--- title: "Zodasiran | PepTracker Pro" url: https://peptrackerpro.com/peptides/zodasiran description: "An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Arrowhead Pharmaceuticals that lowers atherogenic lipids by silencing ANGPTL3 (angiopoietin-like protein 3), a liver-made regulator of fat metabolism. By switching off ANGPTL3 production, zodasiran deeply reduces triglycerides, remnant cholesterol and LDL cholesterol through a pathway that does not depend on the LDL receptor - making it especially relevant for people, such as those with homozygous familial hypercholesterolemia (HoFH), whose LDL receptors barely work. In the Phase 2b ARCHES-2 trial (NEJM 2024) it produced durable, dose-dependent reductions in triglycerides, remnant cholesterol and ANGPTL3, and in the Phase 2 GATEWAY study it lowered LDL cholesterol by about 40% in HoFH. It is now in the Phase 3 YOSEMITE trial in HoFH, which completed enrollment in July 2026." lang: en --- Skip to main content **Educational information only.** This site does not provide medical advice. Read full disclaimer (https://peptrackerpro.com/disclaimer) **Research-only content.** This page is for educational purposes and does not constitute medical advice. Read full disclaimer → (https://peptrackerpro.com/research-disclaimer) # Zodasiran Medium Evidence An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Arrowhead Pharmaceuticals that lowers atherogenic lipids by silencing ANGPTL3 (angiopoietin-like protein 3), a liver-made regulator of fat metabolism. By switching off ANGPTL3 production, zodasiran deeply reduces triglycerides, remnant cholesterol and LDL cholesterol through a pathway that does not depend on the LDL receptor - making it especially relevant for people, such as those with homozygous familial hypercholesterolemia (HoFH), whose LDL receptors barely work. In the Phase 2b ARCHES-2 trial (NEJM 2024) it produced durable, dose-dependent reductions in triglycerides, remnant cholesterol and ANGPTL3, and in the Phase 2 GATEWAY study it lowered LDL cholesterol by about 40% in HoFH. It is now in the Phase 3 YOSEMITE trial in HoFH, which completed enrollment in July 2026. Aliases ARO-ANG3 +3 more Evidence Medium Evidence Last Updated 2026-08-15 Reading Time 5 min ## What It Is Zodasiran (development code ARO-ANG3) is a GalNAc-conjugated small interfering RNA (siRNA) developed by Arrowhead Pharmaceuticals that targets the messenger RNA for ANGPTL3 (angiopoietin-like protein 3) in the liver. ANGPTL3 is a hepatocyte-made protein that acts as a brake on two fat-clearing enzymes - lipoprotein lipase and endothelial lipase - so when it is switched off, the body clears triglyceride-rich lipoproteins and remnant cholesterol more efficiently and also lowers LDL cholesterol. Crucially, ANGPTL3 inhibition reduces LDL cholesterol through a mechanism that does not rely on the LDL receptor (LDLR), which is why it is being pursued for homozygous familial hypercholesterolemia (HoFH) - a rare inherited disease in which both copies of the LDL-receptor pathway are severely impaired and standard LDL-lowering drugs work poorly. Because the siRNA is conjugated to GalNAc (N-acetylgalactosamine), a sugar tag that binds a receptor found almost exclusively on liver cells, the drug concentrates in the liver where ANGPTL3 is made, allowing a small subcutaneous injection given only once every few months. Human genetics support the target: people who naturally carry loss-of-function ANGPTL3 variants have low triglycerides and LDL cholesterol and appear protected from coronary artery disease. Zodasiran is investigational and not approved for any use; it is a laboratory-made oligonucleotide medicine given only in clinical trials, not a dietary supplement or research chemical. Also known as: ARO-ANG3, ANGPTL3 siRNA, anti-ANGPTL3 siRNA, angiopoietin-like 3 siRNA ## Regulatory Status Investigational (Phase 3; not approved) Zodasiran has not been approved by the FDA or any regulator; it remains investigational. Arrowhead Pharmaceuticals studied it in mixed hyperlipidemia (Phase 2b ARCHES-2) and in homozygous familial hypercholesterolemia (HoFH; Phase 2 GATEWAY), and has advanced it into the pivotal global Phase 3 YOSEMITE