Tryngolza (olezarsen) / Ionis, Theratechnologies - LARVOL DELTA

Olezarsen and Post-prandial Triglyceride Levels. (PubMed, Eur J Prev Cardiol) - No abstract available

Journal

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

Ionis showcases transformational medicines and industry-leading pipeline at Innovation Day (Ionis Pharmaceuticals Press Release) - "Additionally, a leading physician will discuss the current treatment landscape and substantial unmet needs for severe hypertriglyceridemia (sHTG) in advance of the potential olezarsen launch."

Clinical data • Severe Hypertriglyceridemia

MTT.01: Meet the Trialists The CORE-TIMI 72a and CORE2-TIMI 72b Trials and DR10624, a First-In-Class, FGF21 Receptor/Glucagon Receptor/GLP-1 Receptor Triple Agonist (AHA 2025) - "Description: Meet the Trialists of Olezarsen in Patients with Severe Hypertriglyceridemia: The CORE-TIMI 72a and CORE2-TIMI 72b Trials and DR10624, a First-In-Class, FGF21 Receptor/Glucagon Receptor/GLP-1 Receptor Triple Agonist, Rapidly and Significantly Reduced Triglycerides, Atherogenic Lipids, and Liver Fat in Patients With Severe Hypertriglyceridemia: Primary Results From a Randomized Phase 2 Trial. Panelist: Nicholas A Marston (Brigham And Womens Hospital)"

Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia • FGF21

Olezarsen in Patients with Severe Hypertriglyceridemia: The CORE-TIMI 72a and CORE2-TIMI 72b Trials (AHA 2025) - "Available on Saturday, November 08, 2025 at 08:40am CDT."

Clinical • Late-breaking abstract • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

A Study of Olezarsen (ISIS 678354) Administered to Participants With Severe Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=617 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Trial primary completion date: Apr 2025 ➔ Oct 2024 | Active, not recruiting ➔ Completed

Trial completion • Trial primary completion date • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

A Study of Olezarsen Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=446 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed | Trial primary completion date: Jun 2025 ➔ Dec 2024

Trial completion • Trial primary completion date • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

Tryngolza (olezarsen) approved in the European Union for familial chylomicronemia syndrome (FCS) (Sobi Press Release) - "The approval follows the positive opinion of the Committee for Medicinal Products for Human Use. The approval is based on positive data from the Phase 3 Balance study..."

EMA approval • Familial Chylomicronemia Syndrome

Olezarsen significantly reduces triglycerides and acute pancreatitis events in landmark pivotal studies for people with severe hypertriglyceridemia (sHTG) (Yahoo Finance) - "In the studies, olezarsen demonstrated a highly statistically significant placebo-adjusted mean reduction in fasting triglycerides of up to 72% and a highly statistically significant reduction in acute pancreatitis events of 85% with favorable safety and tolerability....Ionis plans to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration by end of year. Detailed data will be presented at an upcoming medical conference."

FDA filing • P3 data: top line • Severe Hypertriglyceridemia

ESSENCE-TIMI 73b: Olezarsen Normalizes TGs in 80% of Patients With HTG (HCPLive) - "Primary results of the trial suggested the placebo-adjusted least-squares mean change in TG level was −58.4 percentage points (95% confidence interval [CI], −65.1 to −51.7; P <.001) in the olezarsen 50 mg group and −60.6 percentage points (95% CI, −67.1 to −54.0; P <.001) in the olezarsen 80 mg group. The least-squares mean change from baseline in triglyceride level was −55.6% (95% CI, −58.0 to −53.2) in the olezarsen 50 mg group, −57.8% (95% CI, −59.6 to −55.9) in the olezarsen 80 mg group, and 2.8% (95% CI, −3.5 to 9.0) in the placebo group."

P3 data • Severe Hypertriglyceridemia

Targeting APOC3 with Olezarsen in Moderate Hypertriglyceridemia. (PubMed, N Engl J Med) - P3 | "Among patients with moderate hypertriglyceridemia and elevated cardiovascular risk, treatment with olezarsen resulted in significantly greater reduction in triglyceride levels at 6 months than placebo. (Funded by Ionis Pharmaceuticals; ESSENCE-TIMI 73b ClinicalTrials.gov number, NCT05610280.)."

Journal • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

Olezarsen in patients with hypertriglyceridemia at high cardiovascular risk: the Essence-TIMI 73b trial (ESC-WCC 2025) - No abstract available

Clinical • Cardiovascular • Dyslipidemia

Olezarsen: “The committee was reminded of the status of this application and its remaining outstanding issues”; Familial chylomicronemia syndrome (European Medicines Agency) - CHMP Final Minutes of the meeting on 19 - 22 May 2025: “The committee adopted a list of outstanding issues with a specific timetable”

CHMP • Familial Chylomicronemia Syndrome • Metabolic Disorders

Brief communication: Strong concordance of the North American Familial Chylomicronemia Syndrome Score with a positive genetic diagnosis in patients from the Balance study. (PubMed, J Clin Lipidol) - "The strong concordance between NAFCS Score ≥45 and a positive genetic diagnosis of FCS suggests that either approach can be used for diagnosis except in "uncertain FCS" cases, which require genetic testing. The score might also clinically support an FCS diagnosis when genetic testing is indeterminate due to variants of unknown significance."

