--- title: "Nucresiran | PepTracker Pro" url: https://peptrackerpro.com/peptides/nucresiran description: "An investigational next-generation RNA interference (RNAi) therapeutic from Alnylam Pharmaceuticals designed to silence the transthyretin (TTR) gene and treat transthyretin amyloidosis (ATTR) - the same disease targeted by Alnylam's approved drugs patisiran and vutrisiran (Amvuttra) and by Ionis/AstraZeneca's eplontersen (Wainua/Wainzua). Nucresiran (formerly ALN-TTRsc04) is a subcutaneous GalNAc-conjugated small interfering RNA (siRNA) built on Alnylam's newer IKARIA platform, engineered for deeper, more durable knockdown of both mutant and wild-type TTR with the potential for once- or twice-yearly dosing - a substantial step beyond the current quarterly (vutrisiran) or monthly (eplontersen) schedules. In an interim Phase 1 single-ascending-dose study in 48 healthy volunteers (presented at AHA 2024), a single dose of 300 mg or higher rapidly lowered serum TTR by more than 90% by Day 15 and by more than 96% at peak (Day 29), with more than 70% reduction still present at one year after a single 300 mg dose and low patient-to-patient variability; all doses were well tolerated with no injection-site reactions and no liver safety signals. Alnylam has moved nucresiran into a Phase 3 TRITON program: TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, an open-label study using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), a large event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously once every six months. Nucresiran is investigational and not approved by the FDA, EMA or any regulator; it is studied only in clinical trials and is not a supplement or research chemical." 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) # Nucresiran Medium Evidence An investigational next-generation RNA interference (RNAi) therapeutic from Alnylam Pharmaceuticals designed to silence the transthyretin (TTR) gene and treat transthyretin amyloidosis (ATTR) - the same disease targeted by Alnylam's approved drugs patisiran and vutrisiran (Amvuttra) and by Ionis/AstraZeneca's eplontersen (Wainua/Wainzua). Nucresiran (formerly ALN-TTRsc04) is a subcutaneous GalNAc-conjugated small interfering RNA (siRNA) built on Alnylam's newer IKARIA platform, engineered for deeper, more durable knockdown of both mutant and wild-type TTR with the potential for once- or twice-yearly dosing - a substantial step beyond the current quarterly (vutrisiran) or monthly (eplontersen) schedules. In an interim Phase 1 single-ascending-dose study in 48 healthy volunteers (presented at AHA 2024), a single dose of 300 mg or higher rapidly lowered serum TTR by more than 90% by Day 15 and by more than 96% at peak (Day 29), with more than 70% reduction still present at one year after a single 300 mg dose and low patient-to-patient variability; all doses were well tolerated with no injection-site reactions and no liver safety signals. Alnylam has moved nucresiran into a Phase 3 TRITON program: TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, an open-label study using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), a large event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously once every six months. Nucresiran is investigational and not approved by the FDA, EMA or any regulator; it is studied only in clinical trials and is not a supplement or research chemical. Aliases Nucresiran +6 more Evidence Medium Evidence Last Updated 2026-09-05 Reading Time 8 min ## What It Is Nucresiran (development code ALN-TTRsc04) is Alnylam Pharmaceuticals' next-generation RNA interference (RNAi) therapeutic aimed at transthyretin amyloidosis (ATTR), a progressive and fatal disease in which misfolded transthyretin (TTR) protein deposits as amyloid in the nerves, heart and gastrointestinal tract, causing polyneuropathy, cardiomyopathy, or both. ATTR exists in two forms: hereditary ATTR (hATTR), caused by TTR gene variants and affecting roughly 50,000 people worldwide, and wild-type ATTR (wtATTR), which occurs without a gene variant and is estimated to affect 200,000-300,000 people, predominantly older men with cardiac disease. Like Alnylam's approved TTR silencers