--- title: "Lepodisiran | PepTracker Pro" url: https://peptrackerpro.com/peptides/lepodisiran description: "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." 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) # 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. Aliases LY3819469 +3 more Evidence Medium Evidence Last Updated 2026-08-07 Reading Time 5 min ## What It Is Lepodisiran (LY3819469) is a GalNAc-conjugated small interfering RNA (siRNA) being developed by Eli Lilly to lower lipoprotein(a) — written Lp(a) — a genetically determined, independent, causal risk factor for heart attack, stroke, peripheral artery disease, and calcific aortic valve stenosis that affects roughly one in five people and cannot be meaningfully lowered by diet, exercise, statins, or PCSK9 inhibitors. Like the antisense oligonucleotide pelacarsen and the siRNAs olpasiran and zerlasiran, lepodisiran attacks the same target, but it is engineered for exceptional duration: a sugar tag (GalNAc, N-acetylgalactosamine) delivers the double-stranded siRNA to liver cells, where it loads the RISC (RNA-induced silencing complex) to catalytically degrade the messenger RNA for apolipoprotein(a) — the LPA gene product that defines the Lp(a) particle. Its chemistry, including a stabilizing tetraloop that joins the two RNA strands, gives it an unusually long duration of action, so that a single subcutaneous injection can keep Lp(a) suppressed for a year or more. In the Phase 2 ALPACA trial (320 adults with elevated Lp(a); doses of 16, 96, or 400 mg), the 400 mg dose lowered Lp(a) by 93.9% (placebo-adjusted, time-averaged over days 60–180) — the primary endpoint — with the 96 mg and 16 mg doses producing 75.2% and 40.8% reductions; the effect was strikingly durable, still around 91% below baseline at roughly one year and about 74% below baseline at 1.5 years after a single dose, with no serious drug-related adverse events. Those results were presented at the American College of Cardiology 2025 Scientific Sessions and published in the New England Journal of Medicine in 2025. The pivotal Phase 3 ACCLAIM-Lp(a) trial (NCT06292013) enrolled about 12,500 patients randomized 1:1 to lepodisiran or placebo on top of standard care, and is notable as the first Lp(a)-lowering outcomes trial to include primary-prevention patients (people at risk for a first cardiovascular event) alongside secondary-prevention patients with established atherosclerotic cardiovascular disease. Dosing is infrequent — the first three subcutaneous doses are given six months apart, then every 12 months thereafter. It is an event-driven study of roughly 4.75 years testing whether lowering Lp(a) reduces major adverse cardiovascular events, with completion expected around 2029. Lilly has also begun a coronary-plaque imaging trial (NCT07613294). Lepodisiran is investigational and not approved anywhere; it is a clinical-stage prescription medicine, not a supplement or research chemical. Also known as: LY3819469, Lp(a)-lowering siRNA, apolipoprotein(a) siRNA, long-duration Lp(a) siRNA ## Regulatory Status Investigational — not approved Lepodisiran is not approved for any use anywhere. It is being evaluated in the pivotal Phase 3 ACCLAIM-Lp(a) cardiovascular outcomes trial (NCT06292013; ~12,500 patients randomized 1:1 to lepodisiran or placebo, including both primary- and secondary-prevention patients with elevated Lp(a)), an event-driven study of roughly 4.75 years with completion expected around 2029. Subcutaneous dosing: the first three doses are six months apart, then every 12 months. The primary endpoint is a composite of major adverse cardiovascular events. A coronary-plaque imaging trial (NCT07613294) is also underway. Developed by Eli Lilly. Effective: 2026 View FDA Source (https://clinicaltrials.gov/study/NCT06292013) ## Why Researchers Study It Lepodisiran is one of a small handful of therapies that can do something no established drug can: dramatically and durably lower lipoprotein(a), an inherited