Tryngolza (olezarsen) / Ionis, Future Pak, SOBI - LARVOL DELTA

The UK's National Institute for Health and Care Excellence (NICE) has issued final draft guidance recommending Tryngolza (olezarsen)…to treat genetically confirmed familial chylomicronaemia syndrome (FCS) in adults in England and Wales whose response to diet and conventional triglyceride-lowering treatments, such as statins and fibrates, has been inadequate (The Pharma Letter)

NICE • Familial Chylomicronemia Syndrome

Development of Antisense Oligonucleotide Gapmers for the Treatment of Dyslipidemia and Lipodystrophy. (PubMed, Methods Mol Biol) - "Mipomersen (trade name Kynamro), a 2'-O-methoxyethyl (MOE) gapmer, was approved by the Food and Drug Administration (FDA) for the treatment of homozygous familial hypercholesterolemia (HoFH) in 2013. Volanesorsen, another 20-mer MOE gapmer, has shown to be successful in lowering the levels of triglycerides (TGs) in several lipid disorders and has received conditional approval in the European Union for the treatment of familial chylomicronemia syndrome (FCS) in May 2019 following successful results from phase II/III clinical trials. This chapter focuses on the clinical applications of gapmer AOs for general dyslipidemia and lipodystrophy."

Journal • Review • Cardiovascular • CNS Disorders • Duchenne Muscular Dystrophy • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Lipodystrophy • Metabolic Disorders • Movement Disorders • Muscular Atrophy • Muscular Dystrophy • Rare Diseases

Olezarsen for the Treatment of Hypertriglyceridemia. (PubMed, Methods Mol Biol) - "Olezarsen, a next-generation N-acetylgalactosamine-conjugated antisense oligonucleotide (ASO) designed to induce RNase H-mediated degradation of APOC3 mRNA, received FDA approval in December 2024 as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). In this chapter, we review the pharmacological mechanism, clinical development, and safety profile of olezarsen for FCS and broader hypertriglyceridemia-related indications."

Journal • Review • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Metabolic Disorders

OLEZARSEN REDUCES THE RISK OF ACUTE PANCREATITIS AND IMPROVES LIPID PROFILES IN SEVERE HYPERTRIGLYCERIDEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS (UEGW 2026) - "Olezarsen demonstrates robust efficacy in reducing acute pancreatitis risk and improving lipid profiles in severe hypertriglyceridemia, with an acceptable safety profile. These findings support olezarsen as a promising therapeutic option for this high-risk population."

Retrospective data • Review • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia

Efficacy and Safety of Olezarsen in High-Risk Hypertriglyceridemic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials With Dose-Response and Obesity Subgroup Analyses (ACG 2026) - "Six randomized trials involving over 2,000 participants were included. Olezarsen significantly reduced triglycerides compared with placebo (MD = â30.54%, 95% CI â38.59 to â22.49; p< 0.00001). In obesity subgroup analyses, triglycerides decreased by â74.18% (95% CI â106.77 to â41.60) in obese patients and â43.80% (95% CI â70.10 to â17.50) in non-obese patients, without significant interaction (p=0.16)."

Retrospective data • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Gastrointestinal Disorder • Genetic Disorders • Hypertriglyceridemia • Obesity • Pancreatitis • Severe Hypertriglyceridemia • APOB

Efficacy and Safety of Olezarsen in Severe Hypertriglyceridemia and Pancreatitis Prevention: A Systematic Review and Meta-Analysis (ACG 2026) - "Five trials comprising 953 patients were included. Olezarsen demonstrated profound, dose-dependent reductions in lipids. At 6 months, apoC-III levels decreased significantly with the 50 mg (SMD: -9.39; 95% CI: -12.36, -6.43) and 80 mg doses (SMD: -7.10; 95% CI: -9.77, -4.44) versus placebo."

Retrospective data • Review • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • APOC3

A Novel Triglyceride- and Cholesterol-Enriched Lipoprotein(a) Phenotype in Moderate Hypertriglyceridemia: Reversal by ApoC-III Inhibition. (PubMed, JACC Basic Transl Sci) - P2 | "These findings identify Lp(a) lipid composition as a dynamic, therapeutically modifiable feature in hypertriglyceridemia. (Study of ISIS 678354 [AKCEA-APOCIII-LRx] in Participants With Hypertriglyceridemia and Established Cardiovascular Disease [CVD]; NCT03385239)."

