---
title: "Solbinsiran: Lilly's ANGPTL3-Silencing RNAi Injection That Lowers LDL and Triglycerides Together - Inside the Phase 2 PROLONG-ANG3 Trial (August 16, 2026) | PepTracker Pro Blog"
url: https://peptrackerpro.com/blog/solbinsiran-lilly-ly3561774-angptl3-galnac-sirna-rnai-apob-triglycerides-ldl-remnant-cholesterol-mixed-dyslipidemia-prolong-ang3-phase-3-cardiovascular-outcomes-august-16-2026
description: "Statins lower LDL, but many patients still carry risk from triglyceride-rich remnants. Solbinsiran, Lilly's investigational GalNAc-siRNA, silences the liver protein ANGPTL3 to cut LDL and triglycerides at the same time - with an injection given only a few times a year. Here is what the Phase 2 PROLONG-ANG3 trial showed, how solbinsiran compares with the other ANGPTL3 siRNA zodasiran, and why a Phase 3 cardiovascular outcomes trial is being built on the results."
lang: en
---

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Research & Compounds

Research & Compounds

# Solbinsiran: Lilly's ANGPTL3-Silencing RNAi Injection That Lowers LDL and Triglycerides Together - Inside the Phase 2 PROLONG-ANG3 Trial (August 16, 2026)

PepTracker Pro Research Team August 16, 2026 8 min read

## Table of Contents

- Lowering two lipids with one switch
- What ANGPTL3 does, and why silencing it helps
- How solbinsiran is built: GalNAc-siRNA
- PROLONG-ANG3: the Phase 2 test
- What the numbers showed
- Safety and tolerability
- Solbinsiran vs zodasiran: two ANGPTL3 siRNAs
- Where it sits in the RNAi wave
- What to keep in mind

## Lowering two lipids with one switch

Most people who have heart attacks and strokes carry two lipid problems at once: too much LDL cholesterol and too many triglyceride-rich particles. Statins handle LDL well, but a lot of treated patients still have leftover risk from triglyceride remnants. Solbinsiran (development code LY3561774), an investigational RNA interference therapeutic from Eli Lilly, is designed to hit both at the same time. It silences a single liver protein, ANGPTL3, and by doing so lowers triglycerides, remnant cholesterol and LDL cholesterol together - with an injection given only a few times a year.

## What ANGPTL3 does, and why silencing it helps

ANGPTL3 (angiopoietin-like protein 3) is made by the liver and acts as a brake on two fat-clearing enzymes, lipoprotein lipase and endothelial lipase. When those enzymes are held back, triglyceride-rich particles and their cholesterol-laden remnants linger in the blood. Turn ANGPTL3 down and the brakes come off: the body clears triglycerides and remnant cholesterol faster, and LDL cholesterol falls too. The target has strong human genetic backing - people born with loss-of-function ANGPTL3 variants naturally run low triglycerides and LDL and appear protected against coronary artery disease, a natural experiment solbinsiran is built to imitate.

## How solbinsiran is built: GalNAc-siRNA

Solbinsiran is a small interfering RNA (siRNA) conjugated to GalNAc (N-acetylgalactosamine), a sugar tag that binds a receptor found almost exclusively on liver cells. That tag delivers the siRNA straight to hepatocytes, where it latches onto the messenger RNA for ANGPTL3 and marks it for destruction before the protein can be made. Because the delivery is targeted and the silencing durable, solbinsiran can be given as a small subcutaneous injection once every few months. The chemistry matters for another reason: an earlier antisense drug against ANGPTL3, vupanorsen, was discontinued over dose-dependent liver problems, and the GalNAc-siRNA approach is meant to achieve deep silencing at low doses without that toxicity.

## PROLONG-ANG3: the Phase 2 test

The PROLONG-ANG3 trial, published in The Lancet in 2025, was a double-blind, randomized, placebo-controlled Phase 2 study of 205 adults with mixed dyslipidemia already taking moderate- or high-intensity statins, run across 41 sites in seven countries. Participants were assigned 1:2:2:2 to solbinsiran 100 mg, 400 mg or 800 mg, or placebo, given as a subcutaneous injection on day 0 and again at day 90, then followed for at least 270 days. The population was about 54% female with a median age of 57, and baseline apolipoprotein B averaged 111 mg/dL.

