Tryngolza (olezarsen) / Ionis, Theratechnologies - LARVOL DELTA

Molecular Therapeutics in Development to Treat Hyperlipoproteinemia. (PubMed, Mol Diagn Ther) - "Inhibition of APOC3 messenger RNA expression by olezarsen and plozasiran significantly lowers plasma triglyceride levels and markedly reduces pancreatitis risk in patients with familial chylomicronemia syndrome. Finally, angiopoietin-like protein 3 inhibition by the monoclonal antibody evinacumab has transformed management of patients with homozygous familial hypercholesterolemia. Together, these novel agents expand the therapeutic cache, offering personalized lipid-lowering strategies for high-risk patients with hyperlipoproteinemia, improving clinical outcomes and addressing previously unmet medical needs."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Pancreatitis

OLEZARSEN REDUCES ALL-CAUSE HEALTHCARE UTILIZATION IN PATIENTS WITH FAMILIAL CHYLOMICRONEMIA SYNDROME - Asia Sikora Kessler (ACC 2025) - No abstract available

Clinical • HEOR • Familial Chylomicronemia Syndrome

EFFECT OF OLEZARSEN ON LIPOPROTEIN-ASSOCIATED APOC-III IN PATIENTS WITH FAMILIAL CHYLOMICRONEMIA SYNDROME - Sotirios Tsimikas (ACC 2025) - No abstract available

Clinical • Familial Chylomicronemia Syndrome

OLEZARSEN REDUCES LIPOPROTEIN(A)-ASSOCIATED TRIGLYCERIDE CONTENT IN PATIENTS WITH MODERATE HYPERTRIGLYCERIDEMIA - Sotirios Tsimikas (ACC 2025) - No abstract available

Clinical • Dyslipidemia • Hypertriglyceridemia

EFFECT OF OLEZARSEN IN PATIENTS WITH HYPERTRIGLYCERIDEMIA-A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS - Ameer Haider Cheema (ACC 2025) - No abstract available

Retrospective data • Dyslipidemia • Hypertriglyceridemia

Exploring emerging pharmacotherapies for type 2 diabetes patients with hypertriglyceridemia. (PubMed, Expert Opin Pharmacother) - "These were identified by a PubMed search and mainly focus on pemafibrate and the drugs targeting apolipoprotein C3 (apoC3) and angiopoietin-like 3 (ANGPTL3)...Inhibitors of apoC3 are effective in reducing triglycerides even in familial chylomicronaemia syndrome and olezarsen and plozasiran in this group are being studied in patients with combined hyperlipidemia. The ANGPTL3 inhibitor evinacumab has been approved for homozygous familial hypercholesterolemia and other ANGPTL3 inhibitors may prove be useful to reduce triglycerides in T2D."

Journal • Review • Cardiovascular • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus • ANGPTL3

Ionis enters new chapter in 2025 as commercial-stage biotech with multiple independent product launches anticipated and continued late-stage pipeline momentum (PRNewswire) - "2025 Anticipated Highlights Include: Phase 3 results and U.S. regulatory submission for olezarsen in severe hypertriglyceridemia, a large patient population with high unmet need: Phase 3 topline data for CORE, CORE 2 and ESSENCE Phase 3 trials expected in second half of 2025; Potential approval of donidalorsen, a first-in-class RNA-targeted medicine for hereditary angioedema and Ionis' second anticipated independent launch: U.S. FDA action date of August 21, 2025 U.S. commercial field team scale-up and launch."

Filing • Launch • P3 data • PDUFA • Hereditary Angioedema • Severe Hypertriglyceridemia

FDA Approves Ionis Pharmaceuticals’ Rare Genetic Disease Therapy to Lower High-Level Of Fat In Blood (Yahoo Finance) - "...the FDA approved Ionis Pharmaceuticals, Inc.’s...Tryngolza (olezarsen) as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS), a rare, genetic form of severe hypertriglyceridemia (SHTG) that can lead to acute pancreatitis (AP)....The FDA approval was based on Phase 3 Balance trial data in adult patients. In the Balance study, Tryngolza 80 mg demonstrated a statistically significant placebo-adjusted mean reduction in triglyceride levels of 42.5% from baseline to six months (p=0.0084)."

FDA approval • Familial Chylomicronemia Syndrome • Metabolic Disorders

PANTHERx Rare Selected by Ionis as Specialty Pharmacy for TRYNGOLZA (olezarsen) (PRNewswire) - "PANTHERx Rare...is pleased to announce that it was selected by Ionis Pharmaceuticals, Inc. for the distribution of TRYNGOLZA (olezarsen), the first and only treatment approved by the U.S. Food and Drug Administration (FDA) as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS)."