Journal • Cardiovascular • Dyslipidemia • Hypertriglyceridemia

Dose-dependent Efficacy And Safety Of Olezarsen, An Antisense Oligonucleotide, In Hypertriglyceridemia: A Network Meta-analysis And Bayesian Meta-regression Of Randomized Clinical Trials. [Poster no. 220] (HFSA 2026) - No abstract available

Retrospective data • Dyslipidemia • Hypertriglyceridemia

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

Dose-related effects of olezarsen in hypertriglyceridaemia: a systematic review and meta-analysis of 2,610 patients (ESC 2026) - "At 12 months, olezarsen produced robust reductions in triglycerides and TRL-related biomarkers, with consistent improvements in ApoC-III and remnant cholesterol across both doses. Clinically, dose selection should be guided by safety: 80 mg was associated with increased thrombocytopenia, whereas 50 mg maintained substantial lipid efficacy and was associated with a lower risk of >25% eGFR decline. These findings support phenotype-guided individualised dosing and underscore the need for longer, adequately powered trials to determine cardiovascular and renal outcomes."

Retrospective data • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • APOB

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

Long-term efficacy and safety of olezarsen in patients with severe hypertriglyceridemia (ESC 2026) - "ALT>3x ULN occurred in 2.4% and >5x ULN in 0.5%, platelet counts <100K in 2.4% and <75K in 0.9%. Conclusions Long-term olezarsen treatment resulted in clinically meaningful, durable reductions in TG with low rates of adverse events."

Clinical • Cardiovascular • Dyslipidemia

Efficacy and safety of olezarsen in patients with vs without baseline fibrate use. (PubMed, J Clin Lipidol) - "Olezarsen reduced triglycerides across the hypertriglyceridemia spectrum, with greater effects in patients on background fibrates, particularly with diabetes. Findings support potential complementary mechanisms and further investigation of concomitant triglyceride-reducing therapy."

Clinical • Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • APOC3 • LPL

Dose-related effects of olezarsen on HbA1c and insulin homeostasis by diabetes status: a systematic review and meta-analysis (ESC 2026) - "At 12 months, olezarsen was associated with modest, phenotype- and dose-dependent glycaemic and insulin homeostasis signals in moderate and severe hypertriglyceridaemia. In type 2 diabetes, 50 mg increased HbA1c, while 80 mg was not statistically different for HbA1c or HOMA-IR but was associated with lower HOMA-B. In participants without diabetes, HbA1c increased with 80 mg, whereas insulin resistance increased with 50 mg; neither dose produced consistent changes in HOMA-B."

Retrospective data • Review • Cardiovascular • Dyslipidemia

Olezarsen (Tryngolza) for severe hypertriglyceridemia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

ApoC-III Antisense Oligonucleotide Therapy Used in Glycogen Storage Disease Type 1a. (PubMed, JACC Case Rep) - "GSD1a-driven hypertriglyceridemia may be treatable using apoCIII-ASO."

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

CELYSTRA Pharma today announced that Québec has become the first Canadian province to provide public coverage for TRYNGOLZA (olezarsen), the first treatment approved by Health Canada for familial chylomicronemia syndrome (FCS), a rare genetic disease (Canada Newswire) - "TRYNGOLZA is listed on the Régie de l'assurance maladie du Québec (RAMQ) List of Medications for eligible patients, in accordance with the applicable coverage criteria."

Reimbursement • Familial Chylomicronemia Syndrome

Recent Highlights - Wholly Owned Medicines: TRYNGOLZA (Ionis Pharmaceuticals Press Release) - "FCS launch outside the U.S. underway; sHTG marketing application under review in the European Union (EU) with potential launch in 2027; Results from the CORE and CORE2 open-label extension study (CORE-OLE) will be presented at the European Society of Cardiology (ESC) Congress in August 2026."