patisiran (Onpattro) and vutrisiran (Amvuttra), and the antisense oligonucleotide eplontersen (Wainua/Wainzua), nucresiran works upstream of today's stabilizer drugs (such as tafamidis and acoramidis) by degrading TTR messenger RNA in the liver so that far less TTR protein - both mutant and wild-type - is made in the first place. What sets nucresiran apart is Alnylam's proprietary IKARIA platform, an enhanced-chemistry, GalNAc-conjugated subcutaneous siRNA design intended to deliver deeper and much longer-lasting gene silencing, opening the door to dosing as infrequently as once or twice a year. In an ongoing randomized, double-blind, placebo-controlled Phase 1 single-ascending-dose study, 48 healthy adults received a single subcutaneous dose of 5, 25, 100, 300, 600 or 900 mg of nucresiran (or placebo). At doses of 300 mg and above, mean serum TTR fell by more than 90% by Day 15 and reached peak reductions above 96% by Day 29; the effect was highly durable, with mean TTR still reduced by about 92-96% at six months and, for the 300 mg cohort, by more than 70% at one year (about 71% at Day 360). Reductions were remarkably consistent between patients (for example, roughly 96-98% knockdown across individuals at Day 29 in the higher-dose cohorts), and the therapy was well tolerated: most adverse events were mild, none were considered treatment-related, and there were no injection-site reactions and no liver-related safety signals at the doses tested. These data, presented at the American Heart Association Scientific Sessions 2024, led Alnylam to describe nucresiran as supporting a potential 'new paradigm' of biannual or annual dosing for ATTR. Alnylam has since launched a Phase 3 TRITON program with two pivotal studies. TRITON-PN (NCT07223203) is a global, randomized, open-label study of about 125 patients with hereditary ATTR with polyneuropathy; it uses the approved drug vutrisiran as an active comparator and is designed to show that nucresiran is superior to vutrisiran in lowering serum TTR while improving neurologic impairment, quality of life, disability, nutritional status and gait speed, with the goal of reaching patients as quickly as possible (Alnylam has targeted a launch around 2028). TRITON-CM (NCT07052903) is a much larger, event-driven cardiovascular outcomes trial in patients with ATTR cardiomyopathy - wild-type or any TTR variant, including patients on background stabilizer therapy - enrolling roughly 1,200 people and dosing nucresiran 300 mg subcutaneously once every six months, with a potential approval around 2030 if successful. Strategically, nucresiran is central to Alnylam's effort to defend and extend its TTR franchise (Amvuttra), which faces growing competition in ATTR cardiomyopathy from stabilizers such as tafamidis (Vyndaqel/Vyndamax) and acoramidis (Attruby), the gene-editing candidate NTLA-2001 (nexiguran ziclumeran), and eplontersen. If the durable, low-frequency dosing seen in Phase 1 holds up in Phase 3, nucresiran could offer patients an ATTR treatment given as seldom as once or twice a year. Important caveats remain: the efficacy data so far come from a small Phase 1 study in healthy volunteers measuring a biomarker (serum TTR), not clinical outcomes in patients; the Phase 3 program is ongoing and clinical benefit has not been demonstrated; the durability and safety of repeat dosing over years are not yet established; and nucresiran has not been approved by any regulator. It is not a supplement or a research chemical, and any product marketed as 'nucresiran' or 'ALN-TTRsc04' outside a regulated clinical trial is unverified. Also known as: Nucresiran, ALN-TTRsc04, ALN TTRsc04, Alnylam nucresiran, next-generation TTR silencer, IKARIA TTR RNAi, nucresiran injection ## Regulatory Status Investigational Not approved by the FDA, EMA or any regulator. Nucresiran (formerly ALN-TTRsc04) is an investigational next-generation GalNAc-conjugated siRNA TTR silencer from Alnylam Pharmaceuticals, built on the IKARIA platform and in Phase 3 development for transthyretin amyloidosis. The pivotal TRITON program comprises TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), an event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously every six months. Available only within clinical trials; no marketing approval anywhere as of this writing. Effective: 2026 View FDA Source (https://investors.alnylam.com/press-release?id=28541) ## Why Researchers Study It Nucresiran sits at the frontier of two important stories: the maturation of RNA interference into a mainstream class of medicines, and the fast-moving competition to treat transthyretin amyloidosis (ATTR), an underdiagnosed but increasingly recognized cause of heart failure and neuropathy in older adults. Alnylam already proved that silencing the TTR gene can change the course of ATTR with patisiran and vutrisiran, but those drugs require infusions or quarterly injections; nucresiran's appeal is that its IKARIA-platform chemistry produced roughly 90-96% TTR knockdown from a single subcutaneous dose that lasted six months to a year in early testing, raising the possibility of a highly effective treatment given only once or twice a year. Researchers are watching whether that durable biomarker effect translates into real clinical benefit in the Phase 3 TRITON-PN and TRITON-CM trials, how nucresiran stacks up against its own predecessor vutrisiran (its active comparator in TRITON-PN) and against stabilizers and gene-editing approaches, and what its consistency and clean early safety profile imply for the broader promise of low-frequency, high-potency RNAi therapeutics. ## Proposed Mechanisms - RNA interference (RNAi) gene silencing: nucresiran is a small interfering RNA (siRNA) that directs the cell's RNA-induced silencing complex to degrade transthyretin (TTR) messenger RNA in liver cells, reducing production of both mutant and wild-type TTR protein at the source. - GalNAc-conjugated subcutaneous delivery: like other modern Alnylam siRNAs, nucresiran is conjugated to N-acetylgalactosamine (GalNAc) to target uptake by liver hepatocytes (the main site of TTR synthesis) after a simple subcutaneous injection. - IKARIA platform for deep, durable knockdown: enhanced siRNA chemistry gives nucresiran greater potency and longevity than earlier TTR silencers, producing >90% knockdown by Day 15, >96% peak reduction, and sustained lowering (>70% at one year after a single 300 mg dose) that supports once- or twice-yearly dosing. - Disease modification by reducing amyloid substrate: by lowering circulating TTR, nucresiran is designed to slow or halt the formation of new amyloid deposits that damage nerves and the heart in ATTR, rather than merely stabilizing the protein as tafamidis and acoramidis do. - Low inter-patient variability: early data showed tightly clustered TTR reductions across individuals (about 96-98% at Day 29 in higher-dose cohorts), suggesting predictable, consistent silencing - a practical advantage for a chronically dosed therapy. ## Evidence Snapshot Medium Evidence Low Medium High | Study Type | Model | Outcome | Link | | --- | --- | --- | --- | | Phase 1 randomized, double-blind, placebo-controlled single-ascending-dose study (ALN-TTRsc04 / nucresiran); interim data presented at AHA Scientific Sessions 2024 | 48 healthy adult volunteers randomized 3:1 to a single subcutaneous dose of nucresiran 5, 25, 100, 300, 600 or 900 mg or placebo; primary endpoint safety, with serum TTR change and pharmacokinetics as secondary endpoints. | At doses of 300 mg and above, mean serum TTR fell >90% by Day 15 and >96% at peak (Day 29), with ~92-96% reduction sustained at six months and >70% (about 71%) still present at one year after a single 300 mg dose; low inter-patient variability (~96-98% knockdown at Day 29 in higher-dose cohorts). Well tolerated - most adverse events mild, none treatment-related, no injection-site reactions and no liver safety signals. | Source | | Phase 3 randomized, open-label, active-comparator trial - TRITON-PN (NCT07223203); ongoing | About 125 patients with hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN); participants receive nucresiran or start on the approved drug vutrisiran before switching to nucresiran, with vutrisiran as the active comparator. | Designed to demonstrate superiority of nucresiran over vutrisiran in lowering serum TTR while assessing neurologic