Waylivra (volanesorsen) / Ionis, Novartis, PTC Therapeutics, SOBI - LARVOL DELTA

Volanesorsen as an Effective Therapy in Familial Chylomicronemia Syndrome (AHA 2026) - "Abstract is embargoed at this time."

Familial Chylomicronemia Syndrome

Apolipoprotein C-III inhibition reduces acute pancreatitis in familial chylomicronemia syndrome: a meta-analysis of randomized trials (ESC 2026) - " PubMed, Embase, and Cochrane Library were systematically searched through December 2025 for randomized controlled trials enrolling patients with FCS treated with ApoC-III inhibitors (volanesorsen, olezarsen, plozasiran). In patients with FCS, ApoC-III inhibition produces profound and sustained triglyceride lowering and significantly reduces acute pancreatitis risk with an acceptable safety profile. These findings support ApoC-III–targeted therapy as a disease-modifying strategy in FCS, shifting management from dietary restriction alone toward effective pharmacologic prevention of recurrent pancreatitis."

Retrospective data • Cardiovascular • Dyslipidemia

Comparative efficacy of APOC3- and ANGPTL3-targeted therapies in severe hypertriglyceridemia: a systematic review and network meta-analysis (ESC 2026) - "Publication bias was evaluated through funnel plot analysis Results Olezarsen 80 mg, Olezarsen 50 mg, Plozasiran 10 mg, Plozasiran 25 mg, Plozasiran 50 mg, and Volanesorsen 300 mg were all significantly superior to placebo in reducing triglyceride levels (Figure 1). Conclusions This systematic review and network meta-analysis indicate Volanersorsen and higher doses of Olezarsen are most effective in reducing TG. Meanwhile, Olezarsen and Plozasiraan have greater effect in decreasing Acute Pancreatitis incidence, suggesting Olazarsen may be a preferable treatment for hypertriglyceridemia."

Retrospective data • Review • Cardiovascular • Dyslipidemia • ANGPTL3

Familial Chylomicronemia Syndrome Due to a Homozygous LPL c.644G>A Variant and Response to Volanesorsen in Colombia: A Case Report. (PubMed, Cureus) - "This case underscores the importance of suspecting FCS in patients with refractory severe hypertriglyceridemia and recurrent pancreatitis. Molecular diagnosis enables access to precision medicine-based strategies with a meaningful impact on clinical outcomes and quality of life."

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia

Comparative efficacy and safety of olezarsen versus volanesorsen for familial chylomicronemia syndrome: a matching-adjusted indirect comparison. (PubMed, J Comp Eff Res) - " In this matching-adjusted indirect comparison, no statistically significant differences in outcomes were observed between olezarsen and volanesorsen in patients with FCS. These findings provide important comparative context in a setting where head-to-head evidence is unavailable."

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • LPL

Triglyceride Lowering Treatment with Apolipoprotein C3 Inhibitors and Pancreatitis: A Meta-Analysis of Randomized Trials (ENDO 2026) - " 13 placebo controlled randomized trials evaluating ApoC-3 inhibitors (Olezarsen, Plozasiran, Volanesorsen) in patients with either primary or secondary hypertriglyceridemia were included (inception-December 2025). ApoC-3 inhibitors significantly reduced TGs levels and risk of pancreatitis."

Retrospective data • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Thrombocytopenia • APOC3

Navigating hypertriglyceridemia in pregnancy: current evidence and clinical strategies. (PubMed, Front Endocrinol (Lausanne)) - "While olezarsen is not recommended, two case reports describe successful and safe use of volanesorsen in pregnant women with familial chylomicronemia syndrome under close monitoring. This narrative review synthesizes current evidence on the pathophysiology, prognostic implications, and management of hypertriglyceridemia in pregnancy, emphasizing early risk identification, first-trimester lipid assessment, and individualized treatment aligned with the updated ESC/EAS guidelines."