Launch Europe • P3 data • Familial Chylomicronemia Syndrome • Severe Hypertriglyceridemia

Ionis reports second quarter 2026 financial results… (Ionis Pharmaceuticals Press Release) - "TRYNGOLZA (olezarsen), the first FDA-approved treatment to reduce triglycerides and acute pancreatitis risk in adults with severe hypertriglyceridemia (sHTG) as an adjunct to diet: Generated U.S. net product sales of $5 million and $32 million in the second quarter and first half of 2026, respectively; Demonstrated continued strong demand in FCS, offset by the reduced net price effective April 1, 2026; On track to achieve full year 2026 product sales of $100-110 million, in line with revenues generated in 2025."

Sales • Sales projection • Familial Chylomicronemia Syndrome • Severe Hypertriglyceridemia

A Study of Olezarsen for the Treatment of Familial Chylomicronemia Syndrome (FCS) in Pediatric Participants (clinicaltrials.gov) - P3 | N=12 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc.

New P3 trial • Familial Chylomicronemia Syndrome • Pediatrics

Drugs for hypertriglyceridemia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Dyslipidemia • Hypertriglyceridemia

Olezarsen and Plozasiran: Novel apoC-III targeting medications for the treatment of hypertriglyceridemia. (PubMed, J Cardiovasc Pharmacol) - "Overall, both agents appear generally well tolerated, although monitoring of liver enzymes and glycemic control is warranted for both agents, and additional monitoring of platelet counts for olezarsen. Future clinical trials are needed to assess whether the TG-lowering effects of each agent are associated with reduced risk of pancreatitis and ASCVD events."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Pancreatitis

Extreme Hypertriglyceridemia >10,000 mg/dL With Mild Clinical Presentation: A Case Report (ENDO 2026) - "History revealed multiple contributing factors, including discontinuation of insulin glargine one month prior and metformin one week prior, along with cessation of atorvastatin 20 mg daily six months earlier due to persistent myalgias attributed to fibromyalgia. She was also receiving tirzepatide, with recent exposure to antipsychotic therapy and norethindrone...She was initiated on rosuvastatin 40 mg daily, fenofibrate 145 mg daily, and prescription-strength omega-3 fatty acids, with plans for outpatient initiation of olezarsen. Extreme hypertriglyceridemia can present with a clinically mild and rapidly resolving course. This case emphasizes the disconnect between triglyceride levels and clinical severity and supports the effectiveness of conservative management with dietary modification and insulin therapy."

Case report • Clinical • Late-breaking abstract • CNS Disorders • Diabetes • Dyslipidemia • Fibromyalgia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Musculoskeletal Pain • Pancreatitis • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus

Acute Pancreatitis Revealing Familial Chylomicronemia Syndrome in a Complex Metabolic Setting (ENDO 2026) - "Medication review demonstrated inconsistent adherence to metformin, glipizide, empagliflozin/metformin XR, fenofibrate, and incretin-based therapy. While no causal relationship can be established, the coexistence of severe genetic dyslipidemia and incretin-based therapy illustrates the clinical complexity encountered in high-risk metabolic phenotypes and underscores the need for individualized therapeutic assessment and close monitoring. Early diagnosis of FCS and timely initiation of emerging RNA-targeted therapies, such as olezarsen, are critical to preventing recurrent pancreatitis and improving long-term outcomes."

Asthma • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertension • Hypertriglyceridemia • Immunology • Metabolic Disorders • Obesity • Pancreatitis • Respiratory Diseases • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus • APOA5

Acute Pancreatitis Revealing Familial Chylomicronemia Syndrome in a Complex Metabolic Setting (ENDO 2026) - "Medication review demonstrated inconsistent adherence to metformin, glipizide, empagliflozin/metformin XR, fenofibrate, and incretin-based therapy. While no causal relationship can be established, the coexistence of severe genetic dyslipidemia and incretin-based therapy illustrates the clinical complexity encountered in high-risk metabolic phenotypes and underscores the need for individualized therapeutic assessment and close monitoring. Early diagnosis of FCS and timely initiation of emerging RNA-targeted therapies, such as olezarsen, are critical to preventing recurrent pancreatitis and improving long-term outcomes."

Asthma • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertension • Hypertriglyceridemia • Immunology • Metabolic Disorders • Obesity • Pancreatitis • Respiratory Diseases • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus • APOA5