Tryngolza (olezarsen) / Ionis, Theratechnologies - LARVOL DELTA

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

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

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

Clinical • Cardiovascular • Dyslipidemia

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

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

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

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

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

Efficacy and Safety of Olezarsen in Dyslipidemia: A Systematic Review and Dose-response Meta-analysis of Randomized Controlled Trials. (PubMed, J Saudi Heart Assoc) - "In conclusion, olezarsen is an effective Apo-C3 inhibitor that improves lipid profiles with a favorable safety profile. This modeling-based insight refines previous findings by delineating a clearer therapeutic window."

Journal • Retrospective data • Review • Dyslipidemia • Hematological Disorders • Metabolic Disorders

The ASO drug olezarsen targets familial chylomicronemia syndrome. (PubMed, Trends Pharmacol Sci) - No abstract available

Journal • Familial Chylomicronemia Syndrome

Clinical Pharmacology of Olezarsen, a Novel ApoC-III Targeted Antisense Inhibitor, for Reducing Triglycerides in Patients with Familial Chylomicronemia Syndrome (NLA 2025) - P1, P2, P3 | "Conclusions The overall clinical pharmacology properties of olezarsen are favorable and support the recommended dosing regimen of 80 mg olezarsen subcutaneous injection once monthly as safe and effective treatment in adults with FCS. No dose adjustment is required for intrinsic/extrinsic factors."

Clinical • Familial Chylomicronemia Syndrome

Comparison of diagnostic genetic testing and clinical scoring results for familial chylomicronemia syndrome (FCS) in the 66-patient Balance study (NLA 2025) - "Objective/Purpose To evaluate the sensitivity of the NAFCS scoring system in the 66 genetically identified FCS patients enrolled in Balance, a phase 3 study on the efficacy and safety of olezarsen...In Balance, the NAFCS score showed a sensitivity of 74% for the highly selective score of ≥ 60 and 95% for ≥ 45. These results suggest that the NAFCS scoring system might simplify diagnosis of FCS, supporting earlier access to treatment."

Clinical • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • APOB

A Single-Dose, Randomized, Open-Label, Two-Period Crossover Bioequivalence Study in Healthy Adults Comparing Two Subcutaneous Formulations of Olezarsen: (Vial and Autoinjector) at Two Dose Levels (NLA 2025) - P1 | "Olezarsen was well-tolerated with no clinically meaningful differences in safety profiles between formulations. Conclusions This study demonstrated the therapeutic equivalence of the olezarsen autoinjector and vial presentations at both 50 mg and 80 mg doses, supporting the interchangeable use of these formulations at the same dose."

Clinical • Familial Chylomicronemia Syndrome

† Olezarsen for hypertriglyceridemia in patients at high cardiovascular risk - A systematic review and meta-analysis (NLA 2025) - "Despite higher rates of serious adverse events, its overall safety profile remains acceptable. Further long-term studies are necessary to confirm these findings and optimize dosing."

Retrospective data • Review • Cardiovascular • Dyslipidemia • Gastrointestinal Disorder • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • APOA1 • APOB • APOC3

Prevalence, baseline characteristics, and reclassification of indeterminate genetic results in patients eligible for the Balance trial with olezarsen (NLA 2025) - P3 | "In patients with indeterminate genetic results, pending refinement of genetic testing, consideration should be given for using clinical risk scores to diagnose FCS. A global curated public database of FCS-related DNA variants in racially diverse populations may allow more accurate classification of pathogenic FCS variants."

Clinical • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • APOB

Ionis announces positive topline results from Essence study of olezarsen in people with moderately elevated triglycerides (Ionis Pharmaceuticals Press Release) - P3 | N=1,478 | Essence-TIMI 73b (NCT05610280) | Sponsor: Ionis Pharmaceuticals, Inc. | "Ionis Pharmaceuticals...announced positive topline results from the Essence study of olezarsen in people with moderate hypertriglyceridemia (fasting triglycerides ≥150 mg/dL to <500 mg/dL) with or at risk for atherosclerotic cardiovascular disease (ASCVD). Nearly all the participants were on current standard of care lipid-lowering medicines. The trial met its primary endpoint with a statistically significant placebo-adjusted 61% and 58% reduction in triglyceride (TG) levels at 6 months with the 80 mg and 50 mg monthly doses, respectively (p <0.0001). Olezarsen also met all key secondary endpoints in the study. The vast majority of participants reached <150mg/dL, reflecting a reduction to normal TG levels. Olezarsen demonstrated a favorable safety and tolerability profile in the study. Ionis plans to submit an abstract for presentation at an upcoming scientific conference."