Commercial • Familial Chylomicronemia Syndrome

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

An up-to-date review of emerging biologic therapies for hypercholesterolemia. (PubMed, Expert Opin Biol Ther) - "In addition to the currently available monoclonal antibodies (mAbs) and small interfering RNA (siRNA), new mAbs and the adenectin lerodalcibep are promising therapies. The antisense oligonucleotide (ASO) and siRNA inhibitors of apoC3 and ANGPTL3 are effective in severe hypertriglyceridemia and homozygous familial hypercholesterolemia, respectively, and may prove to have wider applications. ASO and siRNA inhibitors of Lp(a) are currently in cardiovascular outcome studies."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • 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

Theratechnologies Announces Exclusive Licensing Agreement with Ionis to Commercialize Olezarsen and Donidalorsen in Canada (GlobeNewswire) - "Theratechnologies Inc...today announced it has entered into an agreement with Ionis Pharmaceuticals, Inc. (Ionis) to license two investigational RNA-targeted medicines developed by Ionis. Under the agreement, Theratechnologies receives exclusive rights in Canada for olezarsen, which is being evaluated for familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (sHTG), and for donidalorsen, which is being evaluated for the treatment of hereditary angioedema (HAE). All figures are in U.S. dollars unless otherwise stated."

Licensing / partnership • Familial Chylomicronemia Syndrome • Hereditary Angioedema • Severe Hypertriglyceridemia

Response to the letter to the editor: 'olezarsen, a liver-directed APOC3 ASO therapy for hypertriglyceridemia'. (PubMed, Expert Opin Pharmacother) - No abstract available

Journal • Dyslipidemia • Hypertriglyceridemia

Letter to the Editor - 'olezarsen, a liver-directed APOC3 ASO therapy for hypertriglyceridemia'. (PubMed, Expert Opin Pharmacother) - No abstract available

Journal • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Thrombocytopenia

Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk - A Systematic Review and Meta Analysis (AHA 2024) - "Olezarsen demonstrates significant efficacy in reducing triglyceride and VLDL levels while improving overall lipid profiles in hypertriglyceridemia patients. Despite higher rates of serious adverse events, its overall safety profile remains acceptable."

Retrospective data • Review • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • APOA1 • APOB

Assessing the Efficacy and Safety of Olezarsen in Lowering Triglyceride Levels: A Systematic Review and Meta-Analysis (AHA 2024) - "A significant reduction was noted in TG, apoC-III, apo-B48, and non-HDLC levels, indicating a significant effect of olezarsen on these parameters. Additionally, olezarsen exhibited no significant side effects, making this medication comparatively safe. More research may be warranted to validate these findings and explore the drug's impact on cardiovascular outcomes."

Retrospective data • Review • Cardiovascular • Dyslipidemia • Hypertriglyceridemia

Efficacy and safety of olezarsen in lowering apolipoprotein C-III and triglycerides in healthy Japanese Americans. (PubMed, Lipids Health Dis) - "Single- and multiple-dose administration of olezarsen was safe, was well tolerated, and significantly reduced apoC-III and triglyceride levels in healthy Japanese Americans."

Clinical • Journal • Cardiovascular • Pancreatitis • APOB

Olezarsen and Plozasiran in Dyslipidemia Management: A Narrative Review of Clinical Trials. (PubMed, High Blood Press Cardiovasc Prev) - "The review discusses the therapeutic effects of Olezarsen and Plozasiran in managing dyslipidemia, especially familial chylomicronemia syndrome (FCS). While traditional treatments like lifestyle modifications and statins are common, novel antisense oligonucleotides such as Olezarsen and Plozasiran have significant modulatory effects on apolipoproteins, disrupting specific genes involved in lipid metabolism."

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

Olezarsen for the treatment of hypertriglyceridemia and familial chylomicronemia syndrome (PubMed, Inn Med (Heidelb)) - No abstract available

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia

Olezarsen, a liver-directed APOC3 ASO therapy for hypertriglyceridemia. (PubMed, Expert Opin Pharmacother) - "The need for 4-weekly administration puts olezarsen at a disadvantage to competing injectables. Results from the CORE, CORE2, and ESSENCE phase III clinical trials in patients with severe HTG, expected in the second half of 2025, will help determine the requirement for a larger cardiovascular outcomes trial."

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

Safety and efficacy of the novel RNA interference therapies for hypertriglyceridemia and mixed hyperlipidemia management: a systematic review and meta-analysis. (PubMed, Endocr Pract) - "The newer RNA interference (RNAi) therapies appear safe and have excellent TG-lowering efficacy in patients with HTG and MHL."

Journal • Retrospective data • Review • Diabetes • Dyslipidemia • Hypertriglyceridemia • Mixed Hyperlipidemia • APOB

The Risk Of Arteriosclerosis And Its Complications Are Increased By LDL Cholesterol (LDL-C) Levels, Elevated Lp(a) And Inflammation: What Are The Best Medical Strategies To Decrease These Parameters: Statins, Adjunctive LDL-C Lowering Drugs Inclisiran, Bempedoic Acid, Ezetimibe, PCSK-9 Inhibitors, Lepodisiran, Colchicine, Olezarsen, Etc.) And Anti-Inflammatories: How They Should Be Administered (VEITH 2024) - No abstract available

Atherosclerosis • Cardiovascular • Inflammation

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