study in HoFH - a randomized, double-blind, placebo-controlled trial of 70 patients aged 12 and older assigned 2:1 to zodasiran 200 mg or placebo given subcutaneously once every three months for four doses. YOSEMITE completed patient enrollment on July 27, 2026 (expanded from a planned 60 to 70 patients on strong global interest) and is anticipated to complete in mid-2027, after which Arrowhead intends to seek regulatory approval in multiple geographies pending successful results. Zodasiran is developed by Arrowhead Pharmaceuticals. ## Why Researchers Study It High triglycerides, remnant cholesterol and LDL cholesterol all drive heart attacks and strokes, and some patients cannot get these numbers down with existing drugs - especially people with homozygous familial hypercholesterolemia (HoFH), whose broken LDL receptors make statins and PCSK9 inhibitors far less effective. Zodasiran is interesting because it lowers these lipids by a completely different route: it silences ANGPTL3, a liver protein that normally slows the clearance of fat from the blood, and it does so upstream of and independent of the LDL receptor. That LDLR-independent action is exactly why it may help HoFH patients who have few other options. Human genetics give the target unusual credibility - people born with naturally low ANGPTL3 have low triglycerides and LDL cholesterol and appear protected from coronary disease - so mimicking that genetic state with an occasional injection is an appealing strategy. Scientifically, zodasiran extends the GalNAc-siRNA platform (already used against Lp(a), apoC-III and angiotensinogen with drugs like olpasiran, plozasiran, olezarsen and zilebesiran) to a new lipid target, and its infrequent dosing - as rarely as once every three months - could improve on daily pills. Researchers are studying whether these deep lipid reductions translate into fewer cardiovascular events and whether the approach is safe over the long term, including its effects on liver fat and glucose metabolism. ## Proposed Mechanisms - GalNAc-conjugated small interfering RNA (siRNA) that binds and triggers degradation of the messenger RNA encoding ANGPTL3 (angiopoietin-like protein 3) in hepatocytes, reducing production of the protein - ANGPTL3 normally inhibits lipoprotein lipase and endothelial lipase; lowering it releases those enzymes to clear triglyceride-rich lipoproteins and remnant cholesterol from the circulation more efficiently - Reduces LDL cholesterol through a mechanism that is independent of the LDL receptor (LDLR), which is why it can lower LDL even when LDL-receptor function is severely impaired, as in homozygous familial hypercholesterolemia - GalNAc (N-acetylgalactosamine) conjugation targets the asialoglycoprotein receptor on liver cells, concentrating the siRNA in the liver and enabling low-dose subcutaneous injection at intervals of several months - Recapitulates the low-lipid, apparently cardioprotective state seen in people who naturally carry loss-of-function ANGPTL3 gene variants ## Evidence Snapshot Medium Evidence Low Medium High | Study Type | Model | Outcome | Link | | --- | --- | --- | --- | | Phase 2b (ARCHES-2, NEJM 2024) | 204 adults with mixed hyperlipidemia (triglycerides 150-499 mg/dL and elevated LDL or non-HDL cholesterol) on maximally tolerated statins; subcutaneous zodasiran 50, 100 or 200 mg vs placebo on day 1 and week 12 | Placebo-adjusted Week 24 reductions of about 54-74% in ANGPTL3, 51-63% in triglycerides and 73-82% in remnant cholesterol, with significant falls in non-HDL cholesterol (up to ~36%), LDL cholesterol (up to ~20%) and apolipoprotein B (up to ~22%); reductions durable to Week 36; liver fat by MRI-PDFF fell about 28% at 200 mg in a steatotic subgroup; modest changes in HbA1c | Source | | Phase 2 (GATEWAY, Lancet Diabetes & Endocrinology 2025) | Open-label, randomized study in patients with homozygous familial hypercholesterolemia (HoFH); subcutaneous zodasiran 200 or 300 mg on day 1 and month 3 | LDL cholesterol lowered by approximately 40% through an LDL-receptor-independent mechanism, with no drug discontinuations, drug-related serious adverse events or deaths reported | Source | | Phase 3 (YOSEMITE, enrollment completed July 2026) | Global, randomized, double-blind, placebo-controlled trial in HoFH; 70 patients aged 12 and older assigned 2:1 to zodasiran 200 mg or placebo subcutaneously every 3 months for 4 doses | Pivotal efficacy and safety trial for HoFH; enrollment completed July 27, 2026 (expanded from 60 to 70 patients), anticipated to complete in mid-2027; results not yet available | Source | ## Commonly Discussed Benefits Cardiovascular: https://peptrackerpro.com/benefits/cardiovascular Cholesterol Management: https://peptrackerpro.com/benefits/cholesterol-management Disease Modification: https://peptrackerpro.com/benefits/disease-modification Researching Zodasiran? Track it, set reminders, and keep notes in the free app. Track in App (https://app.peptrackerpro.com/?add=zodasiran) ## Safety & Cautions - Zodasiran is investigational and not approved for any use; efficacy and safety data come from Phase 2/2b trials, and cardiovascular outcome benefit has not been established - Because it produces deep, long-lasting silencing of ANGPTL3, any effects take months to wear off after a dose and cannot be quickly reversed - ANGPTL3 lowering can affect glucose and fat metabolism; trials have monitored measures such as HbA1c and liver fat, and long-term metabolic effects are still being characterized - Injection-site reactions and common infections (such as upper respiratory infections) were among the adverse events reported with the GalNAc-siRNA class in these trials - It is an injectable investigational oligonucleotide biologic used only under medical supervision in clinical trials; it is not a supplement or research chemical, and any 'zodasiran' or 'ARO-ANG3' offered by a vendor is unverified and unsafe - As with any lipid-lowering agent in development, use in pregnancy has not been established and appropriate precautions apply in clinical trials ## Comparisons See how Zodasiran compares to related peptides: Zodasiran vs Eplontersen: https://peptrackerpro.com/compare/zodasiran-vs-eplontersen Zodasiran vs Inclisiran: https://peptrackerpro.com/compare/zodasiran-vs-inclisiran Zodasiran vs Lepodisiran: https://peptrackerpro.com/compare/zodasiran-vs-lepodisiran Zodasiran vs Muvalaplin: https://peptrackerpro.com/compare/zodasiran-vs-muvalaplin Zodasiran vs Obicetrapib: https://peptrackerpro.com/compare/zodasiran-vs-obicetrapib Zodasiran vs Olezarsen: https://peptrackerpro.com/compare/zodasiran-vs-olezarsen Zodasiran vs Olpasiran: https://peptrackerpro.com/compare/zodasiran-vs-olpasiran Zodasiran vs Pelacarsen: https://peptrackerpro.com/compare/zodasiran-vs-pelacarsen Zodasiran vs Plozasiran: https://peptrackerpro.com/compare/zodasiran-vs-plozasiran Zodasiran vs Solbinsiran: https://peptrackerpro.com/compare/zodasiran-vs-solbinsiran Zodasiran vs Vutrisiran: https://peptrackerpro.com/compare/zodasiran-vs-vutrisiran Zodasiran vs Zerlasiran: https://peptrackerpro.com/compare/zodasiran-vs-zerlasiran Zodasiran vs Zilebesiran: https://peptrackerpro.com/compare/zodasiran-vs-zilebesiran Zodasiran vs ARO-INHBE: https://peptrackerpro.com/compare/zodasiran-vs-aro-inhbe ## Calculator Tools Use our research tools to explore dosing and reconstitution data: Reconstitution Calculator: https://peptrackerpro.com/calculators ## Citations 1. [1] Rosenson RS, et al. - Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia (ARCHES-2, Phase 2b), New England Journal of Medicine (2024) PubMed (https://www.nejm.org/doi/full/10.1056/NEJMoa2404147) 2. [2] Arrowhead Pharmaceuticals - Presents New Phase 2 (ARCHES-2) Data of Zodasiran in Patients with Mixed Hyperlipidemia (EAS 2024) PubMed (https://arrowheadpharma.com/en-us/newsroom/arrowhead-pharmaceuticals-presents-new-phase-2) 3. [3] Zodasiran, an RNAi therapeutic targeting ANGPTL3, for treating patients with homozygous familial hypercholesterolaemia (GATEWAY), Lancet Diabetes & Endocrinology (2025) PubMed (https://www.thelancet.com/journals/landia/article/PIIS2213-8587(25)00290-6/abstract) 4. [4] Arrowhead Pharmaceuticals - Completes Enrollment in Global Phase 3 YOSEMITE Study of Zodasiran for HoFH (July 27, 2026) PubMed (https://ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-completes-enrollment-global-phase-3) 