Leqvio (inclisiran) / Alnylam, Novartis - LARVOL DELTA

siRNA/Inclisiran and the CV continuum - are we reinventing LDL-C management? (ESC-WCC 2025) - "Sponsored by Novartis"

Atherosclerosis • Cardiovascular

VICTORION-Difference study: Inclisiran-based strategy vs standard of care (ESC-WCC 2025) - No abstract available

Cardiovascular

Early PCSK9 inhibitor subscription during episode of acute myocardial infarction (EPISODE-AMI) study (ESC-WCC 2025) - "Purpose: To evaluate the effect of early subscription of a PCSK9 inhibitor, either alirocumab, evolocumab, or inclisiran, during acute phase of AMI on long-term cardiovascular outcomes and medical resources utilization. Early subscription of a PCSK9 inhibitor during acute phase of AMI was associated with a lower risk of MACE, all-cause mortality, and medical utilization."

Acute Coronary Syndrome • Cardiovascular • Myocardial Infarction

VICTORION IMPLEMENT: an observational study of the lipid management landscape in Germany (ESC-WCC 2025) - "Patients in cohort B initiate inclisiran (INCL) according to reimbursement criteria, patients in cohort C initiate INCL on top of lipid apheresis...Patients in cohort A represent a very high ASCVD risk population that is intensively treated with oLLTs, with 83% on statins + ezetimibe and/or bempedoic acid at BL...After the initial dose, INCL lowered LDL-C by 42% in patients not reaching target with max. tolerated oLLT."

Clinical • Observational data • Atherosclerosis • Cardiovascular

Resistance to lipid-lowering therapy with PCSK9 inhibitors: comparative efficacy and clinical implications (ESC-WCC 2025) - "BackgroundPCSK9 inhibitors are recommended as lipid-lowering therapy for patients who do not achieve target LDL cholesterol (LDL-C) levels despite combination therapy with a statin and ezetimibe, as well as for those with statin intolerance...In patients resistant to inclisiran, switching to a monoclonal antibody (alirocumab/evolocumab) may result in better LDL-C reduction, whereas switching from a monoclonal antibody to inclisiran appears less effective. 5. Metabolic factors, genetic predisposition, and baseline lipid parameters do not significantly influence the likelihood of resistance to PCSK9i therapy."

Clinical • Cardiovascular • Dyslipidemia

Adherence to statin therapy after inclisiran start, insights from the the DAMAGE registry (ESC-WCC 2025) - "Stating adherence and reduction of background therapy can impact on the perceived efficacy of inclirisan in reducing LDL-c in the real life. While its efficacy in highly-adherent patients is very close to the one derived from the phase-III clinical trials, efforts should be made in order to mantain background therapy and promote aherence after SiRNA start."

Adherence • Cardiovascular • Dyslipidemia • Myocardial Infarction

Inclisiran: a breakthrough in LDL-C reduction for indian ASCVD patients (ESC-WCC 2025) - "Inclisiran significantly reduced the LDL-C by 70% at three months among Indian ASCVD patients, with greater reductions in VHR patients. A second dose further enhanced the LDL-C lowering to 80% at six months. These findings need validation through larger studies in the Indian population."

Clinical • Cardiovascular

First report of Inclisiran therapy in a heart transplanted patient (ESC-WCC 2025) - No abstract available

Clinical • Cardiovascular • Dyslipidemia

Efficacy of inclisiran in patients affected by familial hypercholesterolemia: data from CHOLINET Registry (ESC-WCC 2025) - "Further pathophysiological mechanisms could be involved in FH, such as genotype, LDL-C receptors residual function and multiple mutations, which might explain the variability in response to inclisiran in patients with FH. However, further studies are needed to better characterize patient with FH and to understand the reasons for high interindividual variations in LDL-C reduction in this population."

Clinical • Cardiovascular • Dyslipidemia

Intensified hypolipidaemic therapy with inclisiran for atherosclerotic plaque stabilization (ESC-WCC 2025) - "Study participants were on high-dose statin (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and optional ezetimibe therapy for 4-6 week run-in period. Intensive pharmacological lipid lowering contributes to plaque stabilization evaluated by NIRS, LDL-C target achievement being important for lipid content reduction. Inclisiran is an effective bailout option for those not fully responsive to statin/ezetimibe."

Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia

Efficacy and safety of inclisiran in patients with and without type 2 diabetes mellitus: a subgroup analysis from the CHOLINET Registry (ESC-WCC 2025) - "This subgroup analysis from the CHOLINET registry confirms inclisiran efficacy in reducing LDL-C, with a greater reduction and higher target achievement in T2DM patients. These findings highlight inclisiran potential role in optimizing lipid management in individuals with T2DM and could be partially explained by the modulation of the asialoglycoprotein receptor, responsible for the uptake of inclisiran into hepatocytes."

Clinical • Cardiovascular • Dyslipidemia • ASGR

Long-term survival of heFH or ACS patients on PCSK9 targeted therapy based on the real-life data from poland (ESC-WCC 2025) - "The current inclusion criteria allow to include heFH pts optimally treated with statins and ezetimibe (for ≥3 months) with LDL-C ≥100 mg/dl, and post-MI pts (within last 24 months) with additional CVD risk factors, treated optimally with statins and ezetimibe for ≥3 months and LDL-C ≥70 mg/dl...The FH pts are mostly treated with alirocumab (43.1%), next with inclisiran (28.5%) and evolocumab (28.4%), and in ACS pts the most common is inclisiran (42.6%), next alirocumab (32.3%) and evolocumab (25.1%)... The PCSK9 targeted therapy drug program showed its extremely high effectiveness in the LDL-C reduction with significant mortality reduction, what is a call for immediate action to apply for its extension to other group of patients at high and very high CVD risk."

Clinical • Cardiovascular • Dyslipidemia

Early experience of inclisiran: real-world analysis of utilization and lipid-lowering effects (ESC-WCC 2025) - " Among 16,531 inclisiran recipients (mean age 71.4 years, 54.4% women, 88.8% White, baseline LDL-C 122.2 mg/dL), 30.2% (n=4,997) only received a single dose, and 86.7% (n=10,004) patients received ≥2 doses on-schedule. In the largest reported analysis to-date of LDL-C changes in patients given inclisiran, those with an LDL-C level ≥155 mg/dL who received three doses on-schedule in the first year experienced LDL-C lowering similar to what was observed in clinical trials after accounting for baseline LDL-C. Those with lower starting LDL-C and on PCSK9i mAb therapy had attenuated LDL-C lowering likely due to changes in background therapy."

Clinical • Real-world • Real-world evidence • Cardiovascular • Dyslipidemia

NLRP3/IL-1 and MyD-88/CCL2 pathway were reduced by inclisiran under exposure to anthracyclines and HER-2 blocking agent (ESC-WCC 2025) - "For the first time, PCSK9i inclisuran exerts significant anti-inflammatory effects to reduce anthracycline-HER-2 blokcing agent mediated cardiotoxicity through NLRP-3 and Myd-88 related pathways. The overall picture of the study warrent on the use of PCSK9i in primary prevention of CTRCD in cancer patients, independently from dyslipidemia."

Cardiovascular • Dyslipidemia • CCL2 • CSF2 • HER-2 • IFNG • IL10 • IL12A • IL17A • IL1B • IL2 • IL4 • IL6 • MYD88 • NLRP3 • RELA • TNFA

Characterization of the pleiotropic effects of Inclisiran (ESC-WCC 2025) - "These findings suggest that Inclisiran may offer additional cardiovascular protection beyond LDL-C reduction. Further studies are needed to confirm these benefits and fully explore their clinical implications."

Atherosclerosis • Cardiovascular • Dyslipidemia • Thrombosis • CCL3 • IL6

Pleiotropic effects of inclisiran on arterial structural and functional parameters (ESC-WCC 2025) - "86.4% were on high-intensity statin therapy and 81.8% on ezetimibe. Inclisiran has been confirmed as an excellent LDL-C lowering drug that also significantly reduces PWV. Studies with a larger number of patients are needed to confirm our findings."

Cardiovascular • Dyslipidemia

VICTORION-Mono China: efficacy and safety of inclisiran as monotherapy in Chinese adults with low or moderate ASCVD risk and elevated LDL-C (ESC-WCC 2025) - "Inclisiran monotherapy was well-tolerated and resulted in sustained and effective reductions in LDL-C and other pro-atherogenic lipids in Chinese patients, establishing it as a potentially useful treatment option for patients at risk of ASCVD."

