Pelacarsen
Medium EvidenceA 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.
What It Is
Pelacarsen is a first-in-class, once-monthly subcutaneous antisense oligonucleotide (ASO) being developed by Ionis Pharmaceuticals and Novartis to lower lipoprotein(a) — commonly written Lp(a) — a genetically determined, causal risk factor for heart attack, stroke, peripheral artery disease, and calcific aortic valve stenosis. Roughly one in five people worldwide inherit high Lp(a), and unlike LDL cholesterol it cannot be meaningfully changed by diet, exercise, statins, or PCSK9 inhibitors; there is currently no approved therapy that specifically and robustly lowers it. Pelacarsen attacks the problem at its source: it is a GalNAc-conjugated (LICA, Ligand-Conjugated Antisense) oligonucleotide that is taken up by liver cells and binds the messenger RNA for apolipoprotein(a) — the LPA gene product that defines the Lp(a) particle — triggering its degradation so the liver makes far less apo(a) and assembles far fewer Lp(a) particles. In Phase 2, the 80 mg monthly dose reduced Lp(a) by roughly 80% and brought 98% of participants below the guideline risk threshold of 50 mg/dL. The compound (formerly IONIS-APO(a)-LRx / TQJ230) was discovered by Ionis using its LICA platform and licensed to Novartis for worldwide development in 2019. The pivotal Phase 3 Lp(a)HORIZON trial (NCT04023552) enrolled 8,323 patients with established cardiovascular disease and Lp(a) ≥ 70 mg/dL into a global, double-blind, placebo-controlled study, testing whether lowering Lp(a) with 80 mg pelacarsen monthly reduces major adverse cardiovascular events (expanded MACE: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and urgent coronary revascularization). Crucially, Lp(a)HORIZON is the first cardiovascular outcomes trial for any Lp(a)-targeting therapy, so its readout will not only decide pelacarsen's fate but also test the central hypothesis that lowering Lp(a) prevents cardiovascular events — validating or challenging an entire emerging drug class that includes the siRNAs olpasiran, lepodisiran, and zerlasiran. Topline results were originally guided for 2025 and then to a mid-2026 window, with the readout imminent as of mid-2026 and Novartis planning regulatory submissions to follow. Pelacarsen is investigational and not approved anywhere; it is a clinical-stage prescription medicine, not a supplement or research chemical.
Regulatory Status
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
View FDA SourceWhy Researchers Study It
Pelacarsen is the compound that will answer the field's biggest open question in cardiovascular medicine: does lowering lipoprotein(a) actually prevent heart attacks and strokes? Lp(a) has been recognized for decades as an independent, inherited, causal risk factor for cardiovascular disease, but no therapy has ever been able to lower it specifically — and no outcomes trial has ever tested whether doing so helps. Pelacarsen's Lp(a)HORIZON trial is the first such experiment. Researchers study it both as a potentially first-in-class treatment for the ~20% of people born with high Lp(a) and as a proof-of-concept for the entire Lp(a)-lowering class (which also includes the siRNAs olpasiran, lepodisiran, and zerlasiran). A positive readout would establish Lp(a) as a modifiable target and open a new front in preventive cardiology; a null result would reshape how the field thinks about the risk factor.
Proposed Mechanisms
- GalNAc-conjugated (LICA) antisense oligonucleotide taken up selectively by hepatocytes
- Binds and triggers degradation of apolipoprotein(a) [LPA] messenger RNA in the liver, reducing apo(a) synthesis
- Fewer apo(a) molecules means the liver assembles far fewer Lp(a) particles, lowering circulating Lp(a) by ~80%
- Aims to reduce the atherogenic, pro-inflammatory, and thrombogenic cardiovascular risk carried by Lp(a) independent of LDL cholesterol
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Phase 2 (dose-ranging, elevated Lp(a) with CVD) | Adults with established cardiovascular disease and elevated Lp(a) | Monthly pelacarsen produced dose-dependent Lp(a) lowering of up to ~80%; the 80 mg monthly dose selected for Phase 3 reduced Lp(a) below the guideline risk threshold (<50 mg/dL) in 98% of participants | Source |
| Phase 3 (Lp(a)HORIZON, cardiovascular outcomes, NCT04023552) | 8,323 adults with established CVD and Lp(a) ≥ 70 mg/dL — global, randomized, double-blind, placebo-controlled | First-ever CV outcomes trial for an Lp(a)-lowering drug; primary endpoint is superiority vs placebo in reducing expanded MACE (CV death, non-fatal MI, non-fatal stroke, urgent coronary revascularization). Fully enrolled; topline readout expected 2026 | Source |
| Mechanism / target validation | Human genetics and epidemiology of lipoprotein(a) | Elevated Lp(a) is an independent, inherited, causal risk factor for coronary heart disease, stroke, peripheral artery disease, and aortic stenosis, affecting roughly 20% of people; it is not lowered by lifestyle, statins, or PCSK9 inhibitors — establishing the rationale for a specific apo(a)-lowering therapy | Source |
Commonly Discussed Benefits
Researching Pelacarsen? Track it, set reminders, and keep notes in the free app.
Safety & Cautions
- Investigational — not approved for any use anywhere; efficacy on cardiovascular events has not yet been demonstrated (Lp(a)HORIZON topline pending in 2026)
- Robust Lp(a) lowering (~80%) is established, but whether that lowering translates into fewer heart attacks and strokes is exactly what the pending outcomes trial is designed to test
- A prescription clinical-stage biologic administered by subcutaneous injection under medical supervision — not a supplement, nootropic, or research chemical
- Any 'pelacarsen', 'TQJ230', or 'apo(a)-LRx' offered by a vendor is unverified and not a legitimate source of this investigational medicine
- Not interchangeable with LDL-lowering drugs (statins, PCSK9 inhibitors); it targets Lp(a), a distinct, genetically determined lipoprotein
Comparisons
See how Pelacarsen compares to related peptides:
Calculator Tools
Use our research tools to explore dosing and reconstitution data:
Citations
- [1] Ionis — Enrollment Completion of Phase 3 Lp(a)HORIZON Cardiovascular Outcomes Study of Pelacarsen (trial design, 80 mg monthly, 8,325 participants, Phase 2 data) PubMed
- [2] Lp(a)HORIZON — Assessing the Effect of Lipoprotein(a) Lowering With Pelacarsen on Major Cardiovascular Events (ClinicalTrials.gov NCT04023552) PubMed
- [3] Lipoprotein(a): An Independent Risk Factor for CV Disease — American College of Cardiology PubMed
- [4] Pelacarsen: Mechanism of Action and Lp(a)-Lowering Effect — Journal of Clinical Lipidology PubMed
- [5] 2026 Cardiovascular Catalysts: Lp(a) on the Horizon — BioCentury PubMed
Keep researching in the app
- Log Pelacarsen to your private tracker
- Set a dosing reminder
- Compare it side-by-side with your stack
Related Peptides
Enlicitide
High EvidenceAn 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.
Sotatercept
High EvidenceSotatercept (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.
WVE-007
Low EvidenceWVE-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.
Olpasiran
Medium EvidenceAn 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.
Lepodisiran
Medium EvidenceAn 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.
Zerlasiran
Medium EvidenceAn 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.