cardiovascular risk factor that statins and PCSK9 inhibitors barely touch. Its distinguishing feature within the Lp(a)-lowering class is duration — a single injection can suppress Lp(a) for a year or more — raising the prospect of once- or twice-yearly dosing. Researchers also study it because its Phase 3 ACCLAIM-Lp(a) trial is the first Lp(a) outcomes trial to enroll primary-prevention patients, meaning it could speak not only to people who have already had a cardiovascular event but to the much larger population born with high Lp(a) who have not. Like the rest of the class, it is a key test of the field's central, still-unproven hypothesis — that lowering Lp(a) actually prevents heart attacks and strokes. ## Proposed Mechanisms - GalNAc-conjugated small interfering RNA (siRNA) delivered selectively to hepatocytes - Loads into the RNA-induced silencing complex (RISC), which catalytically cleaves apolipoprotein(a) [LPA] messenger RNA in the liver - Suppresses apo(a) synthesis so the liver assembles far fewer Lp(a) particles, lowering circulating Lp(a) by nearly 94% at the top dose - Stabilizing chemistry (including a tetraloop joining the two RNA strands) gives an unusually long duration, so a single dose can suppress Lp(a) for a year or more - Aims to reduce the atherogenic, pro-inflammatory, and pro-thrombotic cardiovascular risk carried by Lp(a) independent of LDL cholesterol ## Evidence Snapshot Medium Evidence Low Medium High | Study Type | Model | Outcome | Link | | --- | --- | --- | --- | | Phase 2 (ALPACA, dose-finding, NCT05565742) | 320 adults with elevated Lp(a); lepodisiran 16/96/400 mg subcutaneous (dosed at day 1 and day 180) vs placebo | Primary endpoint met: the 400 mg dose lowered Lp(a) by 93.9% (placebo-adjusted, time-averaged days 60–180); 96 mg and 16 mg produced 75.2% and 40.8% reductions. No serious drug-related adverse events. Published in NEJM (2025) | Source: https://www.nejm.org/doi/abs/10.1056/NEJMoa2415818 | | Phase 2 (durability of single dose) | ALPACA participants followed after a single 400 mg injection | Reductions were exceptionally durable: Lp(a) remained ~91% below baseline at roughly one year and ~74% below baseline at 1.5 years after a single dose, supporting infrequent (once- or twice-yearly) dosing | Source: https://www.nejm.org/doi/abs/10.1056/NEJMoa2415818 | | Phase 3 (ACCLAIM-Lp(a), cardiovascular outcomes, NCT06292013) | ~12,500 adults with elevated Lp(a), including both primary- and secondary-prevention patients; lepodisiran vs placebo (first 3 doses 6 months apart, then every 12 months) — global, randomized, double-blind, placebo-controlled | Tests whether lowering Lp(a) reduces major adverse cardiovascular events. Event-driven, ~4.75 years; first Lp(a) outcomes trial to include primary prevention; completion expected ~2029 | Source: https://clinicaltrials.gov/study/NCT06292013 | ## 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 Lepodisiran? Track it, set reminders, and keep notes in the free app. Track in App (https://app.peptrackerpro.com/?add=lepodisiran) ## Safety & Cautions - Investigational — not approved for any use anywhere; whether its ~94% Lp(a) lowering translates into fewer cardiovascular events is exactly what the ongoing ACCLAIM-Lp(a) trial (completion ~2029) is designed to test - Robust Lp(a) reduction is well established, but cardiovascular outcome benefit has not yet been demonstrated for any Lp(a)-lowering drug - A prescription clinical-stage medicine given by subcutaneous injection under medical supervision — not a supplement, nootropic, or research chemical - Any 'lepodisiran' or 'LY3819469' offered by a vendor is unverified and not a legitimate source of this investigational medicine - Targets Lp(a) and is NOT interchangeable with LDL-lowering statins or PCSK9 inhibitors, which do not meaningfully lower Lp(a) ## Comparisons See how Lepodisiran compares to related peptides: Lepodisiran vs Eplontersen: https://peptrackerpro.com/compare/lepodisiran-vs-eplontersen