Leqvio (inclisiran) / Alnylam, Novartis - LARVOL DELTA

V-INVINCIBLE: Inclisiran Effectiveness in China: a Pragmatic Randomized Trial (clinicaltrials.gov) - P4 | N=1590 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P4 trial • Cardiovascular • Coronary Artery Disease • Heart Failure • APOB

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

Efficacy and safety of inclisiran based on background lipid-lowering treatment. (PubMed, Eur J Prev Cardiol) - "Sustained and effective LDL-C lowering with inclisiran was observed irrespective of background LLT treatment. Inclisiran was overall well tolerated with all background LLT treatments, consistent with its established safety profile."

Journal • Atherosclerosis • Cardiovascular

Generalizability of VICTORION-1 PREVENT enrollment criteria to the United States population. (PubMed, Am J Prev Cardiol) - "VICTORION-1 PREVENT (V-1P) is an ongoing trial evaluating inclisiran for lipid lowering in patients with high cardiovascular (CV) risk without established atherosclerotic CV disease (ASCVD)...Many primary prevention patients have high CV risk, significant comorbidity burden, and are eligible for lipid-lowering therapy, yet rates of treatment are low. Public health interventions to improve CV risk factor management are necessary."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Metabolic Disorders

TREATMENT WITH INCLISIRAN IN PATIENTS WITH NONFAMILIAL HYPERCHOLESTEROLEMIA AND CHRONIC KIDNEY DISEASE (ERA 2025) - No abstract available

Clinical • Chronic Kidney Disease • Dyslipidemia • Genetic Disorders • Metabolic Disorders • Nephrology • Renal Disease

SOLVE-LDL-C: LDL-C Optimization Using Inclisiran in Patients in Which Drug-Drug Interactions Limit LDL Lowering (clinicaltrials.gov) - P4 | N=100 | Recruiting | Sponsor: University of California, San Diego | Not yet recruiting ➔ Recruiting

Enrollment open • Metabolic Disorders

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

Inclisiran in Cardiovascular Health: A Review of Mechanisms, Efficacy, and Future Prospects. (PubMed, Med Sci Monit) - "For instance, its long-term safety and efficacy require further investigation in future studies, and its high cost can restrict its widespread adoption and promotion. Furthermore, additional clinical evidence is needed to evaluate its synergistic or antagonistic effects when used in conjunction with other medications."

Journal • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders • Oncology

Efficacy and outcomes of inclisiran in the management of homozygous and heterozygous familial hypercholesterolemia: a systematic review and meta-analysis. (PubMed, Ann Med Surg (Lond)) - "There was a significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of inclisiran except for the PCSK9 parameter. Further studies are needed to support this conclusion."

Journal • Retrospective data • Atherosclerosis • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Optimising Secondary Prevention in Patients Undergoing Carotid Surgery: A Cohort Study Assessing Lipid Lowering Therapy and Antithrombotic Therapy Odd page running title: Cardiovascular Prevention Medications in Carotid Surgery Patients. (PubMed, Eur J Vasc Endovasc Surg) - "Underutilisation of LLT prior to incident stroke was identified as a key tractable problem. Admission for carotid intervention is associated with an increase in GDMT and reduction in LDL-C levels. There is scope for improvement and a need for long term community based management of cardiovascular risk, specifically risk assessment, initiation and ongoing uptitration of LLT, and regular monitoring of LDL-C levels."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia

Safety and effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition: an updated review. (PubMed, Curr Opin Lipidol) - "PCSK9i remain integral in ASCVD risk reduction, given their potent LDL-C-lowering effects, all while maintaining a favorable safety profile. The greatest benefits are observed in patients with AMI, particularly in multivessel disease. Despite high adherence, broader utilization is hindered by persistent challenges, including costs and complex authorization processes."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Myocardial Infarction

Anti-interleukin-5 efficacy in an inclisiran-triggered eosinophilic myocarditis: a case report. (PubMed, Eur Heart J Case Rep) - "The patient was initially treated with itraconazole and steroid therapy...Mepolizumab, an interleukin-5 (IL-5) inhibitor, was initiated resulting in symptom resolution and absence of inflammation at the 6-month follow-up CMR. This case describes an uncommon response to inclisiran that resulted in Aspergillus-induced, steroid-dependent, eosinophilic systemic inflammation, resulting in severe asthma and endocarditis. It demonstrates how biological IL-5 inhibitors are effective in treating both components, emphasizing the necessity of a multidisciplinary strategy."