impairment, quality of life, disability, nutritional status and gait speed. Ongoing; results not yet reported. Alnylam has targeted a potential launch around 2028. | Source | | Phase 3 event-driven cardiovascular outcomes trial - TRITON-CM (NCT07052903); ongoing | About 1,200 patients with ATTR cardiomyopathy (wild-type or any TTR variant) with confirmed cardiomyopathy, including patients on background stabilizer therapy; nucresiran dosed 300 mg subcutaneously once every six months. | Designed to evaluate cardiovascular outcomes (an event-driven design); ongoing with results not yet reported. If successful, potential regulatory approval around 2030. | Source | ## Commonly Discussed Benefits 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 Researching Nucresiran? Track it, set reminders, and keep notes in the free app. Track in App (https://app.peptrackerpro.com/?add=nucresiran) ## Safety & Cautions - Nucresiran is an investigational medicine with no marketing approval anywhere; it is not a supplement or research chemical, and any product sold as 'nucresiran' or 'ALN-TTRsc04' outside a regulated clinical trial is unverified and unsafe. - Efficacy data to date come from a small Phase 1 single-dose study in healthy volunteers and measure a biomarker (serum TTR reduction), not clinical outcomes; whether deep TTR knockdown translates into slower neuropathy progression or fewer cardiovascular events in patients is being tested in the ongoing Phase 3 TRITON trials and is not yet established. - Long-term safety and the effects of repeat dosing over years are not yet known; the reassuring tolerability so far (no injection-site reactions, no liver signals) reflects single doses in healthy adults, and TTR-lowering therapies are generally monitored for vitamin A deficiency because TTR carries retinol (vitamin A) in the blood. - Nucresiran is one of several TTR-directed and TTR-stabilizing options for ATTR (including vutrisiran, patisiran, eplontersen, tafamidis, acoramidis and the gene-editing candidate nexiguran ziclumeran); cross-trial comparisons among them are not head-to-head and can be misleading because trial designs, populations and endpoints differ. - ATTR amyloidosis is a serious, progressive disease that requires specialist diagnosis (including genetic testing for hereditary forms) and management; decisions about treatment should be made with a qualified clinician using approved therapies. - This is background information about an experimental medicine for a rare disease, not medical advice, and does not describe an approved treatment or a dosing recommendation. ## Comparisons See how Nucresiran compares to related peptides: Nucresiran vs Eplontersen: https://peptrackerpro.com/compare/nucresiran-vs-eplontersen Nucresiran vs Inclisiran: https://peptrackerpro.com/compare/nucresiran-vs-inclisiran Nucresiran vs Vutrisiran: https://peptrackerpro.com/compare/nucresiran-vs-vutrisiran Nucresiran vs Zilebesiran: https://peptrackerpro.com/compare/nucresiran-vs-zilebesiran Nucresiran vs Fitusiran: https://peptrackerpro.com/compare/nucresiran-vs-fitusiran Nucresiran vs Donidalorsen: https://peptrackerpro.com/compare/nucresiran-vs-donidalorsen ## Calculator Tools Use our research tools to explore dosing and reconstitution data: Reconstitution Calculator: https://peptrackerpro.com/calculators ## Citations 1. [1] Alnylam Announces Interim Phase 1 Data of Nucresiran (ALN-TTRsc04) Showing Rapid Knockdown of TTR that is Sustained at Six Months Following a Single Dose - Alnylam (November 17, 2024) PubMed (https://investors.alnylam.com/press-release?id=28541) 2. [2] Alnylam Announces Interim Phase 1 Data of Nucresiran (ALN-TTRsc04) - BioSpace (November 2024) PubMed (https://www.biospace.com/press-releases/alnylam-announces-interim-phase-1-data-of-nucresiran-aln-ttrsc04-showing-rapid-knockdown-of-ttr-that-is-sustained-at-six-months-following-a-single-dose) 3. [3] Alnylam Highlights Significant Pipeline Progress and Platform Innovation at R&D Day (nucresiran >95% knockdown with twice-annual dosing) - Alnylam PubMed (https://investors.alnylam.com/press-release?id=28716) 4. [4] TRITON-PN Phase 3 Study Design and Rationale Presented at the 2026 American Academy of