Lepodisiran vs Inclisiran: https://peptrackerpro.com/compare/lepodisiran-vs-inclisiran Lepodisiran vs Muvalaplin: https://peptrackerpro.com/compare/lepodisiran-vs-muvalaplin Lepodisiran vs Obicetrapib: https://peptrackerpro.com/compare/lepodisiran-vs-obicetrapib Lepodisiran vs Olezarsen: https://peptrackerpro.com/compare/lepodisiran-vs-olezarsen Lepodisiran vs Olpasiran: https://peptrackerpro.com/compare/lepodisiran-vs-olpasiran Lepodisiran vs Pelacarsen: https://peptrackerpro.com/compare/lepodisiran-vs-pelacarsen Lepodisiran vs Plozasiran: https://peptrackerpro.com/compare/lepodisiran-vs-plozasiran Lepodisiran vs Solbinsiran: https://peptrackerpro.com/compare/lepodisiran-vs-solbinsiran Lepodisiran vs Vutrisiran: https://peptrackerpro.com/compare/lepodisiran-vs-vutrisiran Lepodisiran vs WVE-007: https://peptrackerpro.com/compare/lepodisiran-vs-wve-007 Lepodisiran vs Zerlasiran: https://peptrackerpro.com/compare/lepodisiran-vs-zerlasiran Lepodisiran vs Zilebesiran: https://peptrackerpro.com/compare/lepodisiran-vs-zilebesiran Lepodisiran vs Ziltivekimab: https://peptrackerpro.com/compare/lepodisiran-vs-ziltivekimab Lepodisiran vs Zodasiran: https://peptrackerpro.com/compare/lepodisiran-vs-zodasiran ## Calculator Tools Use our research tools to explore dosing and reconstitution data: Reconstitution Calculator: https://peptrackerpro.com/calculators ## Citations 1. [1] Nissen SE et al. — Lepodisiran, A Long-Duration Small Interfering RNA Targeting Lipoprotein(a) (ALPACA Phase 2), New England Journal of Medicine (2025) PubMed (https://www.nejm.org/doi/abs/10.1056/NEJMoa2415818) 2. [2] ACCLAIM-Lp(a) — A Study to Investigate the Effect of Lepodisiran on the Reduction of Major Adverse Cardiovascular Events (ClinicalTrials.gov NCT06292013) PubMed (https://clinicaltrials.gov/study/NCT06292013) 3. [3] Lilly's lepodisiran reduced Lp(a) by nearly 94% at the highest tested dose — Eli Lilly and Company (ACC 2025) PubMed (https://investor.lilly.com/news-releases/news-release-details/lillys-lepodisiran-reduced-levels-genetically-inherited-heart) 4. [4] ALPACA — A Study of LY3819469 (Lepodisiran) in Participants With Elevated Lp(a) (ClinicalTrials.gov NCT05565742) PubMed (https://clinicaltrials.gov/study/NCT05565742) 5. [5] Lipoprotein(a): An Independent Risk Factor for CV Disease — American College of Cardiology PubMed (https://www.acc.org/latest-in-cardiology/articles/2025/12/01/01/feature-lipoprotein-a) ### Keep researching in the app - Log Lepodisiran 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=lepodisiran 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 ### 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 ### WVE-007 Low Evidence WVE-007 is Wave Life Sciences' investigational GalNAc-conjugated siRNA that silences the liver gene INHBE to lower the hepatokine Activin E, aiming to produce muscle-sparing fat loss. In the Phase 1 INLIGHT trial a single subcutaneous dose reduced visceral and total fat while preserving or increasing lean mass, with durable target knockdown that could support once- or twice-yearly dosing. Weight Management: https://peptrackerpro.com/benefits/weight-management Metabolism: https://peptrackerpro.com/benefits/metabolism Fat Loss: https://peptrackerpro.com/benefits/fat-loss Muscle Preservation: https://peptrackerpro.com/benefits/muscle-preservation View Details: https://peptrackerpro.com/peptides/wve-007 \+ Compare: https://peptrackerpro.com/compare?select=wve-007 Track in App: https://app.peptrackerpro.com/?add=wve-007 ### 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 ### Ziltivekimab Medium Evidence An investigational, fully human monoclonal antibody that neutralizes the pro-inflammatory cytokine interleukin-6 (IL-6) to test whether lowering vascular inflammation - independently of cholesterol - can prevent heart attacks, strokes and cardiovascular death. Given as a low-volume, once-monthly 15 mg subcutaneous injection (half-life ~57 days), ziltivekimab was originally developed by Corvidia Therapeutics and