Journal • Review • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Gynecology • Hypertension • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

Metabolic Targets APOC3 and GCK Influence Antipsychotic Efficacy in Schizophrenia (APA 2026) - "Conclusions The present study revealed that APOC3-proxied lipid-lowering enhanced antipsychotic efficacy, whereas GCK-related glucose reduction was associated with worse therapeutic outcomes. We firstly suggested that volanesorsen / olezarsen as potential adjunctive candidates, dorzagliatin warrants prudence in SCZ complicated by metabolic disturbance."

Clinical • CNS Disorders • Diabetes • Dyslipidemia • Metabolic Disorders • Psychiatry • Schizophrenia

Targeting triglycerides for cardiovascular risk reduction. (PubMed, Intern Emerg Med) - "By contrast, icosapent ethyl, a highly purified ethyl ester of eicosapentaenoic acid, is the only TRL-targeted therapy that has demonstrated a significant reduction in major cardiovascular events in a large, randomized trial, irrespective of baseline triglyceride levels. Novel agents such as evinacumab (an ANGPTL3 monoclonal antibody) and antisense oligonucleotides against apolipoprotein C-III (volanesorsen, olezarsen, plozasiran) have produced marked decreases in triglycerides, apoB-containing lipoproteins and remnant cholesterol in recent clinical studies, even though cardiovascular outcome data are not yet available. Therefore, therapies targeting TRL metabolism represent a promising approach to reduce residual cardiovascular risk, particularly in high-risk or statin-treated patients."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • ANGPTL3 • APOB

The evaluation of plozasiran for the treatment of familial chylomicronemia syndrome. (PubMed, Expert Rev Endocrinol Metab) - "We searched PubMed for all English language literature focusing on the search terms 'chylomicronemia,' 'hypertriglyceridemia,' 'APOC3 inhibition,' 'plozasiran,' 'olezarsen,' and 'volanesorsen.' We outline traditional management strategies and their limited role in FCS and explore non-traditional therapies including orlistat, lomitapide, inhibitors of angiopoietin like protein 3 (ANGPTL3), and analogues of fibroblast growth factor 21 (FGF21). In a phase 3 trial of plozasiran, at 10 months, median placebo-adjusted reductions in apo C-III were approximately -90%, while TG levels were reduced up to -59%. Thus, plozasiran and alternative RNA-based therapeutics directed against APOC3 represent transformational therapies for patients with FCS and related phenotypes characterized by severe recalcitrant hypertriglyceridemia."

Journal • Review • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • ANGPTL3 • FGF21

Current and Emerging Pharmacological Therapies for Hypertriglyceridemia. (PubMed, Int J Mol Sci) - "Emerging therapies such as antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) directed against ApoC-III (volanesorsen, olezarsen, and plozasiran), inhibitors of ANGPTL3 (evinacumab and zodasiran), and fibroblast growth factor 21 (FGF-21) analogs (pegozafermin) have demonstrated substantial triglyceride-lowering efficacy. The therapeutic landscape for hypertriglyceridemia is rapidly evolving. Integrating these novel agents into clinical practice will require individualized treatment plans, sustained lifestyle modification, and careful safety monitoring."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • ANGPTL3 • FGF21 • LPL

Efficacy and Safety of Apolipoprotein C-III Inhibitors in Hypertriglyceridemia: A Network Meta-Analysis of Randomised Controlled Trials. (PubMed, Diabetes Obes Metab) - "ApoC-III inhibitors significantly improved triglyceride levels and other lipid parameters and, most importantly, substantially reduced the risk of acute pancreatitis. Future trials are needed to evaluate their effects on cardiovascular outcomes."

Journal • Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Pancreatitis

Oligonucleotides: Evolution of Carcinogenicity and Risk Assessment Strategy. (PubMed, Toxicol Pathol) - "Nevertheless, for eplontersen and olezarsen, carcinogenicity assessment was limited to a single Tg.rasH2 mouse study or fully waived, supported by prior two-species carcinogenicity data from inotersen and volanesorsen. With the recent ICH S1B(R1) addendum, sponsors now have a defined pathway to pursue carcinogenicity strategies, including potential waivers of the 2-year rat study when supported by the totality of evidence. This article reviews the evolving landscape of ASO carcinogenicity testing and highlights opportunities to reduce or waive long-term studies."