Journal • Allergic Bronchopulmonary Aspergillosis • Asthma • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Eosinophilia • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • IL5

Use of Inclisiran as Lipid-Lowering Therapy in a Heart Transplant Recipient (ISHLT 2025) - "The emergence of novel non-statin therapies (PCSK9 inhibitors such as alirocumab and evolocumab, and more recently, small interfering RNA therapy such as inclisiran) have expanded our repertoire for treatment of dyslipidemia...After transplant, he has been successfully maintained on pravastatin 10 mg daily for CAV prophylaxis without complaints of memory loss...Given the targeted mechanism of action, no drug interactions or interference with immunosuppressive therapy should be anticipated. Future studies should address whether inclisiran may provide CAV risk reduction or cardiovascular mortality benefit in heart transplant recipients."

Clinical • Cardiomyopathy • Cardiovascular • Coronary Artery Disease • Diabetes • Dyslipidemia • Metabolic Disorders • Musculoskeletal Pain • Pain • Transplantation • Type 2 Diabetes Mellitus

V-DIFFERENCE: Study of Efficacy, Safety, Tolerability and Quality of Life of Inclisiran (KJX839) vs Placebo, on Top of Ongoing Individually Optimized Lipid-lowering Therapy, in Participants With Hypercholesterolemia (clinicaltrials.gov) - P4 | N=1776 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Familial Hypercholesterolemia • Metabolic Disorders

NHS increases funding for inclisiran although uptake remains ‘slower than expected’ (Pharm J) - "NHS England has increased funding for inclisiran (Leqvio; Novartis), with community pharmacies now able to purchase the anticholesterol drug at a nominal charge of £45 and be reimbursed at £60 — an increase from £50....In a letter on cardiovascular disease (CVD) prevention sent to NHS colleagues on 31 March 2025, NHS England said the funding had been aligned to the new pharmacy contract and would be effective as of 1 April 2025....As part of this priority, NHS England said it had 'renegotiated an agreement with Novartis for continued access to inclisiran, maintaining the same price for current and new NHS patients in England until December 2027'....In additional information on the funding and supply of inclisiran, NHS England said it had agreed to continue to fund inclisiran centrally for all patients initiated on treatment up to 31 December 2027, at which point the agreement will be assessed and any changes from 1 January..."

Reimbursement

Novartis' lipid-lowering drug Leqvio clears reimbursement hurdle on 1st attempt (Korea Biomedical Review) - :"Novartis' twice-yearly lipid-lowering subcutaneous injection Leqvio (inclisiran) has passed the Pharmaceutical Reimbursement Evaluation Committee (PREC) on its first challenge....The Health Insurance Review and Assessment Service (HIRA) held the fourth PREC meeting for 2025 on Thursday and released these and other results....However, Leqvio received a conditional approval. The government deemed the drug eligible for reimbursement at a lower price. If Novartis accepts the condition, the drug will be reimbursed pending price negotiations with the National Health Insurance Service and final approval by the Health Insurance Policy Review Committee of the Ministry of Health and Welfare."

Reimbursement • Dyslipidemia • Heterozygous Familial Hypercholesterolemia

Backed by LEQVIO® (inclisiran) Data: Why Adherence Matters - KaJuan Billings (ACC 2025) - "Sponsored by Novartis Pharmaceuticals Corporation"

Adherence

Backed by LEQVIO® (inclisiran) Data: Why Adherence Matters - David Kwon (ACC 2025) - "Sponsored by Novartis Pharmaceuticals Corporation"

Adherence

4012 - Backed by LEQVIO® (inclisiran) Data: Why Adherence Matters (ACC 2025) - "This insightful presentation will explore the importance of adherence and how LEQVIO can be used in appropriate patients.Industry-Expert Theater presentations are not part of ACC.25, as planned by its Program Committee, and do not qualify for continuing medical education (CME), continuing nursing education (CNE) or continuing education (CE) credit. Sponsored by Novartis Pharmaceuticals Corporation"

Adherence

THE IMPACT OF ADHERENCE TO LDL-C LOWERING THERAPIES ON CARDIOVASCULAR EVENTS AMONG ADULTS WITH ATHEROSCLEROTIC CARDIOVASCULAR DISEASE, HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA AND PRIMARY HYPERLIPIDEMIA - Robert S. Rosenson (ACC 2025) - "Better real-world adherence to inclisiran versus PCSK9 mAbs was projected to prevent ~28% more CV events among US adults with ASCVD, HeFH and PH."