acquired by Novo Nordisk in 2020 for up to $2.1 billion. It is the flagship clinical test of the 'residual inflammatory risk' hypothesis that grew out of the CANTOS trial of the IL-1 beta antibody canakinumab: the idea that many high-risk patients keep having cardiovascular events because of ongoing inflammation (marked by high-sensitivity C-reactive protein, hsCRP) even when LDL cholesterol is well controlled. In the Phase 2 RESCUE trial ziltivekimab cut hsCRP by up to ~92%, and it advanced into three large Phase 3 cardiovascular outcomes trials - ZEUS, HERMES and ARTEMIS. On July 31, 2026, Novo Nordisk announced that the pivotal ZEUS trial (>6,300 patients with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation) MISSED its primary endpoint: despite clear target engagement (large falls in free IL-6 and hsCRP), ziltivekimab did not reduce major adverse cardiovascular events versus placebo (hazard ratio 0.99, 95% CI 0.88-1.11). The heart-failure trial HERMES and the post-heart-attack trial ARTEMIS continue, with readouts expected in the first half of 2027. Ziltivekimab is a prescription-stage investigational biologic - it is not approved anywhere and is not a supplement or research chemical. Inflammation: https://peptrackerpro.com/benefits/inflammation Cardiovascular: https://peptrackerpro.com/benefits/cardiovascular Kidney Health: https://peptrackerpro.com/benefits/kidney-health Cholesterol Management: https://peptrackerpro.com/benefits/cholesterol-management View Details: https://peptrackerpro.com/peptides/ziltivekimab \+ Compare: https://peptrackerpro.com/compare?select=ziltivekimab Track in App: https://app.peptrackerpro.com/?add=ziltivekimab ### 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. View Details: https://peptrackerpro.com/peptides/zodasiran \+ Compare: https://peptrackerpro.com/compare?select=zodasiran Track in App: https://app.peptrackerpro.com/?add=zodasiran ## 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": "Lepodisiran", "description": "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.", "url": "https://peptrackerpro.com/peptides/lepodisiran", "lastReviewed": "2026-08-07", "reviewedBy": { "@type": "Organization", "name": "PepTracker Pro Research Team", "url": "https://peptrackerpro.com" }, "isPartOf": { "@type": "WebSite", "name": "PepTracker Pro", "url": "https://peptrackerpro.com" } }, { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://peptrackerpro.com" }, { "@type": "ListItem", "position": 2, "name": "Peptides", "item": "https://peptrackerpro.com/peptides" }, { "@type": "ListItem", "position": 3, "name": "Lepodisiran", "item": "https://peptrackerpro.com/peptides/lepodisiran" } ] }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "People who have learned they have high lipoprotein(a) and want to know which treatments are furthest along?", "acceptedAnswer": { "@type": "Answer", "text": "Lepodisiran is a research peptide studied in preclinical models. 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." } }, { "@type": "Question", "name": "Those at inherited cardiovascular risk who have not yet had an event and want to know whether trials include primary prevention?", "acceptedAnswer": { "@type": "Answer", "text": "Lepodisiran is a research peptide studied in preclinical models. 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." } }, { "@type": "Question", "name": "Clinicians and researchers tracking the pivotal Lp(a)-lowering cardiovascular outcomes trials?", "acceptedAnswer": { "@type": "Answer", "text": "Lepodisiran is a research peptide studied in preclinical models. 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." } }, { "@type": "Question", "name": "Those comparing lepodisiran (a long-duration siRNA) with olpasiran and zerlasiran (siRNAs) and the antisense oligonucleotide pelacarsen?", "acceptedAnswer": { "@type": "Answer", "text": "Lepodisiran is a research peptide studied in preclinical models. 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." } } ] } ] ```