Neurology (AAN) Meeting - Alnylam Capella PubMed (https://capella.alnylam.com/2026/04/20/aan-2026) 5. [5] TRITON-PN: A Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Hereditary Transthyretin Amyloidosis With Polyneuropathy - ClinicalTrials.gov (NCT07223203) PubMed (https://clinicaltrials.gov/study/NCT07223203) 6. [6] TRITON-CM: A Study to Evaluate Nucresiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy - ClinicalTrials.gov (NCT07052903) PubMed (https://clinicaltrials.gov/study/NCT07052903) 7. [7] About Nucresiran and the IKARIA Platform - Alnylam Pharmaceuticals PubMed (https://www.alnylam.com/alnylam-rnai-pipeline) ### Keep researching in the app - Log Nucresiran 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=nucresiran 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. Cardiovascular: https://peptrackerpro.com/benefits/cardiovascular Cholesterol Management: https://peptrackerpro.com/benefits/cholesterol-management Disease Modification: https://peptrackerpro.com/benefits/disease-modification View Details: https://peptrackerpro.com/peptides/inclisiran \+ Compare: https://peptrackerpro.com/compare?select=inclisiran Track in App: https://app.peptrackerpro.com/?add=inclisiran ### 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). View Details: https://peptrackerpro.com/peptides/vutrisiran \+ Compare: https://peptrackerpro.com/compare?select=vutrisiran Track in App: https://app.peptrackerpro.com/?add=vutrisiran ### 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 ### Fitusiran High Evidence An FDA-approved RNA-interference (RNAi) therapy for hemophilia that works by lowering a natural blood-thinning protein rather than replacing a missing clotting factor. Fitusiran (brand name Qfitlia) is a GalNAc-conjugated small interfering RNA (siRNA) that is taken up by liver cells and silences the gene for antithrombin, the body's main brake on clotting. By reducing antithrombin, fitusiran 'rebalances' hemostasis so that people with hemophilia A or B can generate enough thrombin to form stable clots and bleed less often. It was approved by the U.S. FDA on March 28, 2025 - the first siRNA (RNAi) therapy for hemophilia and the first medicine that treats hemophilia by lowering antithrombin - for routine prophylaxis in adults and children aged 12 and older with hemophilia A or B, with or without factor VIII or IX inhibitors. A key practical advantage is that it is given as an infrequent subcutaneous injection (starting once every two months, as few as about six injections per year) and works regardless of hemophilia type or inhibitor status. In the pivotal Phase 3 ATLAS trials, fitusiran reduced the annualized bleeding rate by about 90% versus on-demand treatment. Because lowering antithrombin shifts the clotting balance, fitusiran carries a boxed warning for thrombotic (clotting) events and gallbladder disease, and it is now dosed to a target antithrombin level (15-35%) to reduce clot risk. Fitusiran is a prescription biologic administered under medical supervision - not a supplement or research chemical. Hematology: https://peptrackerpro.com/benefits/hematology Rare Disease Treatment: https://peptrackerpro.com/benefits/rare-disease-treatment View Details: https://peptrackerpro.com/peptides/fitusiran \+ Compare: https://peptrackerpro.com/compare?select=fitusiran Track in App: https://app.peptrackerpro.com/?add=fitusiran ### Donidalorsen High Evidence An FDA-approved RNA-targeted therapy that prevents hereditary angioedema (HAE) attacks by turning down production of a single blood protein rather than blocking it after it forms. Donidalorsen (brand name Dawnzera) is a GalNAc-conjugated antisense oligonucleotide (ASO) taken up by liver cells, where it binds the messenger RNA for prekallikrein (the gene KLKB1) and triggers its degradation, lowering circulating prekallikrein. Because prekallikrein sits at the top of the kallikrein-kinin cascade that generates bradykinin - the peptide that drives the swelling of HAE - reducing it prevents the runaway bradykinin surges responsible for painful, sometimes life-threatening attacks. It was approved by the U.S. FDA on August 21, 2025 as the first and only RNA-targeted prophylactic