solbinsiran (LY3561774) / Eli Lilly, Novo Nordisk - LARVOL DELTA

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

Durability and efficacy of solbinsiran, a GalNAc-conjugated siRNA targeting ANGPTL3, in adults with mixed dyslipidaemia (PROLONG-ANG3): a double-blind, randomised, placebo-controlled, phase 2 trial. (PubMed, Lancet) - P2 | "Solbinsiran 400 mg reduced apoB in patients with mixed dyslipidaemia and was generally well tolerated. The impact of solbinsiran on cardiovascular outcomes remains to be investigated."

Journal • P2 data • Atherosclerosis • Cardiovascular • Dyslipidemia • Mixed Hyperlipidemia • ANGPTL3 • APOB

Effect Of Solbinsiran, A Small Interfering RNA Targeting ANGPTL3, On Biomarkers Of Major Adverse Cardiovascular Events In Adults With Mixed Dyslipidemia: A Randomized Phase 2 Trial - Kausik K. Ray (ACC 2025) - No abstract available

Adverse events • Biomarker • Clinical • Late-breaking abstract • P2 data • Cardiovascular • Dyslipidemia • Metabolic Disorders • Mixed Hyperlipidemia • ANGPTL3

Effect of ANGPTL3 Inhibition With Solbinsiran in Preclinical and Early Human Studies. (PubMed, J Am Coll Cardiol) - P1 | "Solbinsiran inhibits hepatic ANGPTL3 translation and results in significant reductions in all atherogenic lipoproteins in mixed dyslipidemia. The impact of this approach on cardiovascular outcomes remains to be determined. (A Study of LY3561774 in Participants With Dyslipidemia; NCT04644809)."

Journal • Preclinical • Cardiovascular • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Mixed Hyperlipidemia • ANGPTL3 • APOB

Novel RNA-Based Therapies in the Management of Dyslipidemias. (PubMed, Int J Mol Sci) - "This article discusses the latest data from completed and ongoing trials on RNA therapies for dyslipidemia, including inclisiran, pelacarsen, olpasiran, zerlasiran, lepodisiran, volanesorsen, olezarsen, plozasiran, zodasiran, and solbinsiran. Each therapy targets specific molecules while also significantly impacting other lipid parameters. The promising results of these trials indicate potential improvements in lipid therapy and cardiovascular risk reduction, with ongoing studies expected to further refine the role of the novel RNA-based agents in effective lipid management."

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

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

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

PROLONG-ANG3: A Study of LY3561774 in Participants With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=204 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders • APOB

SOLBINSIRAN, A GALNAC-CONJUGATED SIRNA TARGETING ANGPTL3, REDUCES ATHEROGENIC LIPOPROTEINS IN INDIVIDUALS WITH MIXED DYSLIPIDAEMIA IN A DURABLE AND DOSE-DEPENDENT MANNER (ACC 2024) - P1 | "Solbinsiran has potential as a therapeutic option for inhibiting synthesis of ANGPTL3 and reducing TG and atherogenic apoB-containing lipoproteins (NCT04644809)."

Clinical • Dyslipidemia • ANGPTL3 • APOB

Identification and Characterization of Solbinsiran, a GalNAc Conjugated siRNA Targeting Angiopoietin-Like 3 (AHA 2023) - P1 | "These data supported the advancement of solbinsiran to Phase 1 clinical testing in participants with mixed dyslipidemia (ClinicalTrials.gov Identifier: NCT04644809)."

Dyslipidemia • Hepatology • Metabolic Disorders • ANGPTL3 • APOB

PROLONG-ANG3: A Study of LY3561774 in Participants With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=175 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Metabolic Disorders • ANGPTL3 • APOB

PROLONG-ANG3: A Study of LY3561774 in Participants With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=175 | Recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: Sep 2023 ➔ Jan 2024

Trial primary completion date • Dyslipidemia • Metabolic Disorders • APOB

PROLONG-ANG3: A Study of LY3561774 in Participants With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=175 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2023 ➔ Mar 2024

Trial completion date • Dyslipidemia • Metabolic Disorders • APOB

PROLONG-ANG3: A Study of LY3561774 in Participants With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=225 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Mar 2024 ➔ Dec 2023

Trial completion date • Dyslipidemia • Metabolic Disorders • APOB

A Study of LY3561774 in Participants With Dyslipidemia (clinicaltrials.gov) - P1 | N=74 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Metabolic Disorders

PROLONG-ANG3: A Study of LY3561774 in Participants With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=225 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2023 ➔ Mar 2024

Enrollment open • Trial completion date • Dyslipidemia • Metabolic Disorders • APOB

PROLONG-ANG3: A Study of LY3561774 in Participants With Mixed Dyslipidemia (clinicaltrials.gov) - P2 | N=225 | Not yet recruiting | Sponsor: Eli Lilly and Company | Trial primary completion date: May 2023 ➔ Sep 2023

Trial primary completion date • Dyslipidemia • Metabolic Disorders • APOB