adherence into health economic evaluations to better inform payer decision-making."

Adherence • Clinical • Cost effectiveness • Drug adherence • HEOR • Atherosclerosis • Cardiovascular

Impact of Pharmacotherapy Adherence on the Reduction of Major Adverse Cardiovascular Events (MACE) Among Atherosclerotic Cardiovascular Disease (ASCVD) Patients (ISPOR-EU 2025) - "(2016), and by adjusting the effect sizes reported in the network meta-analysis (60.01% for inclisiran, 58.08% for alirocumab, and 62.01% for evolocumab) in proportion to adherence levels. When adjusting clinical trial data to adherence levels, the LDL-C lowering potential of inclisiran and PCSK9is changes. As more patients are adherent to inclisiran compared to PCSK9is, inclisiran has a higher adherence-adjusted LDL-C lowering effect, resulting in fewer events in inclisiran treated patients. This analysis highlights the substantial impact of real-world adherence on clinical outcomes in ASCVD patients treated with lipid-lowering therapies."

Adherence • Adverse events • Clinical • Atherosclerosis • Cardiovascular

Comparative Efficacy of Ongericimab Versus Six PCSK9 Inhibitors in Treating Hypercholesterolemia or Mixed Dyslipidemia: A Network Meta-Analysis (ISPOR-EU 2025) - "This study aimed to assess the relative lipid-lowering efficacy of ongericimab compared with other PCSK9 inhibitors through a network meta-analysis (NMA). We conducted a systematic literature review (SLR) to identify phase 3 randomized controlled trials (RCTs) of ongericimab and six other PCSK9 inhibitors (evolocumab, alirocumab, tafolecimab, recaticimab, ebronucimab, and inclisiran) assessing efficacy in adult patients with hypercholesterolemia or mixed dyslipidemia, compared with background lipid-lowering therapies. Ongericimab demonstrated superior efficacy in reducing LDL-C and Lp(a) levels compared with most existing PCSK9 inhibitors. These findings may inform clinical decisions and support formulary positioning in lipid-lowering treatment strategies."

Retrospective data • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia

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

Comparison of Nonstatin Lipid-Lowering Therapies (LLTs) by Their Annual Cost per Effectively Treated Very High-Risk Patient in Spain (ISPOR-EU 2025) - "Compared to other LLTs used in the secondary prevention setting, adding evolocumab 140 mg Q2W to background statins resulted in the highest proportion (80%) of very high-risk patients (with baseline LDL-C >100 mg/dL) achieving the 2019 ESC/EAS LDL-C targets in our simulation, and was associated with the lowest mean cost per patient effectively treated (6,200.1€)."

Clinical • Cardiovascular • Dyslipidemia

Cardiac Allograft Vasculopathy Inhibition with Alirocumab: The CAVIAR Trial. (PubMed, Circulation) - "PCSK9 inhibition with alirocumab in addition to statin therapy early after HT safely lowers LDL-C, but did not reduce coronary artery plaque progression after one year compared with rosuvastatin alone, in patients with a low baseline LDL-C."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders • Transplantation

Antibody-Based Therapeutics for Hypercholesterolemia. (PubMed, Biologics) - "In recent years the mAbs, alirocumab and evolocumab, targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) have become established worldwide as an additional treatment for patients not achieving LDL cholesterol goals on statins and ezetimibe, or sometimes as an alternative treatment in those with statin intolerance...New drug targets were identified to potentially reduce elevated triglyceride levels and the mAb angiopoietin-like 3 (ANGPTL3) inhibitor, evinacumab, was found to be effective in reducing LDL cholesterol in patients with homozygous familial hypercholesterolemia (FH) and has been approved for that indication. SHR-1918 is another mAb targeting ANGPTL3 being developed in China which may also be effective to treat homozygous FH...Another mAb at an early stage of development is MAR001 targeting angiopoietin-like 4 (ANGPTL4). The role for this remains to be established."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • ANGPTL3

Low-Density Lipoprotein Cholesterol Levels after STEMI Complicated by Heart Failure and Prognosis: A Real-World Cohort Study (AHA 2025) - "However, post-hoc analysis of the ODYSSEY OUTCOMES study found that Alirocumab did not reduce the risk of MACE in patients with acute coronary syndrome and a history of heart failure (HF)... In STEMI patients with HF, achieving LDL-C <70 mg/dL after lipid-lowering therapy was associated with reduced recurrent MI risk but a paradoxical increase in mortality. These findings highlight the need to balance the benefits and risks of intensive lipid-lowering, emphasizing the importance of personalized treatment and further research into its long-term effects."

Clinical • Real-world • Real-world evidence • Acute Coronary Syndrome • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Heart Failure • Hypertension • Myocardial Infarction