Vutrisiran

FDA-approved as Amvuttra for the polyneuropathy of hereditary ATTR amyloidosis (June 13, 2022) and, following a March 20, 2025 label expansion, for the cardiomyopathy of wild-type or hereditary ATTR amyloidosis in adults to reduce cardiovascular death, cardiovascular hospitalizations and urgent heart-failure visits; also approved in the European Union and other markets, with the EU cardiomyopathy indication granted in 2025. It is a healthcare-professional-administered subcutaneous injection dispensed by prescription - not a dietary supplement or research chemical.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.