medicine for HAE, for routine prevention of attacks in adults and children aged 12 and older. It is given as an 80 mg subcutaneous self-injection by autoinjector once every four weeks, with the option to move to once every eight weeks in well-controlled patients. In the pivotal Phase 3 OASIS-HAE trial, donidalorsen reduced monthly HAE attacks by about 81% versus placebo over 24 weeks, and in the OASISplus switch study most patients who moved from other long-term prophylaxis preferred donidalorsen. Donidalorsen is a prescription biologic developed by Ionis Pharmaceuticals and administered under specialist care - not a supplement or research chemical. Immune Modulation: https://peptrackerpro.com/benefits/immune-modulation Rare Disease Treatment: https://peptrackerpro.com/benefits/rare-disease-treatment View Details: https://peptrackerpro.com/peptides/donidalorsen \+ Compare: https://peptrackerpro.com/compare?select=donidalorsen Track in App: https://app.peptrackerpro.com/?add=donidalorsen ## 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": "Nucresiran", "description": "An investigational next-generation RNA interference (RNAi) therapeutic from Alnylam Pharmaceuticals designed to silence the transthyretin (TTR) gene and treat transthyretin amyloidosis (ATTR) - the same disease targeted by Alnylam's approved drugs patisiran and vutrisiran (Amvuttra) and by Ionis/AstraZeneca's eplontersen (Wainua/Wainzua). Nucresiran (formerly ALN-TTRsc04) is a subcutaneous GalNAc-conjugated small interfering RNA (siRNA) built on Alnylam's newer IKARIA platform, engineered for deeper, more durable knockdown of both mutant and wild-type TTR with the potential for once- or twice-yearly dosing - a substantial step beyond the current quarterly (vutrisiran) or monthly (eplontersen) schedules. In an interim Phase 1 single-ascending-dose study in 48 healthy volunteers (presented at AHA 2024), a single dose of 300 mg or higher rapidly lowered serum TTR by more than 90% by Day 15 and by more than 96% at peak (Day 29), with more than 70% reduction still present at one year after a single 300 mg dose and low patient-to-patient variability; all doses were well tolerated with no injection-site reactions and no liver safety signals. Alnylam has moved nucresiran into a Phase 3 TRITON program: TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, an open-label study using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), a large event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously once every six months. Nucresiran is investigational and not approved by the FDA, EMA or any regulator; it is studied only in clinical trials and is not a supplement or research chemical.", "url": "https://peptrackerpro.com/peptides/nucresiran", "lastReviewed": "2026-09-05", "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": "Nucresiran", "item": "https://peptrackerpro.com/peptides/nucresiran" } ] }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "Patients and families affected by hereditary or wild-type ATTR amyloidosis following the next generation of TTR-lowering treatments and how they compare with vutrisiran (Amvuttra), patisiran and eplontersen (Wainua)?", "acceptedAnswer": { "@type": "Answer", "text": "Nucresiran is a research peptide studied in preclinical models. An investigational next-generation RNA interference (RNAi) therapeutic from Alnylam Pharmaceuticals designed to silence the transthyretin (TTR) gene and treat transthyretin amyloidosis (ATTR) - the same disease targeted by Alnylam's approved drugs patisiran and vutrisiran (Amvuttra) and by Ionis/AstraZeneca's eplontersen (Wainua/Wainzua). Nucresiran (formerly ALN-TTRsc04) is a subcutaneous GalNAc-conjugated small interfering RNA (siRNA) built on Alnylam's newer IKARIA platform, engineered for deeper, more durable knockdown of both mutant and wild-type TTR with the potential for once- or twice-yearly dosing - a substantial step beyond the current quarterly (vutrisiran) or monthly (eplontersen) schedules. In an interim Phase 1 single-ascending-dose study in 48 healthy volunteers (presented at AHA 2024), a single dose of 300 mg or higher rapidly lowered serum TTR by more than 90% by Day 15 and by