Journal • Review • Oncology

Lipid-lowering and glucose-lowering drug targets differentially modulate antipsychotic treatment efficacy in schizophrenia. (PubMed, Cell Rep Med) - "Genetically proxied proteomics analysis provides further functional validation for the identified target-outcome associations. Our findings suggest volanesorsen/olezarsen as potential adjunctive candidates; dorzagliatin warrants prudence in schizophrenia with metabolic disturbance."

Journal • CNS Disorders • Diabetes • Dyslipidemia • Metabolic Disorders • Psychiatry • Schizophrenia

Case Report: Conventional therapy versus volanesorsen in two sisters with familial chylomicronemia syndrome. (PubMed, Front Nutr) - "She presented persistent hypertriglyceridemia and recurrent hospitalizations, underscoring the challenges of access to advanced therapies in limited-resource settings. While volanesorsen offers a promising therapeutic alternative, equitable access remains a critical issue, particularly in health systems of low-to middle-income regions."

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia • APOA5

Efficacy and safety of antisense oligonucleotide therapies targeting APoC-III in patients with severe hypertriglyceridemia: a meta-analysis of randomized controlled trials. (PubMed, Monaldi Arch Chest Dis) - "Antisense oligonucleotide (ASO) therapies like volanesorsen and olezarsen target ApoC-III mRNA to reduce ApoC-III, enhancing lipoprotein lipase activity and lowering triglycerides (TGs). Acute pancreatitis occurred only in the placebo group (relative risk: 0.15; p=0.0004), indicating ASO protection. This meta-analysis confirms that ASOs effectively lower TGs and improve lipid profiles in severe HTG."

Journal • Retrospective data • Cardiovascular • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia • APOB • LPL

From physiopathology to treatment of familial hypercholesterolemia: Existing and emerging pharmacotherapies. (PubMed, Pharmacol Rev) - "This includes established drugs such as proprotein convertase subtilisin/kexin type 9 inhibitors, inclisiran, lomitapide, and bempedoic acid. Emerging therapies include evinacumab, lerodalcibep, antisense oligonucleotide-based drugs, certain cholesteryl ester transfer protein inhibitors like obicetrapib, AZD8233, gemcabene, diacylglycerol O-acyltransferase-2 inhibitors, acyl-CoA:cholesterol acyltransferase-2 inhibitors, vupanorsen, volanesorsen, olezarsen, pelacarsen (TQJ230), olpasiran (AMG890), zerlasiran (SLN360), lepodisiran (LY3819469), and muvalaplin...Recent pharmacological advancements provide significant opportunities for successful low-density lipoprotein cholesterol management and control of FH. Although some of these agents are already used, several highly effective compounds are in development, heralding a promising future for FH treatment."

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

2025: The year in cardiovascular disease - the year of triglyceride lowering therapies. Can we effectively reduce triglyceride-related residual cardiovascular disease and pancreatitis risk? (PubMed, Arch Med Sci) - "Novel agents targeting apolipoprotein C-III (volanesorsen, olezarsen, plozasiran) achieve profound triglyceride declines and substantially mitigate pancreatitis in familial chylomicronemia syndrome (FCS), while angiopoietin-like 3 (ANGPTL3) inhibitors and fibroblast growth factor 21 (FGF21) agonists demonstrate early promise in broad atherogenic-lipid reduction and metabolic modulation. Current guidelines endorse icosapent ethyl and fenofibrate for high-risk HTG, with apoC-III inhibitors poised to become first-line for FCS as access improves. Ongoing trials of ANGPTL3 inhibitors, FGF21 agonists and gene-editing approaches may soon redefine lifelong lipid management."

Journal • Atherosclerosis • Atrial Fibrillation • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Inflammation • Metabolic Disorders • Mixed Hyperlipidemia • Pancreatitis • ANGPTL3 • FGF21

A delayed diagnosis of familial chylomicronemia syndrome in an elderly patient: Clinical implications of late-onset disease. (PubMed, J Clin Lipidol) - "Recognition of characteristic biochemical profiles and family history is essential to avoid diagnostic delay and prevent irreversible pancreatic damage and malnutrition. Even in elderly patients, targeted therapy can substantially improve metabolic control and quality of life."

