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

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

Optimized diet in a patient with familial chylomicronemia syndrome (FCS) with increased energy requirements receiving Volanesorsen (SSIEM 2023) - No abstract available

Clinical • Familial Chylomicronemia Syndrome

Optimized diet in a patient with familial chylomicronemia syndrome (FCS) with increased energy requirements receiving Volanesorsen (SSIEM 2023) - No abstract available

Clinical • Familial Chylomicronemia Syndrome

Optimized diet in a patient with familial chylomicronemia syndrome (FCS) with increased energy requirements receiving Volanesorsen (SSIEM 2023) - No abstract available

Clinical • Familial Chylomicronemia Syndrome

Optimized diet in a patient with familial chylomicronemia syndrome (FCS) with increased energy requirements receiving Volanesorsen (SSIEM 2023) - "In addition to pharmacological therapy a strict low-fat diet is required. A TG-level of around 450 mg/dl can be achieved with adherence to a very low-fat diet and Volanesorsen-treatment, even with increased energy requirements."

Clinical • Familial Chylomicronemia Syndrome • Genetic Disorders • Pancreatitis • Pediatrics • LPL

Anti-apoC-III Therapies and Implications for Treatment of Pancreatitis and Cardiovascular Disease. (PubMed, Curr Atheroscler Rep) - "APOC3 inhibition is now an established therapeutic approach for reducing the risk of acute pancreatitis in FCS, with three agents, volanesorsen, olezarsen, and plozasiran, demonstrating efficacy. However, its role in ASCVD prevention remains unproven. This review evaluates current APOC3 - targeted therapies for FCS, including available comparative data, and synthesizes the emerging literature on the potential of APOC3 inhibition to reduce the burden of acute pancreatitis in broader populations with severe hypertriglyceridemia, as well as its potential role in ASCVD risk reduction."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • LPL

Contemporary Management of Familial and Multifactorial Chylomicronemia Syndromes in Italy: Insights From the National Lipigen Registry. (PubMed, Arterioscler Thromb Vasc Biol) - "As compared with MCS, patients with FCS showed a more severe phenotype and higher prevalence of LPL variants. Lomitapide and volanesorsen provide better triglyceride control, yet only one-third of FCS were treated with these drugs in the routine clinical practice."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • APOA5

Dyslipidemias as rare diseases. (PubMed, Cas Lek Cesk) - "Thanks to new hypolipidemic drugs such as evinacumab and lomitapide, patients today have a much better prognosis than in the past...Due to new causal metreleptine therapy, we can help patients with managing these metabolic complications significantly...Therapy with volanesorsen leads to a reduction of hypertriglyceridemia, thereby reducing the risk of developing acute pancreatitis. Although these diseases are rare, it is necessary to think about them and diagnose them early. Interdisciplinary cooperation is essential during search and treatment of these patients."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases

ApoC-III as Therapeutic Target: Is it Primetime for Clinical Use? (PubMed, Curr Atheroscler Rep) - "Current treatments targeting Apo C-III include two antisense oligonucleotides (ASOs) (volanesorsen and olezarsen), and a small interfering RNA (siRNA) (plozasiran). ApoC-III inhibition represents an innovative and effective approach in managing hypertriglyceridaemia and its complications. Further outcome-driven trials are essential to define its role in cardiovascular risk reduction."

Journal • Review • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Pancreatitis • Thrombocytopenia • LPL

Recurrent Hypertriglyceridemia-induced Acute Pancreatitis Hiding Familial Hyperchylomicronemia Syndrome (ENDO 2025) - "This case emphasizes the importance of diagnosing FCS in patients with recurrent pancreatitis and elevated triglycerides. Genetic testing confirmed the diagnosis, leading to appropriate management with insulin, fenofibrate, and specialized care."

Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Hypertriglyceridemia • Hypoglycemia • Pain • Pancreatitis • LPL

Experience with apheretic treatment in the chronic management of severe hypertriglyceridemia: case series. (PubMed, Endocrine) - "During this time, new therapeutic agents such as volanesorsen and lomitapide became available. However, none of these patients met the reimbursement criteria set by the Italian Medicines Agency (AIFA). We describe the clinical management and follow-up of these patients, in whom plasma and lipoprotein apheresis remain an effective therapy for reducing the risk of pancreatitis."

Journal • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

Real life evidence of volanesorsen for familial chylomicronemia syndrome in Colombia. (PubMed, J Clin Lipidol) - "Real-life data of volanesorsen treatment for FCS in Colombia demonstrate efficacy and safety similar to pivotal clinical trials."

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Rare Diseases • Severe Hypertriglyceridemia • APOA5

Budget Impact Analysis of Volanesorsen as a Complement to the Diet in Adult Patients with Familial Chylomicronemia Syndrome (FCS) in Mexico (ISPOR 2025) - "The inclusion of volanesorsen in the public health sector in Mexico increases the therapeutic options available for patients with FCS. Given the low prevalence of this disease, the results of the analysis indicate that its incorporation is economically viable, representing a reasonable investment to address an uncovered clinical condition."

Clinical • HEOR • Familial Chylomicronemia Syndrome • Pancreatitis

Novel Therapeutics for Familial Chylomicronemia Syndrome. (PubMed, Curr Atheroscler Rep) - "Volanesorsen, an ASO targeting APOC3, has shown effectiveness in managing FCS, multifactorial chylomicronemia, and familial partial lipodystrophy, but its use is limited by thrombocytopenia. Emerging therapies, Olezarsen (ASO anti-APOC3) and Plozasiran (siRNA anti-APOC3), both conjugated with GalNAc, show promise in reducing acute pancreatitis risk without platelet concerns. ANGPTL3 inhibition requires residual lipoprotein lipase (LPL) activity, with only siRNA-based therapies-zodasiran and solbinsiran-under investigation. Suppressing APOC3 expression and targeting ANGPTL3 via siRNA offer significant potential, but long-term studies are needed to confirm their efficacy and safety. Future research may explore gene-editing strategies using lipid nanoparticle-based CRISPR-Cas9 delivery for more durable treatment outcomes."

Journal • Review • Familial Chylomicronemia Syndrome • Hematological Disorders • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases • Thrombocytopenia • ANGPTL3 • APOC3 • LPL

EFFICACY AND SAFETY OF ANTISENSE OLIGONUCLEOTIDE THERAPIES TARGETING APOCIII IN PATIENTS WITH SEVERE HYPERTRIGLYCERIDEMIA: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS - Muhammad Ahmad Qureshi (ACC 2025) - "This meta-analysis confirms that ASOs Volanesorsen and Olezarsen effectively lower triglycerides and improve lipid profiles in severe HTG. Despite adverse effects, especially with Volanesorsen, these therapies may reduce the risk of acute pancreatitis compared to placebo. Overall, ASOs targeting APOC3 are valuable for managing HTG."

Retrospective data • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia • APOA1 • APOB • LPL

DIFFERENTIAL RESPONSES IN APOC-III AND TRIGLYCERIDE LOWERING IN FAMILIAL CHYLOMICRONEMIA SYNDROME DIAGNOSED BY GENETIC VERSUS NON-GENETIC CRITERIA - Sotirios Tsimikas (ACC 2025) - "For a similar reduction in apoC-III with volanesorsen, triglyceride reductions in patients with genetically diagnosed FCS are attenuated compared to those diagnosed by non-genetic criteria. These findings suggest patients with FCS identified genetically may represent a more severe phenotype of lipoprotein lipase deficiency."

Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • APOA5 • APOC3 • LPL

Renal Safety Assessment of Lipid-Lowering Drugs: Between Old Certainties and New Questions. (PubMed, Drugs) - "Conventional lipid-lowering therapies (LLTs), such as statins, ezetimibe, and fibrates, can control CKD-associated dyslipidemia and, to some extent, prevent major atherosclerotic events in patients with CKD, but their use in clinical practice presents challenges because of the potential renal safety concerns. In recent years, novel therapies with the ability to lower both low-density lipoprotein cholesterol and triglycerides have been introduced to the market (e.g., proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, lomitapide, volanesorsen) to improve our ability to control lipid abnormalities...The aim of this review was to examine the renal safety profiles of various LLTs, with special reference to novel medications, and to highlight important considerations and guidance for the use of these medications in overt CKD or in patients with some degree of renal function impairment. We underscore the lack of a comprehensive understanding of kidney..."

Journal • Review • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Dyslipidemia • Metabolic Disorders • Nephrology • Renal Disease

Safety and efficacy of antisense oligonucleotides on triglyceride, apolipoprotein C-III, and other lipid parameters levels in hypertriglyceridemia; a network meta-analysis of randomized controlled trials. (PubMed, Lipids Health Dis) - "APOC3 antisense oligonucleotide inhibitors effectively reduced triglyceride and APOC3 levels in hypertriglyceridemia with an acceptable safety profile. However, the results should be interpreted cautiously due to the small sample size. Further research is needed to confirm the beneficial effects of APOC3 inhibitors and show strong evidence of the impact of each regimen."

Clinical • Journal • Retrospective data • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • APOC3

Apolipoprotein C-III inhibitors for the treatment of hypertriglyceridemia: A meta-analysis of randomized controlled trials. (PubMed, Metabolism) - "APOC-III inhibitors improve TG levels and other lipid panel parameters, as well as reduce episodes of acute pancreatitis in patients with primary and secondary hypertriglyceridemia."

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

Targeting apolipoprotein C-III: a game changer for pancreatitis prevention in severe hypertriglyceridemia. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "SHTG is a high-burden metabolic disorder that is associated with a significantly increased incidence and severity of acute pancreatitis. Traditional lifestyle interventions and conventional therapies, including fibrates and n-3 fatty acids, often provide only modest reductions in triglycerides and fail to prevent sHTG-associated acute pancreatitis. The emergence of novel and targeted RNA-therapies represents a potential breakthrough in the management of sHTG and acute pancreatitis prevention."

Journal • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia

Current and Emerging Treatment Options for Hypertriglyceridemia: State-of-the-Art Review. (PubMed, Pharmaceuticals (Basel)) - "Among apolipoprotein C-III (apoC-III) inhibitors, olezarsen and plozasiran appear to be safer alternatives for volanesorsen regarding the risk of drug-induced thrombocytopenia in patients with FCS or severe HTG. After the failure of vupanorsen, a new angiopoietin-like protein 3 (ANGPTL3) inhibitor, zodasiran, demonstrated the potential to decrease TG levels in patients with moderate HTG. Meanwhile, the fibroblast growth factor 21 (FGF21) analog, pegozafermin, became another candidate for the treatment of severe HTG. This comprehensive review outlines pharmacological targets in TG-rich lipoprotein metabolism, discusses international guidelines, and summarizes the latest evidence from clinical trials to provide insight into the current and emerging treatment options for primary HTG."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia • ANGPTL3 • FGF21

Novel RNA-Based Therapies in the Management of Dyslipidemias. (PubMed, Int J Mol Sci) - "This article discusses the latest data from completed and ongoing trials on RNA therapies for dyslipidemia, including inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, and solbinsiran. Each therapy targets specific molecules while also significantly impacting other lipid parameters. The promising results of these trials indicate potential improvements in lipid therapy and cardiovascular risk reduction, with ongoing studies expected to further refine the role of the novel RNA-based agents in effective lipid management."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • ANGPTL3

Differential effects of volanesorsen on apoC-III, triglycerides and pancreatitis in familial chylomicronemia syndrome diagnosed by genetic or non-genetic criteria. (PubMed, J Clin Lipidol) - "For a similar reduction in apoC-III in response to volanesorsen, triglyceride reduction is attenuated in patients with genetically versus non-genetically diagnosed FCS."

Journal • Familial Chylomicronemia Syndrome • Pancreatitis • APOA5 • APOC3 • LPL