P3 data: top line • Hypertriglyceridemia

Ionis Pharmaceuticals targets $750M revenue for 2025 with multiple launches underway (MSN News) - "The company is preparing for several upcoming launches, including donidalorsen for hereditary angioedema (HAE) in Q3 2025 and olezarsen for severe hypertriglyceridemia (sHTG) next year, positioning Ionis for substantial growth....The company plans to submit a supplemental New Drug Application (sNDA) for olezarsen by year-end, following Phase III data from CORE and CORE2 studies expected in Q3 2025."

FDA filing • Launch • P3 data • Hereditary Angioedema • Severe Hypertriglyceridemia

CORE-OLE: A Study of Olezarsen (ISIS 678354) Administered Subcutaneously to Participants With Severe Hypertriglyceridemia (SHTG) (clinicaltrials.gov) - P3 | N=800 | Recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial completion date: Sep 2026 ➔ Mar 2027 | Trial primary completion date: May 2026 ➔ Mar 2027

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

Ionis reports first quarter 2025 financial results (Businesswire) - "TRYNGOLZA (olezarsen), the first-ever treatment for adults living with familial chylomicronemia syndrome (FCS) as an adjunct to diet, generated net product sales of over $6 million in its first full quarter following approval in the U.S. on December 19, 2024; Commercialization rights in countries outside of the U.S., Canada and China licensed to Sobi; EU approval decision anticipated in H2:2025." "

EMA approval • Sales • Familial Chylomicronemia Syndrome

Novel Therapeutics for Familial Chylomicronemia Syndrome. (PubMed, Curr Atheroscler Rep) - "Volanesorsen, an ASO targeting APOC3, has shown effectiveness in managing FCS, multifactorial chylomicronemia, and familial partial lipodystrophy, but its use is limited by thrombocytopenia. Emerging therapies, Olezarsen (ASO anti-APOC3) and Plozasiran (siRNA anti-APOC3), both conjugated with GalNAc, show promise in reducing acute pancreatitis risk without platelet concerns. ANGPTL3 inhibition requires residual lipoprotein lipase (LPL) activity, with only siRNA-based therapies-zodasiran and solbinsiran-under investigation. Suppressing APOC3 expression and targeting ANGPTL3 via siRNA offer significant potential, but long-term studies are needed to confirm their efficacy and safety. Future research may explore gene-editing strategies using lipid nanoparticle-based CRISPR-Cas9 delivery for more durable treatment outcomes."

Journal • Review • Familial Chylomicronemia Syndrome • Hematological Disorders • Lipodystrophy • Metabolic Disorders • Pancreatitis • Rare Diseases • Thrombocytopenia • ANGPTL3 • APOC3 • LPL

Olezarsen for the Treatment of Familial Chylomicronemia Syndrome. (PubMed, Ann Pharmacother) - "Olezarsen represents a new treatment for FCS, offering a targeted approach to significantly reduce triglyceride levels. Its integration into clinical practice has the potential to transform the management of FCS; however, more studies are needed to firmly establish its role."

Journal • Review • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Infectious Disease • Novel Coronavirus Disease • Pain • Severe Hypertriglyceridemia • Targeted Protein Degradation • APOC3

A Study of Olezarsen (ISIS 678354) in Participants With Hypertriglyceridemia and Atherosclerotic Cardiovascular Disease, or With Severe Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=1478 | Active, not recruiting | Sponsor: Ionis Pharmaceuticals, Inc. | Trial primary completion date: Mar 2025 ➔ Aug 2024

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