Olezarsen (Tryngolza) and volanesorsen: how it works, status and trials
Olezarsen approved 2024; volanesorsen EU onlyAntisense injectionLowering triglycerides
Olezarsen (Tryngolza) and volanesorsen are injections that break down the messenger RNA for apoC-III, a protein that slows triglyceride clearance. With less apoC-III, the body clears triglyceride-rich particles faster. Olezarsen was approved in 2024, and volanesorsen is available in the EU only.
In technical terms: RNase H1 degrades APOC3 mRNA; less apoC-III lets LPL clear TG-rich particles faster.
The highlighted badge marks where Olezarsen (Tryngolza) and volanesorsen acts. Open the full map or compare every therapy.
At a glance
- Acts on
- APOC3 mRNA · liver
- How it is given
- Antisense oligonucleotide · SC monthly (olezarsen) / weekly
- What the main trial found
- Olezarsen TG −49 to −58 pp (moderate HTG); volanesorsen TG −77% (FCS)
- Status (curated October 25, 2026)
- Olezarsen approved 2024; volanesorsen EU only
Where it fits in the body
Triglyceride-rich lipoproteins
VLDL from the liver and chylomicrons from the gut carry triglyceride. Lipoprotein lipase (LPL) on capillary walls breaks it down. ANGPTL3 and apoC-III act as brakes on this process. Removing either brake (11–15) lowers triglycerides, and ANGPTL3 blockade also lowers LDL-C without needing LDL receptors, which matters in homozygous FH.
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.
Olezarsen (Tryngolza) from Ionis
Stage: US approved 2024-12-19. 4 active of 11 registered trials. 8 new papers in the last 31 days.
- NCT05610280 (NCT05610280): completed, primary completion 2024-08-08
Recent changes
- October 25, 2026: PMID 42886196: Olezarsen Reduces Triglyceride Levels and the Risk of Acute Pancreatitis in People With Severe Hypertriglyceridemia.
- October 25, 2026: PMID 42866822: Silencing apolipoprotein C-III to silence pancreatitis: olezarsen and the maturation of RNA-targeted therapy for severe hypertriglyceridemia
- October 25, 2026: PMID 42837875: Olezarsen for the treatment of hypertriglyceridemia: A Bayesian reanalysis of randomized controlled trials.
- October 25, 2026: PMID 42814299: Olezarsen for the Treatment of Hypertriglyceridemia.
Evidence
- Olezarsen, moderate HTG (PubMed 40888739)
- Volanesorsen APPROACH (PubMed 31390500)
Common questions
How does Olezarsen (Tryngolza) and volanesorsen work?
Olezarsen (Tryngolza) and volanesorsen are injections that break down the messenger RNA for apoC-III, a protein that slows triglyceride clearance. With less apoC-III, the body clears triglyceride-rich particles faster. Olezarsen was approved in 2024, and volanesorsen is available in the EU only. In technical terms: RNase H1 degrades APOC3 mRNA; less apoC-III lets LPL clear TG-rich particles faster. It acts on APOC3 mRNA · liver.
How much does Olezarsen (Tryngolza) and volanesorsen lower cholesterol or other lipids?
Olezarsen TG −49 to −58 pp (moderate HTG); volanesorsen TG −77% (FCS). Individual results differ, and a clinician can say what to expect for one person.
Is Olezarsen (Tryngolza) and volanesorsen approved, and what is the status?
Olezarsen approved 2024; volanesorsen EU only (curated October 25, 2026). Registry stage as of October 27, 2026: Olezarsen, US approved 2024-12-19.
How is Olezarsen (Tryngolza) and volanesorsen taken?
Antisense oligonucleotide · SC monthly (olezarsen) / weekly.
Read more
Related therapies
- Evinacumab (Evkeeza): Approved 2021 (HoFH)
- Plozasiran (Redemplo): Approved Nov 2025 (FCS)
- Fibrates (fenofibrate): Approved (generic)
- Icosapent ethyl (Vascepa): Approved
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.