more than 96% at peak (Day 29), with more than 70% reduction still present at one year after a single 300 mg dose and low patient-to-patient variability; all doses were well tolerated with no injection-site reactions and no liver safety signals. Alnylam has moved nucresiran into a Phase 3 TRITON program: TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, an open-label study using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), a large event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously once every six months. Nucresiran is investigational and not approved by the FDA, EMA or any regulator; it is studied only in clinical trials and is not a supplement or research chemical." } }, { "@type": "Question", "name": "Cardiologists and neurologists tracking ATTR cardiomyopathy and polyneuropathy therapies and the prospect of once- or twice-yearly RNAi dosing?", "acceptedAnswer": { "@type": "Answer", "text": "Nucresiran is a research peptide studied in preclinical models. An investigational next-generation RNA interference (RNAi) therapeutic from Alnylam Pharmaceuticals designed to silence the transthyretin (TTR) gene and treat transthyretin amyloidosis (ATTR) - the same disease targeted by Alnylam's approved drugs patisiran and vutrisiran (Amvuttra) and by Ionis/AstraZeneca's eplontersen (Wainua/Wainzua). Nucresiran (formerly ALN-TTRsc04) is a subcutaneous GalNAc-conjugated small interfering RNA (siRNA) built on Alnylam's newer IKARIA platform, engineered for deeper, more durable knockdown of both mutant and wild-type TTR with the potential for once- or twice-yearly dosing - a substantial step beyond the current quarterly (vutrisiran) or monthly (eplontersen) schedules. In an interim Phase 1 single-ascending-dose study in 48 healthy volunteers (presented at AHA 2024), a single dose of 300 mg or higher rapidly lowered serum TTR by more than 90% by Day 15 and by more than 96% at peak (Day 29), with more than 70% reduction still present at one year after a single 300 mg dose and low patient-to-patient variability; all doses were well tolerated with no injection-site reactions and no liver safety signals. Alnylam has moved nucresiran into a Phase 3 TRITON program: TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, an open-label study using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), a large event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously once every six months. Nucresiran is investigational and not approved by the FDA, EMA or any regulator; it is studied only in clinical trials and is not a supplement or research chemical." } }, { "@type": "Question", "name": "Readers interested in RNA interference (RNAi) and Alnylam's newer IKARIA platform for deeper, longer-lasting gene silencing?", "acceptedAnswer": { "@type": "Answer", "text": "Nucresiran is a research peptide studied in preclinical models. An investigational next-generation RNA interference (RNAi) therapeutic from Alnylam Pharmaceuticals designed to silence the transthyretin (TTR) gene and treat transthyretin amyloidosis (ATTR) - the same disease targeted by Alnylam's approved drugs patisiran and vutrisiran (Amvuttra) and by Ionis/AstraZeneca's eplontersen (Wainua/Wainzua). Nucresiran (formerly ALN-TTRsc04) is a subcutaneous GalNAc-conjugated small interfering RNA (siRNA) built on Alnylam's newer IKARIA platform, engineered for deeper, more durable knockdown of both mutant and wild-type TTR with the potential for once- or twice-yearly dosing - a substantial step beyond the current quarterly (vutrisiran) or monthly (eplontersen) schedules. In an interim Phase 1 single-ascending-dose study in 48 healthy volunteers (presented at AHA 2024), a single dose of 300 mg or higher rapidly lowered serum TTR by more than 90% by Day 15 and by more than 96% at peak (Day 29), with more than 70% reduction still present at one year after a single 300 mg dose and low patient-to-patient variability; all doses were well tolerated with no injection-site reactions and no liver safety signals. Alnylam has moved nucresiran into a Phase 3 TRITON program: TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, an open-label study using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), a