## What the numbers showed

The primary endpoint was the placebo-adjusted change in apolipoprotein B (apoB) - a count of the atherogenic particles - at day 180. The 400 mg dose lowered apoB by 14.3% (95% CI -23.6 to -3.9; P=0.0085), the only dose to reach statistical significance; the 100 mg (-2.8%) and 800 mg (-8.3%) doses did not, an unusual non-monotonic pattern the investigators reported honestly. Across doses, apoB reductions of roughly 11% were sustained out to day 270 - months after the last injection. The 400 mg dose also cut liver fat by about 28%, and earlier repeat-dose data had shown ANGPTL3 falling around 89%, triglycerides up to about 70% and LDL up to about 42%.

## Safety and tolerability

Solbinsiran was well tolerated. Treatment-emergent adverse events were no more common than with placebo - about 52% in the 400 mg group versus 65% on placebo - and hepatic MRI before and after six months of treatment showed no dose-dependent liver harm. In fact liver fat went down. That clean liver-safety readout is significant given that hepatotoxicity ended the earlier ANGPTL3 antisense program, and it is a big part of why Lilly's investigators framed the results as a platform to build on rather than a signal to worry about.

## Solbinsiran vs zodasiran: two ANGPTL3 siRNAs

Solbinsiran is not the only siRNA aimed at ANGPTL3. Arrowhead's zodasiran (ARO-ANG3) hits the same target with the same GalNAc-siRNA approach, but the two programs are pointed at different populations. Zodasiran's late-stage development has focused on homozygous familial hypercholesterolemia (HoFH), a rare inherited disease in which the LDL receptor barely works and ANGPTL3's LDL-receptor-independent action is especially valuable; its Phase 3 YOSEMITE trial completed enrollment in July 2026. Solbinsiran, by contrast, is being developed for the far larger group of statin-treated patients with mixed dyslipidemia and high cardiovascular risk. An approved antibody, evinacumab, also blocks ANGPTL3 but must be infused intravenously; both siRNAs instead shut off production of the protein upstream with an occasional injection.

## Where it sits in the RNAi wave

Solbinsiran is part of a broader wave of GalNAc-siRNA and antisense drugs remaking lipid and cardiovascular medicine. Others in the family aim at Lp(a) (olpasiran, lepodisiran, zerlasiran, pelacarsen), apoC-III (plozasiran, olezarsen) and even blood pressure via angiotensinogen (zilebesiran). ANGPTL3 gives solbinsiran and zodasiran a broad footprint - triglycerides, remnant cholesterol and LDL at once - and solbinsiran's dual LDL-plus-triglyceride effect, durable dosing and clean liver profile make it a leading candidate to test whether ANGPTL3 lowering actually prevents heart attacks and strokes.

## What to keep in mind

Solbinsiran is investigational and not approved for any use. Its data come from Phase 1 and Phase 2 trials, and it has not yet been shown to reduce heart attacks or strokes - that cardiovascular outcome evidence is a separate, longer question that a planned Phase 3 program is being built to answer. Because RNA interference produces deep, months-long silencing, the effect of a dose cannot be quickly reversed, and metabolic measures warrant ongoing monitoring. It is an injectable biologic used only under medical supervision in clinical trials - not a supplement or research chemical - and any product marketed as 'solbinsiran' or 'LY3561774' outside a trial is unverified and unsafe. This article is educational and not medical advice.

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## Citations

1. [1] Ray KK, et al. - 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, The Lancet (2025) Source (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00507-0/fulltext)
2. [2] Ray KK, Linnebjerg H, Michael LF, et al. - Effect of ANGPTL3 Inhibition With Solbinsiran in Preclinical and Early Human Studies, JACC (2025) Source (https://www.jacc.org/doi/10.1016/j.jacc.2025.03.005)
3. [3] PROLONG-ANG3 (solbinsiran, phase 2 trial) - PubMed record Source (https://pubmed.ncbi.nlm.nih.gov/40179932/)
4. [4] Solbinsiran Significantly Reduces apoB in Mixed Dyslipidemia in Phase 2 Trial - HCPLive (ACC.25 coverage) Source (https://www.hcplive.com/view/solbinsiran-significantly-reduces-apob-in-mixed-dyslipidemia-in-phase-2-trial)
5. [5] Eli Lilly's siRNA Lowers Key Cardiovascular Disease Biomarkers in Phase II Mixed Dyslipidemia Trial - Precision Medicine Online Source (https://www.precisionmedicineonline.com/cardiovascular-disease/eli-lillys-sirna-lowers-key-cardiovascular-disease-biomarkers-phase-ii-mixed)

**Disclaimer:** This article is for educational purposes only and does not constitute medical advice. Always consult a licensed healthcare provider. Read full research disclaimer → (https://peptrackerpro.com/research-disclaimer)

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