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

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

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

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

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

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

SEVERELY ELEVATED TRIGLYCERIDES ABOVE 7000- A CASE REPORT AND MINIATURE REVIEW OF FAMILIAL HYPERTRIGLYCERIDEMIA. (WRMC 2025) - "FCS is not responsive to traditional fibrate therapies; however limited treatments targeting FCS such as volanesorsen are available in the EU, thus testing can be beneficial in some scenarios. Given the risks and cost associated with genetic testing, more research is indicated in this area to help streamline clinical guidelines and prevent the over-utilization of this resource."

Case report • Clinical • Review • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders • Obesity • Pancreatitis • Severe Hypertriglyceridemia • APOA5 • APOE

Familial chylomicronemia: New perspectives. (PubMed, Clin Investig Arterioscler) - "ApoCIII antagonists, specifically volanesorsen, olezarsen and ARO-APOC3, are the most promising drugs to reduce TG concentrations in patients with FCS. Anti-ANGPTL3 therapies appear to be less effective. More clinical trials and new pharmacological treatments are needed to improve the quality of life and prognosis of people with FCS."

Journal • Review • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Metabolic Disorders • Pain • Pancreatitis • Severe Hypertriglyceridemia • ANGPTL3

Safety and Efficacy of Antisense Oligonucleotides On Triglyceride and Apolipoprotein C-III Levels in Hypertriglyceridemia; A Network Meta-Analysis Of Randomized Controlled Trials (AHA 2024) - "Apolipoprotein C-III (APOC3) inhibition through the antisense oligonucleotides volanesorsen, olezarsen, and plozasiran, reduced triglycerides in the previous trials. However, due to the relatively small sample size, the results should be interpreted with caution. Further research is needed to confirm the beneficial effects of APOC3 inhibitors and provide strong evidence on the effects of each medication regimen."

Retrospective data • Dyslipidemia • Hypertriglyceridemia • APOC3

A Study of Olezarsen (Formerly Known as AKCEA-APOCIII-LRX) Administered to Adults With Familial Chylomicronemia Syndrome (FCS) Previously Treated With Volanesorsen (clinicaltrials.gov) - P3 | N=24 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial completion date: Jun 2025 ➔ Jun 2027 | Trial primary completion date: Mar 2025 ➔ Jun 2027

Trial completion date • Trial primary completion date • Familial Chylomicronemia Syndrome

A drug target Mendelian randomization study of triglyceride lowering therapies for aortic stenosis (AHA 2024) - "Next, we identified genetic proxies for the TG-lowering therapies fenofibrate, volanesorsen and evinacumab as single nucleotide polymorphisms (SNPs) within 200kb of the target genes (PPARA, APOC3 and ANGPTL3, respectively) which were also significantly associated with TG at p<5x10-8 and clumped using threshold r2<0.1. Genetically proxied APOC3 inhibition, but not PPARA or ANGPTL3, was robustly associated with reduced risk of AS. This suggests that APOC3 inhibition may be a therapeutic opportunity for AS management and warrants further research in the clinical trial setting."

Hypertriglyceridemia • ANGPTL3 • PPARA

Exploring volanesorsen: a promising approach to preventing acute pancreatitis in severe hypertriglyceridemia. (PubMed, Ann Transl Med) - No abstract available

Journal • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

Antisense Oligonucleotides in Dyslipidemia Management: A Review of Clinical Trials. (PubMed, High Blood Press Cardiovasc Prev) - "The potential of antisense oligonucleotides (ASOs) to treat dyslipidemia and other disorders has attracted much interest. Several studies and clinical trials have been conducted on the safety and tolerability of ASOs for dyslipidemia. Although statins are the mainstay management of hypercholesterolemia, there is evidence from clinical trials that ASOs can even be more effective with little to no side effects. Novel therapeutic approaches such as antisense oligonucleotides (ASOs) offer tailored therapeutic alternatives. ASOs such as Mipomersen and Volanesorsen provide additional treatment options for patients with inherited lipid abnormalities by lowering certain atherogenic lipoproteins such as apo B and ApoC-III, respectively."

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

Assessment of Platelet Aggregation and Thrombin Generation in Patients with Familial Chylomicronemia Syndrome Treated with Volanesorsen: A Cross-Sectional Study. (PubMed, Biomedicines) - "Our study showed for the first time that no significant changes in general hemostasis assessed by TG and in platelet function were observed in FCS patients receiving volanesorsen."

Journal • Observational data • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Severe Hypertriglyceridemia

Expanding therapeutic options: overview of novel pharmacotherapies for dyslipidemia. (PubMed, Expert Opin Pharmacother) - "Optimizing the use of available first- and second-line lipid-lowering drugs allows us to adequately control low-density lipoprotein cholesterol (LDL-C) levels, even in statin-intolerant individuals and in patients at high and very high risk of developing cardiovascular diseases who must reach more aggressive LDL-C targets. The drugs under development will further improve our ability to manage the overall lipid-related cardiovascular disease risk and target other dyslipidemia biomarkers."

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

Targeting Apolipoprotein C-III for the Management of Severe Hypertriglyceridemia: Current Research and Future Directions. (PubMed, Cureus) - "Antisense oligonucleotides like volanesorsen have displayed effectiveness in lowering triglyceride levels in individuals with severe hypertriglyceridemia. This review article delves into how APOC3 influences triglyceride control and its potential use in targeting APOC3 to manage severe hypertriglyceridemia."

Journal • Review • Cardiovascular • Diabetes • Dyslipidemia • Gastrointestinal Disorder • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • APOC3

BREAKING THE CHAINS OF LIPOPROTEIN LIPASE DEFICIENCY: A PEDIATRIC PERSPECTIVE ON THE EFFICACY AND SAFETY OF VOLANESORSEN (SSIEM 2024) - "This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population."

Clinical • Dyslipidemia • Metabolic Disorders • Pain • Pancreatitis • Pediatrics • LPL

VOLANESORSEN IN PATIENTS WITH MONOGENIC HYPERTRIGLYCERIDEMIA. REAL LIFE DATA (SSIEM 2024) - "Volanesorsen is an effective treatment for pancreatitis prevention in FCS, however side effects including thrombocytopenia and allergic reactions remain a significant limiting factor for its use in many patients."

Clinical • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Thrombocytopenia • APOA5

Transition of patients with familial chylomicronaemia syndrome from volanesorsen to olezarsen: safety and pharmacokinetic results (ESC 2024) - "Conclusions. In this interim analysis, olezarsen was safe and well tolerated in pts with FCS previously treated with volanesorsen after a minimum washout of 6 weeks."

Clinical • PK/PD data • Cardiovascular • Dyslipidemia • LPL

Two successful pregnancies -in patients taking Volanesorsen for familial chylomicronemia syndrome. (PubMed, JIMD Rep) - "In both case, fetal health was maintained throughout pregnancy, fetal scans revealed no anomalies, and planned C-sections delivered healthy babies without congenital issues. Both babies are well and developing normally at 24 and 19 months."

Journal • Dyslipidemia • Genetic Disorders • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Thrombocytopenia

Repurposing lipid-lowering drugs on asthma and lung function: evidence from a genetic association analysis. (PubMed, J Transl Med) - "In conclusion, our findings suggest a likely causal relationship between asthma and lipid-lowering drugs. Moreover, there is compelling evidence indicating that lipid-lowering therapies could play a crucial role in the future management of asthma."

Journal • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • ANGPTL3 • APOB • LDLR • PPARA