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

Ionis reports second quarter 2025 financial results and highlights progress on key programs (Businesswire) - "TRYNGOLZA (olezarsen): Generated net product sales of $19 million in the second quarter of 2025, its second full quarter on the market, and $26 million in the first half of 2025...Olezarsen on track for topline Phase 3 data from pivotal CORE and CORE2 studies in patients with sHTG in September 2025, positioning olezarsen to potentially treat this second, more prevalent patient population with high unmet need....Donidalorsen on track to launch this year, assuming approval, with a U.S. PDUFA date of August 21, 2025. Poised to transform the treatment paradigm for individuals with hereditary angioedema (HAE) as the first and only RNA-targeted prophylactic therapy that has the potential to offer durable efficacy, a favorable safety and tolerability profile, and the longest available dosing interval, with self-administration via autoinjector monthly or every other month."

Launch US • P3 data: top line • PDUFA • Sales • Familial Chylomicronemia Syndrome • Hereditary Angioedema • Severe Hypertriglyceridemia

Patient experience with familial chylomicronemia syndrome before and after olezarsen treatment: Qualitative interviews with clinical trial participants. (PubMed, J Clin Lipidol) - P3 | "Results of this qualitative study underscore the significant burden of FCS and support the effectiveness of olezarsen from the patient perspective."

Interview • Journal • Familial Chylomicronemia Syndrome • Fatigue • Genetic Disorders • Pain • Pancreatitis

The impact of olezarsen on hypertriglyceridemia in high cardiovascular risk patients: a systematic review, meta-analysis, and meta-regression. (PubMed, Ann Med Surg (Lond)) - "Although serious adverse events were more frequent, the overall safety profile remains acceptable. Further long-term research is required to validate these findings and optimize treatment regimens."

Journal • Retrospective data • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • APOA1 • APOB • APOC3

Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 21-24 July 2025 (European Medicines Agency) - "On 24 July 2025, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for the medicinal product Tryngolza, intended for the treatment of adults with familial chylomicronemia syndrome (FCS)."

CHMP • Familial Chylomicronemia Syndrome

A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=1478 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia • APOB

Plasma reduction of apolipoprotein C-III with olezarsen leads to significant reductions in postprandial triglyceride levels: Results from a randomized trial. (PubMed, Eur J Prev Cardiol) - "Olezarsen significantly reduces both fasting and postprandial triglyceride levels, these findings highlight olezarsen as a promising intervention to managing hypertriglyceridemia and reducing the risk of hypertriglyceridemia induced acute pancreatitis."

Journal • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Pancreatitis

Effect of olezarsen on lipoprotein-associated ApoC-III levels in patients with familial chylomicronemia syndrome. (PubMed, Atherosclerosis) - "In adults with FCS, olezarsen significantly lowers apoC-III in all major lipoprotein pools, particularly in total apoB and apoA-I. Tracking changes in apoC-III among various lipoprotein pools elucidates the action of olezarsen on apoC-III and may inform future studies of pancreatitis and cardiovascular risk with apoC-III-targeted therapies."

Journal • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Pancreatitis • APOB

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

Targeting Triglycerides: The Rise of Apolipoprotein C3 and Angiopoietin-Like Protein 3 Inhibitors. (PubMed, Am J Cardiovasc Drugs) - "Several novel agents utilizing these pathways, including olezarsen, plozasiran, and zodasiran, are currently under development for the management of elevated TG, with olezarsen approved in 2024 for the management of familial chylomicronemia syndrome. This comprehensive review provides updated insights into the development of novel hypertriglyceridemia treatments."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • ANGPTL3

Optimizing cardiovascular health: a systematic review and meta-analysis of olezarsen dosages in high-risk hypertriglyceridemic patients. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Olezarsen effectively improves key lipid parameters, including TG, VLDL-C, ApoB, non-HDL-C, and LDL-C, while also safely raising HDL-C in patients with high-risk hypertriglyceridemia. Total cholesterol remained stable, and no increase in adverse events was noted. Further studies are needed to determine optimal dosing and long-term cardiovascular benefits."

Journal • Retrospective data • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • APOB

Effect of olezarsen on routinely measured lipase and amylase levels in familial chylomicronemia syndrome. (PubMed, J Clin Lipidol) - "Changes in routinely measured lipase levels may reflect subclinical pancreatic injury. Olezarsen favorably modifies changes in lipase in patients with FCS."

Journal • Familial Chylomicronemia Syndrome • Pain • Pancreatitis