5. [5] Arrowhead concludes enrolment for Phase III zodasiran trial in HoFH - Clinical Trials Arena PubMed (https://www.clinicaltrialsarena.com/news/arrowhead-concludes-enrolment-zodasiran-trial/) ### Keep researching in the app - Log Zodasiran to your private tracker - Set a dosing reminder - Compare it side-by-side with your stack Open PepTracker Pro Free: https://app.peptrackerpro.com/?add=zodasiran Browse more peptides: https://peptrackerpro.com/peptides ## Related Peptides ### Eplontersen High Evidence An approved, once-monthly, self-administered subcutaneous GalNAc-conjugated antisense oligonucleotide (ASO) from Ionis and AstraZeneca that treats transthyretin-mediated (ATTR) amyloidosis by lowering the liver's production of transthyretin (TTR). Transthyretin is a liver-made transport protein that can misfold and deposit as amyloid in nerves and the heart; eplontersen is a short synthetic strand of chemically modified DNA/RNA that binds TTR messenger RNA and directs its enzymatic (RNase H1) degradation before the protein is made, cutting circulating TTR by roughly 80%. A triantennary N-acetylgalactosamine (GalNAc) tag delivers it to liver cells, allowing a low-dose 45 mg injection just once a month via autoinjector or pre-filled syringe. Marketed as Wainua (US) and Wainzua (EU), it was FDA-approved in December 2023 for the polyneuropathy of hereditary ATTR amyloidosis (ATTRv-PN) on the strength of the NEURO-TTRansform trial, and is now approved in more than 20 countries. Eplontersen is the antisense (ASO) counterpart to the siRNA drug vutrisiran (Amvuttra): both silence TTR, and both were tested in ATTR cardiomyopathy - but where vutrisiran's HELIOS-B trial succeeded on top of a stabilizer background, eplontersen's much larger CARDIO-TTRansform cardiomyopathy trial missed its primary endpoint in July 2026, with a benefit seen only in the prespecified monotherapy subgroup. It is a GalNAc-ASO sibling of Ionis's olezarsen and pelacarsen and the second-generation successor to the earlier, non-GalNAc TTR antisense drug inotersen (Tegsedi). Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection Disease Modification: https://peptrackerpro.com/benefits/disease-modification Rare Disease Treatment: https://peptrackerpro.com/benefits/rare-disease-treatment Cardiovascular: https://peptrackerpro.com/benefits/cardiovascular View Details: https://peptrackerpro.com/peptides/eplontersen \+ Compare: https://peptrackerpro.com/compare?select=eplontersen Track in App: https://app.peptrackerpro.com/?add=eplontersen ### Inclisiran High Evidence An approved, twice-yearly subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Novartis (originally discovered by Alnylam) that lowers LDL cholesterol by silencing PCSK9 (proprotein convertase subtilisin/kexin type 9), the liver protein that destroys LDL receptors. By switching off PCSK9 production inside hepatocytes, inclisiran leaves more LDL receptors on the liver surface to pull LDL cholesterol out of the blood - achieving roughly a 50% LDL reduction with an injection given only twice a year after a loading dose. Marketed as Leqvio, it was the first siRNA medicine approved for a chronic cardiovascular condition: the EU cleared it in December 2020 and the FDA in December 2021, and in July 2025 the FDA expanded the U.S. label to first-line monotherapy, dropping the requirement that it be added on top of a statin. Its Phase 3 ORION-9, ORION-10 and ORION-11 trials established the LDL benefit; a large cardiovascular outcomes program (VICTORION-2-PREVENT and others) is still running to test whether that LDL lowering prevents heart attacks and strokes. Inclisiran is the approved, real-world proof-of-concept for the GalNAc-siRNA cardiometabolic platform that newer investigational agents like zodasiran, solbinsiran, olpasiran and plozasiran build on. View Details: https://peptrackerpro.com/peptides/inclisiran \+ Compare: https://peptrackerpro.com/compare?select=inclisiran Track in App: https://app.peptrackerpro.com/?add=inclisiran ### Lepodisiran Medium Evidence An investigational, long-duration injectable small interfering RNA (siRNA) from Eli Lilly that lowers lipoprotein(a) [Lp(a)] by nearly 