Pelacarsen

Pelacarsen is not approved for any use anywhere. It is being evaluated in the pivotal Phase 3 Lp(a)HORIZON cardiovascular outcomes trial (NCT04023552; 8,323 patients with established CVD and Lp(a) ≥ 70 mg/dL), the first-ever outcomes trial for an Lp(a)-lowering therapy. Topline data were originally expected in 2025, then guided to a mid-2026 window; the readout is imminent as of mid-2026, with Novartis planning regulatory submissions thereafter. Licensed by Novartis from Ionis for exclusive worldwide development, manufacturing, and commercialization.

Effective: 2026

An oral PCSK9 inhibitor peptide that reduced LDL cholesterol by 57% in Phase 3 trials — matching injectable monoclonal antibodies in efficacy while offering once-daily pill convenience.

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.

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)).

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.

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.

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.

Sotatercept (Winrevair, sotatercept-csrk) is Merck's first-in-class activin signaling inhibitor - a recombinant ActRIIA-Fc fusion protein that acts as a ligand trap for activin A, activin B, GDF-8 (myostatin) and GDF-11. It is FDA-approved for adults with pulmonary arterial hypertension (PAH), where it improved 6-minute walk distance by 40.8 meters in the Phase 3 STELLAR trial and, in the Phase 3 ZENITH trial in high-risk patients, cut the composite risk of death, lung transplantation and PAH hospitalization by 76%. An expanded U.S. label reflecting ZENITH was approved on October 27, 2025.

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).

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.

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, 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.

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-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.