Pelacarsen: how it works, status and trials
Phase 3 (outcome trial negative)Antisense injectionLowering lipoprotein(a)
Pelacarsen is an investigational monthly injection that breaks down the messenger RNA for apo(a), so the liver makes less lipoprotein(a). Its large outcome trial missed its main goal, and it is not approved.
In technical terms: RNase H1 degrades LPA mRNA, so less apo(a) is made.
The highlighted badge marks where Pelacarsen acts. Open the full map or compare every therapy.
At a glance
- Acts on
- LPA mRNA (apo(a)) · liver
- How it is given
- GalNAc-antisense · SC monthly
- What the main trial found
- Lp(a) −35% to −80% (phase 2); missed primary endpoint in Lp(a)HORIZON
- Status (curated October 25, 2026)
- Phase 3 (outcome trial negative)
Where it fits in the body
Lipoprotein(a)
Lp(a) is an LDL-like particle with an extra protein, apo(a), made from the LPA gene. Its level is about 90% genetically determined. Antisense and siRNA drugs (16, 17) stop apo(a) production; muvalaplin (18) blocks apo(a) from attaching to apoB. Pelacarsen did not meet its primary outcome; other outcome trials are ongoing.
RNA and gene-editing therapies
These drugs act before a protein is made. siRNA and antisense drugs are attached to GalNAc, which hepatocytes take up, and they destroy one specific mRNA. A dose lasts weeks to months. Gene editors (10, 13) make a permanent single-dose change to the DNA and are in early trials.
Trials and registry status
From ClinicalTrials.gov, PubMed and openFDA, refreshed monthly. Last run October 27, 2026.
Pelacarsen from Novartis / Ionis
Stage: Phase 3. 5 active of 13 registered trials. 5 new papers in the last 31 days.
- Lp(a)HORIZON (NCT04023552): completed, primary completion 2026-07-16
Recent changes
- October 25, 2026: PMID 42886494: Lp(a)-Reducing Agent Pelacarsen Misses the Mark in Phase 3-Now What?
- October 25, 2026: PMID 42880684: Pelacarsen and Lp(a)HORIZON: Interpreting the Disconnect Between Lipoprotein(a) Lowering and Cardiovascular Outcomes.
Evidence
- Phase 2, NEJM 2020 (PubMed 31893580)
- Lp(a)HORIZON commentary (PubMed 42886494)
Common questions
How does Pelacarsen work?
Pelacarsen is an investigational monthly injection that breaks down the messenger RNA for apo(a), so the liver makes less lipoprotein(a). Its large outcome trial missed its main goal, and it is not approved. In technical terms: RNase H1 degrades LPA mRNA, so less apo(a) is made. It acts on LPA mRNA (apo(a)) · liver.
How much does Pelacarsen lower cholesterol or other lipids?
Lp(a) −35% to −80% (phase 2); missed primary endpoint in Lp(a)HORIZON. Individual results differ, and a clinician can say what to expect for one person.
Is Pelacarsen approved, and what is the status?
Phase 3 (outcome trial negative) (curated October 25, 2026). Registry stage as of October 27, 2026: Pelacarsen, Phase 3.
How is Pelacarsen taken?
GalNAc-antisense · SC monthly.
Read more
Related therapies
- Olpasiran, lepodisiran and zerlasiran: Olpasiran, lepodisiran phase 3 outcome trials; zerlasiran phase 2
- Muvalaplin: Phase 3
Educational, not medical advice. Mechanism and status text curated October 25, 2026; registry data refreshed October 27, 2026. Registries can lag company announcements. Effects are placebo-adjusted results from the main published trial, not head-to-head comparisons. Investigational agents are available only in clinical trials. Preval Health does not practice medicine; licensed clinicians in a partner network provide care. If you have chest pain or signs of a stroke, call 911.