large event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously once every six months. Nucresiran is investigational and not approved by the FDA, EMA or any regulator; it is studied only in clinical trials and is not a supplement or research chemical." } }, { "@type": "Question", "name": "Investors and industry watchers monitoring Alnylam's effort to extend its TTR franchise against stabilizers (tafamidis, acoramidis) and gene editing (NTLA-2001 / nexiguran ziclumeran)?", "acceptedAnswer": { "@type": "Answer", "text": "Nucresiran is a research peptide studied in preclinical models. An investigational next-generation RNA interference (RNAi) therapeutic from Alnylam Pharmaceuticals designed to silence the transthyretin (TTR) gene and treat transthyretin amyloidosis (ATTR) - the same disease targeted by Alnylam's approved drugs patisiran and vutrisiran (Amvuttra) and by Ionis/AstraZeneca's eplontersen (Wainua/Wainzua). Nucresiran (formerly ALN-TTRsc04) is a subcutaneous GalNAc-conjugated small interfering RNA (siRNA) built on Alnylam's newer IKARIA platform, engineered for deeper, more durable knockdown of both mutant and wild-type TTR with the potential for once- or twice-yearly dosing - a substantial step beyond the current quarterly (vutrisiran) or monthly (eplontersen) schedules. In an interim Phase 1 single-ascending-dose study in 48 healthy volunteers (presented at AHA 2024), a single dose of 300 mg or higher rapidly lowered serum TTR by more than 90% by Day 15 and by more than 96% at peak (Day 29), with more than 70% reduction still present at one year after a single 300 mg dose and low patient-to-patient variability; all doses were well tolerated with no injection-site reactions and no liver safety signals. Alnylam has moved nucresiran into a Phase 3 TRITON program: TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, an open-label study using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), a large event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously once every six months. Nucresiran is investigational and not approved by the FDA, EMA or any regulator; it is studied only in clinical trials and is not a supplement or research chemical." } }, { "@type": "Question", "name": "People comparing siRNA and antisense (ASO) approaches to TTR amyloidosis and how nucresiran fits alongside other GalNAc-conjugated RNAi medicines?", "acceptedAnswer": { "@type": "Answer", "text": "Nucresiran is a research peptide studied in preclinical models. An investigational next-generation RNA interference (RNAi) therapeutic from Alnylam Pharmaceuticals designed to silence the transthyretin (TTR) gene and treat transthyretin amyloidosis (ATTR) - the same disease targeted by Alnylam's approved drugs patisiran and vutrisiran (Amvuttra) and by Ionis/AstraZeneca's eplontersen (Wainua/Wainzua). Nucresiran (formerly ALN-TTRsc04) is a subcutaneous GalNAc-conjugated small interfering RNA (siRNA) built on Alnylam's newer IKARIA platform, engineered for deeper, more durable knockdown of both mutant and wild-type TTR with the potential for once- or twice-yearly dosing - a substantial step beyond the current quarterly (vutrisiran) or monthly (eplontersen) schedules. In an interim Phase 1 single-ascending-dose study in 48 healthy volunteers (presented at AHA 2024), a single dose of 300 mg or higher rapidly lowered serum TTR by more than 90% by Day 15 and by more than 96% at peak (Day 29), with more than 70% reduction still present at one year after a single 300 mg dose and low patient-to-patient variability; all doses were well tolerated with no injection-site reactions and no liver safety signals. Alnylam has moved nucresiran into a Phase 3 TRITON program: TRITON-PN (NCT07223203) in hereditary ATTR with polyneuropathy, an open-label study using vutrisiran as an active comparator, and TRITON-CM (NCT07052903), a large event-driven cardiovascular outcomes trial in ATTR cardiomyopathy dosing nucresiran 300 mg subcutaneously once every six months. Nucresiran is investigational and not approved by the FDA, EMA or any regulator; it is studied only in clinical trials and is not a supplement or research chemical." } } ] } ] ```