Tryngolza (olezarsen) / Ionis, Theratechnologies, SOBI - LARVOL DELTA

Ionis receives U.S. FDA Breakthrough Therapy designation for olezarsen for severe hypertriglyceridemia (sHTG) (Businesswire) - "The Breakthrough Therapy designation is based on results from the Phase 3 CORE and CORE2 studies of olezarsen...Ionis is on track to submit a supplemental new drug application to the U.S. FDA by the end of the year."

Breakthrough therapy • FDA filing • Severe Hypertriglyceridemia

CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG) (clinicaltrials.gov) - P3 | N=885 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

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

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. This is not a CE accredited session. Panelist: Nicholas A Marston (Brigham And Womens Hospital)"

Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia • FGF21

Olezarsen in moderate hypertriglyceridemia: The Essence-TIMI 73b trial. (PubMed, Med) - "The Essence-TIMI 73b trial demonstrated that monthly injections of olezarsen, an antisense oligonucleotide targeting hepatic APOC3, over 6 months increased HDL cholesterol and significantly decreased the concentrations of triglycerides, apolipoprotein C-III, apolipoprotein B, non-HDL-C, VLDL cholesterol, and remnant cholesterol in adults with moderate hypertriglyceridemia.1 Studies assessing the long-term safety of olezarsen are ongoing. Whether olezarsen decreases cardiovascular outcomes remains undetermined."

Journal • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • APOB

Healthcare Resource Utilization Associated With Acute Pancreatitis in Patients With Familial Chylomicronemia Syndrome Treated With Olezarsen: A Post Hoc Analysis of Balance Study Data (ISPOR-EU 2025) - "In the Balance study, olezarsen was associated with fewer AP- and AP- or abdominal pain-related hospitalizations and reduced inpatient days versus placebo in patients with FCS, suggesting that healthcare costs may be lowered with this treatment. Long-term data from clinical practice is expected to provide additional supportive evidence."

Clinical • HEOR • Retrospective data • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

Olezarsen for Managing Severe Hypertriglyceridemia and Pancreatitis Risk. (PubMed, N Engl J Med) - P3 | "Among patients with severe hypertriglyceridemia, treatment with olezarsen led to a significantly greater reduction in the triglyceride level at 6 months and in the incidence of acute pancreatitis than placebo. (Funded by Ionis Pharmaceuticals; CORE-TIMI 72a and CORE2-TIMI 72b ClinicalTrials.gov numbers, NCT05079919 and NCT05552326.)."

Journal • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia • APOC3

Olezarsen in Patients with Severe Hypertriglyceridemia: The CORE-TIMI 72a and CORE2-TIMI 72b Trials (AHA 2025) - "Additionally, a combined total of 333 subjects participated in the hepatic MRI substudy. Primary and secondary results are pending trial completion."

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

Groundbreaking pivotal study results of olezarsen for severe hypertriglyceridemia (sHTG) presented as a late breaker at AHA Scientific Sessions (Ionis Pharmaceuticals Press Release) - "Up to 72% placebo-adjusted mean reduction in fasting triglyceride levels at six months, with reductions sustained through 12 months...86% of olezarsen-treated patients achieved triglyceride levels less than 500 mg/dL, below the risk threshold for acute pancreatitis....Ionis is on track to submit a supplemental new drug application for both the 50 mg and 80 mg doses to the FDA by the end of the year."

FDA filing • Late-breaking abstract • P3 data • Severe Hypertriglyceridemia

Olezarsen: FDA approval and clinical impact in familial chylomicronemia syndrome (FCS). (PubMed, Ann Med Surg (Lond)) - "Furthermore, the drug exemplifies the integration of computational biology and precision medicine, laying the foundation for AI-driven innovations in managing rare lipid disorders. Overall, olezarsen represents a major advancement in FCS treatment, addressing an urgent unmet clinical need and reshaping the therapeutic landscape of ultra-rare metabolic diseases."

FDA event • Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia • 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

TRYNGOLZA (olezarsen), the first and only FDA approved treatment for adults living with familial chylomicronemia syndrome (FCS) as an adjunct to diet (Businesswire) - "Approved in the European Union (EU) as an adjunct to diet in adult patients for the treatment of genetically confirmed FCS; Sobi anticipates launching in the fourth quarter 2025....sNDA submission on track for the end of 2025 with approval anticipated in the fourth quarter of 2026."

EMA approval • FDA approval • FDA filing • Launch Europe • Familial Chylomicronemia Syndrome

Detailed data from the landmark CORE and CORE2 pivotal studies of olezarsen for sHTG to be presented as a late breaker at AHA Scientific Sessions (Businesswire) - "Ionis plans to submit a supplemental new drug application to the U.S. Food and Drug Administration by the end of the year."

FDA filing • P3 data • Severe Hypertriglyceridemia

Ionis reports third quarter 2025 financial results… (Businesswire) - "Revenue increased 17% in the third quarter of 2025 and increased 55% in the nine months ended September 30, 2025, compared to the same periods last year, driven by the continued successful launch of TRYNGOLZA and increased royalty revenues. Contributing to the year-to-date increase, Ionis earned a $280 million upfront payment for the global license of sapablursen to Ono Pharmaceutical Co., Ltd. in the second quarter of 2025."

Commercial • Familial Chylomicronemia Syndrome • Myeloproliferative Neoplasm • Polycythemia Vera

TRYNGOLZA generated $32 million in net product sales in the third quarter 2025 (Businesswire) - "

Sales • Familial Chylomicronemia Syndrome

Tryngolza: Regulatory submission in EU for multifactorial chylomicronemia in 2026 (Swedish Orphan Biovitrum) - Q3 2025 Results

EMA filing • Hypertriglyceridemia • Metabolic Disorders

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

Journal

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

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