94% by silencing the LPA gene in the liver. A single dose keeps Lp(a) suppressed for a year or more, and its Phase 3 ACCLAIM-Lp(a) trial (~12,500 patients) is the first Lp(a) outcomes trial to include people who have not yet had a cardiovascular event. View Details: https://peptrackerpro.com/peptides/lepodisiran \+ Compare: https://peptrackerpro.com/compare?select=lepodisiran Track in App: https://app.peptrackerpro.com/?add=lepodisiran ### Muvalaplin Medium Evidence The first oral, small-molecule inhibitor of lipoprotein(a) [Lp(a)] formation, from Eli Lilly. Instead of silencing a gene, muvalaplin is a once-daily pill that physically blocks apolipoprotein(a) from binding apolipoprotein B — the first step in building an Lp(a) particle. In its Phase 2 KRAKEN trial (published in JAMA, 2024) it cut Lp(a) by up to ~86% (placebo-adjusted) and, as of 2026, is the only Lp(a)-lowering drug that is both oral and already enrolling a large Phase 3 cardiovascular outcomes trial (MOVE-Lp(a)). View Details: https://peptrackerpro.com/peptides/muvalaplin \+ Compare: https://peptrackerpro.com/compare?select=muvalaplin Track in App: https://app.peptrackerpro.com/?add=muvalaplin ### Obicetrapib Medium Evidence An investigational once-daily oral, highly selective CETP (cholesteryl ester transfer protein) inhibitor from NewAmsterdam Pharma (European partner Menarini) that lowers LDL cholesterol and lipoprotein(a) [Lp(a)] in a single pill. Unlike the failed first-generation CETP inhibitors, obicetrapib is valued for LDL and Lp(a) lowering rather than HDL raising. In Phase 3 it cut LDL-C by about a third as monotherapy (BROADWAY) and by roughly half combined with ezetimibe (TANDEM), and reduced Lp(a) by ~33% - published in NEJM and The Lancet (2025). It received a positive EMA CHMP opinion in July 2026 (as Ubeslo and Evlarco), with the PREVAIL cardiovascular outcomes trial due to report in 2026. View Details: https://peptrackerpro.com/peptides/obicetrapib \+ Compare: https://peptrackerpro.com/compare?select=obicetrapib Track in App: https://app.peptrackerpro.com/?add=obicetrapib ### Olezarsen High Evidence An FDA-approved subcutaneous antisense oligonucleotide (ASO) from Ionis Pharmaceuticals, branded Tryngolza, that lowers triglycerides by silencing the messenger RNA for apolipoprotein C-III (apoC-III). Self-injected once a month, it was the first-ever therapy approved for familial chylomicronemia syndrome (FCS) on December 19, 2024, and on June 24, 2026 it became the first and only treatment approved to reduce both triglycerides and the risk of acute pancreatitis in the far larger severe hypertriglyceridemia (sHTG) population. View Details: https://peptrackerpro.com/peptides/olezarsen \+ Compare: https://peptrackerpro.com/compare?select=olezarsen Track in App: https://app.peptrackerpro.com/?add=olezarsen ### Olpasiran Medium Evidence An investigational, once-every-12-weeks injectable small interfering RNA (siRNA) from Amgen that lowers lipoprotein(a) [Lp(a)] by up to ~97% by silencing the LPA gene in the liver. Its Phase 3 OCEAN(a)-Outcomes cardiovascular outcomes trial (~7,000 patients) is one of the pivotal readouts — due December 2026 — that will help decide whether lowering Lp(a) prevents heart attacks and strokes. View Details: https://peptrackerpro.com/peptides/olpasiran \+ Compare: https://peptrackerpro.com/compare?select=olpasiran Track in App: https://app.peptrackerpro.com/?add=olpasiran ### Pelacarsen Medium Evidence A first-in-class, once-monthly injectable antisense oligonucleotide (ASO) from Ionis and Novartis that lowers lipoprotein(a) [Lp(a)] by shutting down apolipoprotein(a) production in the liver. Its pivotal Lp(a)HORIZON trial (8,323 patients) is the first-ever cardiovascular outcomes trial for any Lp(a)-lowering drug, with a landmark topline readout due in 2026. View Details: https://peptrackerpro.com/peptides/pelacarsen \+ Compare: https://peptrackerpro.com/compare?select=pelacarsen Track in App: https://app.peptrackerpro.com/?add=pelacarsen ### Plozasiran High Evidence An approved subcutaneous RNA interference (RNAi) therapy from Arrowhead Pharmaceuticals, branded Redemplo, that silences the gene for apolipoprotein C-III (apoC-III) to