zodasiran (ARO-ANG3) / Arrowhead Pharmaceuticals, Visirna Therapeutics - LARVOL DELTA

Zodasiran in mixed hyperlipidaemia: durable lipid lowering, cardiovascular benefit unresolved. (PubMed, Eur J Prev Cardiol) - No abstract available

Journal • Cardiovascular • Dyslipidemia • Mixed Hyperlipidemia

A phase 3 clinical trial to evaluate the efficacy and safety of vsa003 injection in chinese adolescents and adults with homozygous familial hypercholesterolaemia (hofh) (ESC 2026) - No abstract available

Clinical • Late-breaking abstract • P3 data • Cardiovascular • Dyslipidemia

A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE) (clinicaltrials.gov) - P3 | N=70 | Active, not recruiting | Sponsor: Arrowhead Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Announced that the Company completed enrollment in the global Phase 3 YOSEMITE clinical trial of zodasiran… (Arrowhead Press Release) - "The Company anticipates that YOSEMITE will be completed in mid-2027 and, pending successful clinical results, intends to seek regulatory approval in multiple geographies thereafter; YOSEMITE was initially designed to enroll 60 participants with HoFH; however, strong global patient and physician interest led to an increase in target enrollment to 70 patients."

Enrollment closed • Trial completion date • Homozygous Familial Hypercholesterolemia

Longer-Term Efficacy and Safety of Zodasiran in Patients with Mixed Hyperlipidaemia. (PubMed, Eur J Prev Cardiol) - P2 | "Zodasiran produced sustained reductions in triglycerides and atherogenic lipoproteins over 30 months and was well tolerated, supporting its potential as a long-term therapeutic option for mixed hyperlipidaemia."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia • ANGPTL3 • APOB

SPRUCE: Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia (clinicaltrials.gov) - P3 | N=12 | Not yet recruiting | Sponsor: Arrowhead Pharmaceuticals | Trial completion date: May 2029 ➔ Aug 2028 | Initiation date: Mar 2026 ➔ Aug 2026

Trial completion date • Trial initiation date • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Gateway: Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH) (clinicaltrials.gov) - P2 | N=18 | Terminated | Sponsor: Arrowhead Pharmaceuticals | Active, not recruiting ➔ Terminated; Business decision, unrelated to safety concerns.

Trial termination • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Promise of ANGPTL3 as a therapeutic target for controlling cholesterol levels. (PubMed, Expert Opin Ther Targets) - "These observations rapidly catalyzed the development of pharmacologic strategies to inhibit ANGPTL3 using monoclonal antibodies (e.g. evinacumab), antisense oligonucleotides (e.g. vupanorsen), small interfering ribonucleic acid (e.g. zodasiran and solbinsiran), and most recently genome-editing approaches (e.g. VERVE-201 and CTX310). The degree of hypertriglyceridemia in the patient's baseline lipid profile appears to be an important determinant of drug response. Drawing on genetic, mechanistic, and clinical trial data, the promise and limitations of ANGPTL3 inhibition are considered and its potential place in future lipid-lowering strategies is outlined."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • ANGPTL3

A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects With Homozygous Familial Hypercholesterolemia (YOSEMITE) (clinicaltrials.gov) - P3 | N=60 | Recruiting | Sponsor: Arrowhead Pharmaceuticals

Trial initiation date • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

A Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of VSA003 in Chinese HoFH Patients (clinicaltrials.gov) - P3 | N=46 | Active, not recruiting | Sponsor: Visirna Therapeutics HK Limited | Not yet recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2026 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

Current and Emerging Pharmacological Therapies for Hypertriglyceridemia. (PubMed, Int J Mol Sci) - "Emerging therapies such as antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) directed against ApoC-III (volanesorsen, olezarsen, and plozasiran), inhibitors of ANGPTL3 (evinacumab and zodasiran), and fibroblast growth factor 21 (FGF-21) analogs (pegozafermin) have demonstrated substantial triglyceride-lowering efficacy. The therapeutic landscape for hypertriglyceridemia is rapidly evolving. Integrating these novel agents into clinical practice will require individualized treatment plans, sustained lifestyle modification, and careful safety monitoring."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • ANGPTL3 • FGF21 • LPL

Novel Approaches to Lipid Management: Beyond Statins and PCSK9 Inhibitors. (PubMed, J Clin Med Res) - "The statins remain the foundation of lipid management because they lower low-density lipoprotein cholesterol (LDL-C) and prevent cardiovascular events, and guidelines recommend stepwise intensification, often with ezetimibe first, when targets are not met or when intolerance limits dosing...FOURIER and ODYSSEY OUTCOMES demonstrated event reduction with evolocumab or alirocumab on background statin therapy. For patients who cannot tolerate adequate statin doses, bempedoic acid provides liver-selective inhibition of adenosine triphosphate (ATP)-citrate lyase, and CLEAR Outcomes showed fewer major cardiovascular events in statin-intolerant populations. Inclisiran extends PCSK9 pathway suppression through hepatic small interfering RNA (siRNA) and enables durable LDL-C reduction with twice-yearly maintenance dosing, offering an adherence-oriented alternative while outcomes data mature. Angiopoietin-like protein 3 (ANGPTL3)-directed therapies (evinacumab and investigational..."

Journal • Review • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • ANGPTL3 • PCSK9

Effect of angiopoietin-like protein 3 inhibitors on lipid profile and other biomarkers: a meta-analysis of randomized controlled trials. (PubMed, Eur J Prev Cardiol) - "ANGPTL3 inhibition offers broad lipid-lowering benefits, with particularly marked reductions in TG-rich lipoproteins."

