Leqvio (inclisiran) / Alnylam, Novartis - LARVOL DELTA

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

ORION-4: A Randomized Trial Assessing the Effects of Inclisiran on Clinical Outcomes Among People With Cardiovascular Disease (clinicaltrials.gov) - P3 | N=16124 | Active, not recruiting | Sponsor: University of Oxford | Trial primary completion date: Jul 2026 ➔ Oct 2026

Trial primary completion date • Atherosclerosis • Cardiovascular

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

Achieving the impossible: effective reduction of low-density lipoprotein cholesterol (LDL-C) in a patient with homozygous familial hypercholesterolemia. (PubMed, Endokrynol Pol) - "Not required for Clinical Vignette."

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

Class-Specific Adverse Events of Patients Treated with Small Interfering RNA Therapeutics: A Disproportionality Analysis of the United States Food and Drug Administration Adverse Event Reporting System Database Based on the MY FAERS Platform. (PubMed, Nucleic Acid Ther) - "This study aimed to identify and quantify CAE-siRNA associated with U.S. Food and Drug Administration (FDA)-approved siRNA drugs (patisiran, givosiran, vutrisiran, inclisiran, and lumasiran) using real-world pharmacovigilance data, focusing on potential class-wide effects. This study identified clinically relevant CAE-siRNA, particularly hepatic toxicity for inclisiran, supporting enhanced monitoring. While disproportionality analyses are hypothesis generating, these findings underscore the need for targeted pharmacovigilance to optimize the safety of this promising drug class."

Adverse events • Journal • Back Pain • Fatigue • Gastroenterology • Gastrointestinal Disorder • Musculoskeletal Pain • Pain

A universal LC-HRMS workflow integrating targeted and untargeted strategies for rapid and comprehensive metabolite profiling of oligonucleotide-based therapeutics. (PubMed, J Pharm Biomed Anal) - "Product ion spectra of these metabolites showed weak or absent diagnostic ion (m/z 94.936), a characteristic fragment of phosphorothioate-containing oligonucleotides, suggesting that the product ion filtering of this ion exhibits limited utility in discovering inclisiran metabolites. Overall, the integrated LC-HRMS workflow shows strong potential as a universal platform for biotransformation studies of OBTs."

Journal

STREAMLINE: Evaluation of 1-Year Clinical Outcomes With Early Inclisiran Initiation in Post-MI Patients (clinicaltrials.gov) - P=N/A | N=300 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Myocardial Infarction

ACS: Evaluation of Efficacy and Safety of Early in Hospital Initiation of Inclisiran Treatment in Patients With Acute Coronary Syndromes (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Coronary Syndrome • Cardiovascular • APOB

A Non-interventional Implementation Study to Evaluate Treatment With Inclisiran (Leqvio®) and Other Lipid Lowering Treatments in a Real-world Setting (clinicaltrials.gov) - P=N/A | N=1871 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Real-world evidence • Trial completion • Dyslipidemia • Metabolic Disorders

Paradoxical LDL-C Increase after Switching from PCSK9 Inhibitors to Inclisiran: A Real-World Case Series. (PubMed, Acta Cardiol Sin) - No abstract available

Journal • Real-world evidence

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

Muscle Adverse Events Associated with Inclisiran: Data Mining of FAERS database and Mendelian Randomization Analysis. (PubMed, J Cardiovasc Pharmacol) - "This study revealed that MAEs associated with Inclisiran. Additional laboratory and clinical monitoring should be considered for patients taking Inclisiran for timely diagnosis and management of MAEs."

Adverse events • Journal • Musculoskeletal Diseases • Musculoskeletal Pain • Pain

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

Real-World Adherence and Effectiveness of Inclisiran in Lowering LDL-C: Results from 1 Year of Follow-Up. (PubMed, Cardiol Ther) - "Inclisiran significantly reduced LDL-C. The dosing schedule promoted high adherence in a real-world setting, particularly among older adults with ASCVD. These findings indicate inclisiran may be a particularly valuable addition to lipid-lowering strategies."

HEOR • Journal • Real-world evidence • Atherosclerosis • Cardiovascular • Dyslipidemia

Reduction of visit-to-visit LDL-C intraindividual variability in patients treated with PCSK9 inhibitors and inclisiran vs standard lipid-lowering therapy. (PubMed, J Clin Lipidol) - "In patients at very high cardiovascular risk, PCSK9i and inclisiran therapies are associated with significantly lower visit-to-visit LDL-C variability compared to standard statin-based regimens. These findings support the importance of not only achieving LDL-C targets but also maintaining lipid stability over time, which may contribute to improved cardiovascular outcomes."

Journal • Cardiovascular • Dyslipidemia

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

Novartis will present new data from 33 abstracts across its Cardiovascular, Renal, and Metabolic (CRM) disease portfolio at the upcoming American Society of Nephrology (ASN) Kidney Week 2025 in Houston, Texas and American Heart Association’s (AHA) Scientific Sessions 2025 in New Orleans, Louisiana, advancing scientific insight into these critical disease areas (Novartis Press Release)

Clinical data • Autosomal Dominant Polycystic Kidney Disease • Cardiovascular • Chronic Kidney Disease • IgA Nephropathy

Post-Event* LDL-C Management Strategies: Expert Perspectives on LEQVIO® (inclisiran) (AHA 2025) - "Sponsored By: Novartis Pharmaceutical CorporationThis event is not part of the official Scientific Sessions Conference 2025 as planned by the American Heart Association Committee on Scientific Sessions Programming"

Dyslipidemia

Post-Event* LDL-C Management Strategies: Expert Perspectives on LEQVIO® (inclisiran) (AHA 2025) - "Sponsored By: Novartis Pharmaceutical CorporationThis event is not part of the official Scientific Sessions Conference 2025 as planned by the American Heart Association Committee on Scientific Sessions Programming"

Dyslipidemia

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