lower triglycerides. Given once every three months, it cut triglycerides by roughly 80% in familial chylomicronemia syndrome (FCS) and sharply reduced acute pancreatitis events. The FDA approved it on November 18, 2025 for FCS, and Phase 3 SHASTA-3 and SHASTA-4 (reported July 2026) extended those results to the far larger severe hypertriglyceridemia population. View Details: https://peptrackerpro.com/peptides/plozasiran \+ Compare: https://peptrackerpro.com/compare?select=plozasiran Track in App: https://app.peptrackerpro.com/?add=plozasiran ### Solbinsiran Medium Evidence An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Eli Lilly that lowers atherogenic lipids by silencing ANGPTL3 (angiopoietin-like protein 3), a liver-made brake on the fat-clearing enzymes lipoprotein lipase and endothelial lipase. By switching off ANGPTL3 production in the liver, solbinsiran simultaneously reduces both triglyceride-rich remnant particles and LDL cholesterol - the two lipid drivers of atherosclerotic cardiovascular disease. In the Phase 2 PROLONG-ANG3 trial (The Lancet, 2025; 205 adults with mixed dyslipidemia on statins), the 400 mg dose given only twice, three months apart, lowered apolipoprotein B (apoB) by a placebo-adjusted ~14% at day 180, with reductions sustained to day 270 and a ~28% fall in liver fat. Designed for infrequent dosing and built to avoid the liver toxicity that ended earlier ANGPTL3 antisense drugs, solbinsiran is positioned as the foundation for a planned Phase 3 cardiovascular outcomes program. View Details: https://peptrackerpro.com/peptides/solbinsiran \+ Compare: https://peptrackerpro.com/compare?select=solbinsiran Track in App: https://app.peptrackerpro.com/?add=solbinsiran ### Vutrisiran High Evidence An approved, quarterly (once-every-three-months) subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Alnylam that treats transthyretin-mediated (ATTR) amyloidosis by silencing the TTR gene in the liver. Transthyretin is a liver-made transport protein that can misfold and pile up as amyloid deposits in nerves and, critically, the heart; vutrisiran uses RNA interference (RNAi) to degrade both mutant and wild-type TTR messenger RNA before the protein is made, lowering circulating TTR by roughly 80% and starving the amyloid of its raw material. Marketed as Amvuttra, it was first FDA-approved in June 2022 for the polyneuropathy of hereditary ATTR amyloidosis (HELIOS-A), and in March 2025 the FDA expanded the label to ATTR cardiomyopathy (ATTR-CM) of wild-type or hereditary disease - making vutrisiran the first RNAi therapeutic shown to reduce cardiovascular death and cardiovascular events, on the strength of the HELIOS-B outcomes trial. It shares the exact GalNAc-siRNA delivery platform that underlies the cardiometabolic RNAi medicine inclisiran and the investigational agents olpasiran, lepodisiran, zerlasiran, zilebesiran, zodasiran, solbinsiran and plozasiran, and it is the direct successor to Alnylam's earlier intravenous TTR siRNA patisiran (Onpattro). Cardiovascular: https://peptrackerpro.com/benefits/cardiovascular Neuroprotection: https://peptrackerpro.com/benefits/neuroprotection Disease Modification: https://peptrackerpro.com/benefits/disease-modification Rare Disease Treatment: https://peptrackerpro.com/benefits/rare-disease-treatment View Details: https://peptrackerpro.com/peptides/vutrisiran \+ Compare: https://peptrackerpro.com/compare?select=vutrisiran Track in App: https://app.peptrackerpro.com/?add=vutrisiran ### Zerlasiran Medium Evidence An investigational, long-acting injectable small interfering RNA (siRNA) from Silence Therapeutics that lowers lipoprotein(a) [Lp(a)] by more than 80% by silencing the LPA gene in the liver. Dosed only every 16–24 weeks, it produced durable ~90% reductions in its Phase 2 ALPACAR-360 trial (published in JAMA, 2024); as of 2026 the company is seeking a partner before starting its Phase 3 cardiovascular outcomes study. View Details: https://peptrackerpro.com/peptides/zerlasiran \+ Compare: https://peptrackerpro.com/compare?select=zerlasiran Track in App: https://app.peptrackerpro.com/?add=zerlasiran ### Zilebesiran Medium Evidence An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Alnylam