Clinical • Monotherapy • Cardiovascular • APOB

PCSK9 targeting therapies for familial hypercholesterolaemia: a meta-analysis of efficacy on lipid biomarkers and safety in adults and children across 23 RCTs. (PubMed, Open Heart) - "PCSK9i and Inclisiran demonstrate significant and sustained reductions in LDL-C, ApoB, Lp(a) and TGL in FH patients, especially in heterozygous FH patients. These agents are generally well-tolerated and represent effective treatment options for FH patients inadequately controlled by standard lipid-lowering therapies."

Biomarker • Clinical • Journal • Retrospective data • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Pediatrics • APOB

Optimizing PCSK9 inhibitor therapy: Understanding and managing suboptimal LDL-C response in clinical practice. (PubMed, Eur J Intern Med) - "Under-response may result from insufficient drug exposure due to non-adherence, suboptimal injection technique, or discontinuation of background lipid-lowering therapy, and biological factors that limit drug efficacy despite adequate exposure. This review explores the frequency and mechanisms of under-response to PCSK9-i, and provide a practical guide for clinicians to identify and address causes of PCSK9-i under-response, ensuring appropriate intervention for a sustained cardiovascular risk reduction."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia

The sustainability of hypercholesterolemia treatment: New drugs have made such therapy more expensive. (PubMed, Hipertens Riesgo Vasc) - "The therapeutic landscape for dyslipidemia has evolved substantially in recent years with the introduction of multiple novel agents. Among these, bempedoic acid, characterized by a more favorable cost profile, may serve as a valuable adjunct to statins and ezetimibe, potentially enhancing therapeutic outcomes and minimizing adverse effects-thus delaying or avoiding the need for more costly injectable treatments such as evolocumab, alirocumab, and inclisiran. Ongoing monitoring of prescribing trends and expenditure is crucial to ensuring the sustainability of healthcare systems, facilitating the adoption of innovative and effective treatments while preventing unnecessary resource allocation."

Journal • Cardiovascular • Dyslipidemia • Metabolic Disorders

A Comprehensive Review of the Latest Approaches to Managing Hypercholesterolemia: A Comparative Analysis of Conventional and Novel Treatments: Part II. (PubMed, Pharmaceuticals (Basel)) - "It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe...It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate-citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care."

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

Inclisiran-based treatment strategy in hypercholesterolaemia: the VICTORION-Difference trial. (PubMed, Eur Heart J) - "An inclisiran-based treatment strategy was superior to ioLLT in LDL-C goal achievement, delivering early and sustained LDL-C reduction, with fewer MRAEs in individuals with hypercholesterolaemia. cholesterol, muscle-related adverse events, quality of life, statins."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Pain

Advances in Non-statin Lipid Therapies: A Narrative Review of Evolving Strategies for Cardiovascular Risk Reduction. (PubMed, Am J Cardiovasc Drugs) - "This review examines advances in non-statin lipid-lowering therapies, focusing on proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (monoclonal antibodies and inclisiran), bempedoic acid, and other non-statin lipid medications. We explore emerging therapies targeting novel pathways, including lipoprotein(a), apolipoprotein C-III inhibitors, angiopoietin-like protein 3 (ANGPTL3) inhibitors, cholesteryl ester transfer protein (CETP) inhibitors, and gene-editing technologies. Implementation barriers, including cost considerations, insurance challenges, and global access disparities, are discussed alongside solutions."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • ANGPTL3

Novartis today announced positive results from V-DIFFERENCE, a Phase IV study evaluating Leqvio (inclisiran) compared to placebo, both administered on top of individually optimized lipid-lowering therapy (LLT), in patients with high cholesterol (hypercholesterolemia) who have not achieved guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. (Novartis Press Release) - "After 90 days of treatment with Leqvio on top of LLT, 85% of patients achieved their guideline-recommended LDL-C target compared to 31% of those receiving placebo on top of LLT (p<0.0001). Significant benefits were observed as early as 30 days with 81% of patients achieving LDL-C targets. Results were consistent regardless of age, sex, or cardiovascular risk of trial participants...Patients who received Leqvio plus LLT were 43% less likely to experience muscle-related adverse events (MRAE) compared to patients who received placebo plus LLT (p<0.0001), with numerical improvement in pain-related quality-of-life scores also reported."

P4 data • Heterozygous Familial Hypercholesterolemia

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

New trial • Cardiovascular • Myocardial Infarction