Biomarker • Journal • Retrospective data • Cardiovascular • Dyslipidemia • ANGPTL3 • APOA1 • APOB • APOE • CRP

Zodasiran for cholesterol and triglyceride lowering in patients with hyperlipidemia: final report of phase 1 basket trial. (PubMed, Nat Med) - P1 | "These results indicate a favorable safety profile for zodasiran, with promise for correcting isolated hypercholesterolemia and moderate-to-severe hypertriglyceridemia, and support further studies of zodasiran in treating a wide spectrum of dyslipidemias. ClinicalTrials.gov registration: NCT03747224 ."

Journal • P1 data • Pan tumor • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders • Severe Hypertriglyceridemia • ANGPTL3

SPRUCE: Study of Zodasiran in Adolescent Participants With Homozygous Familial Hypercholesterolemia (clinicaltrials.gov) - P3 | N=12 | Not yet recruiting | Sponsor: Arrowhead Pharmaceuticals

New P3 trial • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

AROANG3-3001: A Phase 3 Study of Zodasiran in Adolescent and Adult Subjects WithnHomozygous Familial Hypercholesterolemia (YOSEMITE) (clinicaltrialsregister.eu) - P2/3 | N=18 | Not yet recruiting | Sponsor: Arrowhead Pharmaceuticals Inc.

New P2/3 trial • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders

Angiopoietin-like Protein 3 (ANGPTL3) Targeting in the Management of Dyslipidemias. (PubMed, Int J Mol Sci) - "We also discuss Evinacumab, a monoclonal antibody, its structure, mechanism of action, safety, tolerability, pharmacokinetics, and pharmacodynamics, as well as its clinical trial-derived results. The antisense oligonucleotides modify ANGPTL3 mRNA to inhibit protein production, and small interfering RNAs induce mRNA degradation; results from clinical trials were reviewed in detail. Finally, we discuss promising gene editing approaches including clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems."

Journal • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders • ANGPTL3

Zodasiran, an RNAi therapeutic targeting ANGPTL3, for treating patients with homozygous familial hypercholesterolaemia (GATEWAY): an open-label, randomised, phase 2 trial. (PubMed, Lancet Diabetes Endocrinol) - P2 | "Quarterly dosed zodasiran shows evidence of reductions in LDL cholesterol with a favourable safety profile, in patients with HoFH receiving background lipid-lowering therapy. Further investigation in phase 3 trials is warranted."

Journal • P2 data • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Homozygous Familial Hypercholesterolemia • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • ANGPTL3

Dosed the first subject in the YOSEMITE Phase 3 clinical trial of zodasiran, the company’s investigational RNAi therapeutic being developed as a potential treatment for homozygous familial hypercholesterolemia (HoFH) (Businesswire)

Trial status • Homozygous Familial Hypercholesterolemia

CT.MDP.24: Closing the LDL Gap: Innovations, Access, and Adherence in Lipid-Lowering Therapy (AHA 2025) - "Discover the real-world impact of evolocumab, cost and utilization trends in under-treated populations, and access inequities driven by socioeconomic deprivation. With new evidence on emerging agents like bempedoic acid, obicetrapib, and zodasiran, this session brings together cutting-edge science and pragmatic solutions to confront one of cardiology's most persistent challenges: getting LDL down and keeping it there. This is not a CE accredited session."

Adherence • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders

Future of angiopoietin-like protein 3 inhibitors as a therapeutic agent. (PubMed, Curr Opin Lipidol) - "ANGPTL3 inhibition offers an LDL receptor-independent means to lower atherogenic particles spanning from TRLs to LDL, complementing traditional lipid-lowering therapies. Evinacumab is practice-changing in HoFH, and RNA agents may soon broaden applicability to patients with mixed dyslipidemia and residual cardiovascular risk, pending cardiovascular outcomes trials."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • Mixed Hyperlipidemia • ANGPTL3

RNA INTERFERENCE OF ANGPTL3 VIA ZODASIRAN: A NEXT-GENERATION APPROACH FOR TREATING ATHEROGENIC DYSLIPIDEMIA (AHA 2025) - "RNAi-mediated ANGPTL3 inhibition via zodasiran is a promising strategy for managing atherogenic dyslipidemia and cardiovascular risk. Its hepatocyte-specific action, prolonged dosing, and safety profile offer benefits over current treatments, especially for familial hypercholesterolemia and statin-intolerant patients. Long-term outcome trials are needed to confirm clinical benefit."

Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Metabolic Disorders • Mixed Hyperlipidemia • ANGPTL3 • APOB

YOSEMITE Rationale and Design: Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Zodasiran Efficacy and Safety in Adolescents and Adults with Homozygous Familial Hypercholesterolemia (AHA 2025) - "Secondary endpoints include percent change from baseline in fasting ApoB, non-HDL-C, TGs, ANGPTL3, total cholesterol, Lp(a) and HDL-C; change from baseline and AUC in fasting LDL-C to 1-year. Safety and tolerability will be assessed.ConclusionsYOSEMITE is designed to determine whether quarterly-dosed zodasiran safely reduces LDL-C levels in patients with HoFH."

Clinical • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • ANGPTL3 • APOB • LDLR

Gateway: Study of ARO-ANG3 in Participants With Homozygous Familial Hypercholesterolemia (HOFH) (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: Arrowhead Pharmaceuticals | Trial completion date: May 2025 ➔ Nov 2025

Trial completion date • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Homozygous Familial Hypercholesterolemia • Metabolic Disorders • APOB

A VSA003 Phase 1 Study in Chinese Adult Healthy Volunteers (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Visirna Therapeutics HK Limited | Not yet recruiting ➔ Completed

Trial completion • Dyslipidemia • Familial Hypercholesterolemia • Genetic Disorders • Hypertriglyceridemia • Metabolic Disorders