Adherence • Clinical • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders

LOSS OF EFFICACY WITH ALIROCUMAB AFTER TWO YEARS OF TREATMENT IN A PATIENT WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HEFH) - Erika Hellenbart (ACC 2025) - "Here, we describe a case showing significant loss of efficacy of alirocumab following two years of therapy.Case: We present a 29 year-old female with HeFH; baseline LDL of 136 mg/dL on rosuvastatin 40 mg daily and ezetimibe 10 mg daily...Given a previously reported rash with evolocumab, no commercial test for antidrug antibodies, alirocumab was changed to inclisiran in March of 2024... Loss of efficacy to alirocumab was overcome by switching to inclisiran which interferes with PCSK9 protein translation rather than blocking the receptor site. We do not expect the oral contraceptive changes to account for such dramatic changes in LDL. This case reinforces ongoing lipid monitoring even when LDL goals are met."

Clinical • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Polycystic Ovary Syndrome

COMPARATIVE EFFICACY, SAFETY, AND LONG-TERM OUTCOMES OF INJECTABLE CHOLESTEROL-LOWERING AGENTS: A NETWORK META-ANALYSIS OF ALIROCUMAB, EVOLOCUMAB, INCLISIRAN, AND MIPOMERSEN - Rakhshanda Khan (ACC 2025) - "Risk of bias was assessed using ROB 2.0. PCSK9 inhibitors, including Alirocumab, Evolocumab, Bococizumab, and Inclisiran, significantly reduced LDL-C levels, with reductions over 60%. PCSK9 inhibitors, particularly alirocumab and evolocumab, significantly reduce LDL-C and lower the risk of myocardial infarction, stroke, and revascularization. These agents provide a promising adjunct to statin therapy in high-risk patients with a favorable safety profile, supporting their role in improving long-term CV outcomes. Further research is needed on their long-term cost-effectiveness and clinical impact."

Retrospective data • Atherosclerosis • Cardiovascular • Myocardial Infarction

STATIN-INDUCED RHABDOMYOLYSIS IN A PATIENT WITH HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA: A CASE REPORT AND CLINICAL IMPLICATIONS - Henrique T. Bianco (ACC 2025) - "Than, the patient was initiated on a combination therapy of Simvastatin 20/Ezetimibe 10. After 30 days, she was admitted to a hospital with generalized myalgia, She had abdominal pain, and altered mental status. Treatment with inclisiran, which suppresses hepatic PCSK9 synthesis, can dramatically reduce LDL cholesterol fraction levels and can be administered in injectable form every six months. Studies reveal that with just two annual applications, it is possible to reduce LDL levels by an average of 52%."

Case report • Clinical • Dyslipidemia • Endocrine Disorders • Familial Hypercholesterolemia • Genetic Disorders • Heterozygous Familial Hypercholesterolemia • Metabolic Disorders • Musculoskeletal Pain • Pain • MB

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

COMBINATION THERAPY WITH SEMAGLUTIDE AND PCSK9I REDUCES SYNERGISTICALLY ANTHRACYCLINE-INDUCED CARDIOTOXICITY UNDER HYPERLIPIDEMIA: IMPLICATIONS IN PRIMARY PREVENTION OF CTRCD IN CANCER PATIENTS - Nicola Maurea (ACC 2025) - "For the first time, combination therapy with Semaglutide and PCSK9i inclisiran was effective and superior, compared to monotherapy, to reduce anthracycline-mediated cardiotoxicity through different signalling pathways."

Clinical • Combination therapy • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • Oncology • CSF2 • IFNG • IL10 • IL12A • IL17A • IL1B • IL2 • IL4 • IL6 • MYD88 • NLRP3 • RELA • TLR4 • TNFA