Olpasiran, lepodisiran and zerlasiran: how it works, status and trials
Olpasiran, lepodisiran phase 3 outcome trials; zerlasiran phase 2siRNA injectionLowering lipoprotein(a)
Olpasiran, lepodisiran and zerlasiran are investigational injections that cut the messenger RNA for apo(a), so the liver makes less lipoprotein(a). Olpasiran and lepodisiran are in phase 3 outcome trials, zerlasiran is in phase 2, and none is approved.
In technical terms: RISC-mediated cleavage of LPA mRNA.
The highlighted badge marks where Olpasiran, lepodisiran and zerlasiran acts. Open the full map or compare every therapy.
At a glance
- Acts on
- LPA mRNA · liver
- How it is given
- GalNAc-siRNA · SC every 12 weeks to 6 months
- What the main trial found
- Lp(a) −97% (olpasiran), −94% (lepodisiran), −81% to −86% (zerlasiran), placebo-adjusted
- Status (curated October 25, 2026)
- Olpasiran, lepodisiran phase 3 outcome trials; zerlasiran phase 2
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.
Olpasiran from Amgen
Stage: Phase 3. 3 active of 9 registered trials. 4 new papers in the last 31 days.
- NCT05581303 (NCT05581303): active not recruiting, primary completion 2028-03-31
Lepodisiran from Eli Lilly
Stage: Phase 3. 2 active of 7 registered trials. 4 new papers in the last 31 days.
- NCT06292013 (NCT06292013): active not recruiting, primary completion 2029-03
Zerlasiran from Silence Therapeutics
Stage: Phase 2. 0 active of 2 registered trials. 4 new papers in the last 31 days.
- NCT05537571 (NCT05537571): completed, primary completion 2024-01-11, results posted
Evidence
- OCEAN(a)-DOSE (PubMed 36342163)
- Lepodisiran ph2 (PubMed 40162643)
- Zerlasiran ph2 (PubMed 39556769)
Common questions
How does Olpasiran, lepodisiran and zerlasiran work?
Olpasiran, lepodisiran and zerlasiran are investigational injections that cut the messenger RNA for apo(a), so the liver makes less lipoprotein(a). Olpasiran and lepodisiran are in phase 3 outcome trials, zerlasiran is in phase 2, and none is approved. In technical terms: RISC-mediated cleavage of LPA mRNA. It acts on LPA mRNA · liver.
How much does Olpasiran, lepodisiran and zerlasiran lower cholesterol or other lipids?
Lp(a) −97% (olpasiran), −94% (lepodisiran), −81% to −86% (zerlasiran), placebo-adjusted. Individual results differ, and a clinician can say what to expect for one person.
Is Olpasiran, lepodisiran and zerlasiran approved, and what is the status?
Olpasiran, lepodisiran phase 3 outcome trials; zerlasiran phase 2 (curated October 25, 2026). Registry stage as of October 27, 2026: Olpasiran, Phase 3; Lepodisiran, Phase 3; Zerlasiran, Phase 2.
How is Olpasiran, lepodisiran and zerlasiran taken?
GalNAc-siRNA · SC every 12 weeks to 6 months.
Read more
Related therapies
- Pelacarsen: Phase 3 (outcome trial negative)
- 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.