Pharmaceuticals and Roche/Genentech that lowers blood pressure by silencing angiotensinogen (AGT), the single upstream precursor of the renin-angiotensin-aldosterone system (RAAS). Designed for dosing as infrequently as once or twice a year, it is the first RNА interference (RNAi) therapeutic developed for hypertension. In Phase 2 KARDIA-1 and KARDIA-2 trials it produced durable, clinically meaningful reductions in systolic blood pressure sustained for up to 6 months from a single dose, and in 2025 it advanced into the large Phase 3 ZENITH cardiovascular outcomes trial. Cardiovascular: https://peptrackerpro.com/benefits/cardiovascular Disease Modification: https://peptrackerpro.com/benefits/disease-modification View Details: https://peptrackerpro.com/peptides/zilebesiran \+ Compare: https://peptrackerpro.com/compare?select=zilebesiran Track in App: https://app.peptrackerpro.com/?add=zilebesiran ### ARO-INHBE Low Evidence An investigational RNA-interference (RNAi) therapeutic from Arrowhead Pharmaceuticals designed to treat obesity by silencing a fat-storage gene in the liver. ARO-INHBE is a GalNAc-conjugated small interfering RNA (siRNA) that reduces hepatic expression of the INHBE gene and its secreted product, the hepatokine Activin E. INHBE is a genetically validated target: people who naturally carry rare loss-of-function variants in INHBE have a healthier (less abdominal) fat distribution and a lower risk of type 2 diabetes, suggesting that lowering Activin E with a drug could reproduce that protective metabolic profile. In an ongoing Phase 1/2a trial (AROINHBE-1001, NCT06700538), a single subcutaneous dose reduced serum Activin E by up to about 94%, and monotherapy reduced visceral fat by roughly 10-16% while modestly increasing lean tissue. Most strikingly, when added to the incretin drug tirzepatide in obese patients with type 2 diabetes, ARO-INHBE roughly doubled weight loss (-9.4% versus -4.8% at week 16) and roughly tripled reductions in visceral, total, and liver fat versus tirzepatide alone. These are small, early, interim results (as few as 3-4 participants per combination arm) - not proof of durable or long-term benefit. ARO-INHBE is investigational, is not approved anywhere, and is not a supplement or research chemical; it is studied only in clinical trials. Fat Loss (https://peptrackerpro.com/benefits/fat-loss)Body Composition (https://peptrackerpro.com/benefits/body-composition)Weight Management (https://peptrackerpro.com/benefits/weight-management)Metabolism (https://peptrackerpro.com/benefits/metabolism)+1 more View Details: https://peptrackerpro.com/peptides/aro-inhbe \+ Compare: https://peptrackerpro.com/compare?select=aro-inhbe Track in App: https://app.peptrackerpro.com/?add=aro-inhbe ## Structured data ```json [ { "@context": "https://schema.org", "@type": "Organization", "name": "PepTracker Pro", "url": "https://peptrackerpro.com", "logo": "https://peptrackerpro.com/favicon.png", "description": "Evidence-based educational resource dedicated to improving peptide research literacy.", "contactPoint": { "@type": "ContactPoint", "email": "hello@peptrackerpro.com", "contactType": "customer support" }, "sameAs": [] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "Zodasiran", "description": "An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Arrowhead Pharmaceuticals that lowers atherogenic lipids by silencing ANGPTL3 (angiopoietin-like protein 3), a liver-made regulator of fat metabolism. By switching off ANGPTL3 production, zodasiran deeply reduces triglycerides, remnant cholesterol and LDL cholesterol through a pathway that does not depend on the LDL receptor - making it especially relevant for people, such as those with homozygous familial hypercholesterolemia (HoFH), whose LDL receptors barely work. In the Phase 2b ARCHES-2 trial (NEJM 2024) it produced durable, dose-dependent reductions in triglycerides, remnant cholesterol and ANGPTL3, and in the Phase 2 GATEWAY study it lowered LDL cholesterol by about 40% in HoFH. 