Journal • Chronic Kidney Disease • Cognitive Disorders • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Metabolic Disorders • Nephrology • Pancreatitis • Renal Disease • Severe Hypertriglyceridemia • LPL

Efficacy and Safety of Olezarsen in Patients With Hypertriglyceridemia: A Meta-Analysis of Randomized Controlled Trials. (PubMed, Cardiovasc Ther) - "Novel drugs that target apoC-III in lipoprotein metabolism to reduce plasma triglycerides are currently under development. Although it performed well compared to volanesorsen, inconsistencies in LDL reduction and heterogeneity in some groups warrant further large-scale RCTs to better assess its safety and efficacy. Clinical decisions should be tailored to individual patient profiles, as hypertriglyceridemia management may vary on a case-to-case basis."

Biomarker • Clinical • Journal • Retrospective data • Review • Dyslipidemia • Hypertriglyceridemia

Improvement of severe hypertriglyceridemia in atypical subtype 4 partial lipodystrophy with volanesorsen. (PubMed, J Clin Lipidol) - "Recurrent severe hypertriglyceridemia and normal leptin levels prompted the use of volanesorsen therapy, which is primarily indicated for treatment of hypertriglyceridemia in familial chylomicronemia syndrome. Volanesorsen proved very effective in this case."

Journal • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Hepatology • Hypertension • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Pulmonary Arterial Hypertension • Severe Hypertriglyceridemia • LEP

Approach to the Adult Patient with Chylomicronemia. (PubMed, J Clin Endocrinol Metab) - "Emerging RNA-based therapies targeting apolipoprotein C-III (e.g., volanesorsen, olezarsen and plozasiran) offer transformative potential for FCS and for some refractory patients with other chylomicronemia subtypes. A multidisciplinary approach-integrating clinical, biochemical, and genetic assessment-guides therapy and reduces pancreatitis risk."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Immunology • Lipodystrophy • Metabolic Disorders • Pain • Pancreatitis • APOB

Anti-PF4 antibodies are a potential mediator of antisense oligonucleotide (ASO)-induced thrombocytopenia. (ASH 2025) - "Twelve ASOs, Inotersen, Eplontersen,Olezarsen, Fomivirsen, Mipomersen, Tofersen, Nusinersen, Eteplirsen, Golodirsen, Viltolarsen,Casimersen (all FDA approved) and Volanesorsen (EMA approved) were evaluated in this study. With two ASOs, Fomivirsen and Eteplirsen, direct activation of platelets was noted. Studieswith additional ASOs revealed a novel immune mechanism involving ASO-PF4 complex formation andanti-PF4 antibody recognition that can plausibly mediate ASO-induced thrombocytopenia. These findingshighlight the key role PS linkages may play in ASO immunogenicity and provide a mechanistic frameworkfor risk mitigation in ASO drug design, supporting the safer development and broader application of ASOtherapeutics."

Hematological Disorders • Thrombocytopenia

An Updated Review of Novel Triglyceride-Lowering Therapies in Adults with Familial Chylomicronemia Syndrome. (PubMed, Am J Cardiovasc Drugs) - "A literature search in PubMed and EMBASE was conducted from January 2013 to July 2025 using keywords "familial chylomicronemia syndrome", "olezarsen", "volanesorsen", and "plozasiran". These new apoC-III lowering medications provide a novel treatment approach for patients with FCS, a population long without effective pharmacological treatment options. Provider familiarity with the availability and purpose of these medications will allow patients to receive the best therapy available to manage FCS."

Journal • Review • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis

Lessons from recent clinical trials for the prevention of acute pancreatitis in chylomicronemia syndromes. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "These emerging mechanism-based therapies are reshaping the management of severe hypertriglyceridemia, offering targeted approaches to reduce triglycerides and acute pancreatitis risk. Ongoing studies will clarify long-term safety, durability of response, and optimal patient selection, providing a framework for improved clinical outcomes."

Journal • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pancreatitis • Severe Hypertriglyceridemia • ANGPTL3 • FGF21 • LPL