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An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Arrowhead Pharmaceuticals that lowers atherogenic lipids by silencing ANGPTL3 (angiopoietin-like protein 3), a liver-made regulator of fat metabolism. By switching off ANGPTL3 production, zodasiran deeply reduces triglycerides, remnant cholesterol and LDL cholesterol through a pathway that does not depend on the LDL receptor - making it especially relevant for people, such as those with homozygous familial hypercholesterolemia (HoFH), whose LDL receptors barely work. In the Phase 2b ARCHES-2 trial (NEJM 2024) it produced durable, dose-dependent reductions in triglycerides, remnant cholesterol and ANGPTL3, and in the Phase 2 GATEWAY study it lowered LDL cholesterol by about 40% in HoFH. It is now in the Phase 3 YOSEMITE trial in HoFH, which completed enrollment in July 2026." } }, { "@type": "Question", "name": "Patients with high triglycerides, remnant cholesterol or mixed hyperlipidemia interested in an infrequent injection rather than daily pills?", "acceptedAnswer": { "@type": "Answer", "text": "Zodasiran is a research peptide studied in preclinical models. An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Arrowhead Pharmaceuticals that lowers atherogenic lipids by silencing ANGPTL3 (angiopoietin-like protein 3), a liver-made regulator of fat metabolism. By switching off ANGPTL3 production, zodasiran deeply reduces triglycerides, remnant cholesterol and LDL cholesterol through a pathway that does not depend on the LDL receptor - making it especially relevant for people, such as those with homozygous familial hypercholesterolemia (HoFH), whose LDL receptors barely work. In the Phase 2b ARCHES-2 trial (NEJM 2024) it produced durable, dose-dependent reductions in triglycerides, remnant cholesterol and ANGPTL3, and in the Phase 2 GATEWAY study it lowered LDL cholesterol by about 40% in HoFH. It is now in the Phase 3 YOSEMITE trial in HoFH, which completed enrollment in July 2026." } }, { "@type": "Question", "name": "Clinicians and researchers following ANGPTL3-targeted therapies and comparing siRNA (zodasiran) with the ANGPTL3 antibody evinacumab or antisense approaches?", "acceptedAnswer": { "@type": "Answer", "text": "Zodasiran is a research peptide studied in preclinical models. An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Arrowhead Pharmaceuticals that lowers atherogenic lipids by silencing ANGPTL3 (angiopoietin-like protein 3), a liver-made regulator of fat metabolism. By switching off ANGPTL3 production, zodasiran deeply reduces triglycerides, remnant cholesterol and LDL cholesterol through a pathway that does not depend on the LDL receptor - making it especially relevant for people, such as those with homozygous familial hypercholesterolemia (HoFH), whose LDL receptors barely work. In the Phase 2b ARCHES-2 trial (NEJM 2024) it produced durable, dose-dependent reductions in triglycerides, remnant cholesterol and ANGPTL3, and in the Phase 2 GATEWAY study it lowered LDL cholesterol by about 40% in HoFH. It is now in the Phase 3 YOSEMITE trial in HoFH, which completed enrollment in July 2026." } }, { "@type": "Question", "name": "People tracking RNA interference (RNAi) and GalNAc-siRNA cardiometabolic medicines such as olpasiran, lepodisiran, zerlasiran, plozasiran, olezarsen and zilebesiran?", "acceptedAnswer": { "@type": "Answer", "text": "Zodasiran is a research peptide studied in preclinical models. An investigational subcutaneous GalNAc-conjugated small interfering RNA (siRNA) from Arrowhead Pharmaceuticals that lowers atherogenic lipids by silencing ANGPTL3 (angiopoietin-like protein 3), a liver-made regulator of fat metabolism. By switching off ANGPTL3 production, zodasiran deeply reduces triglycerides, remnant cholesterol and LDL cholesterol through a pathway that does not depend on the LDL receptor - making it especially relevant for people, such as those with homozygous familial hypercholesterolemia (HoFH), whose LDL receptors barely work. In the Phase 2b ARCHES-2 trial (NEJM 2024) it produced durable, dose-dependent reductions in triglycerides, remnant cholesterol and ANGPTL3, and in the Phase 2 GATEWAY study it lowered LDL cholesterol by about 40% in HoFH. It is now in the Phase 3 YOSEMITE trial in HoFH, which completed enrollment in July 2026." } } ] } ] ```