| What it is |
Eplontersen is an antisense oligonucleotide (ASO) that targets the mRNA of apolipoprotein C‑III (apoC‑III). By reducing apoC‑III levels, it lowers plasma triglycerides and has potential benefits for atherosclerotic disease. |
| Manufacturer |
Epizyme, Inc. (the drug is also referred to as “Eplontersen” or “Eplontersen‑ALN‑AC003”). |
| Current status |
Investigational – Phase III trials (ELOQUENT‑1 & -2) are assessing its efficacy in patients with severe hypertriglyceridemia and cardiovascular risk. No regulatory approval in the U.S. or EU yet. |
| Intended use |
Primary treatment for severe hypertriglyceridemia (fasting triglycerides ≥ 500 mg/dL, often > 1000 mg/dL) and for reducing cardiovascular events in high‑risk patients. |
| How it works |
• Binds to apoC‑III mRNA → promotes its degradation via RNase H.
• ↓ ApoC‑III → ↓ VLDL production, ↑ lipoprotein lipase activity, ↓ plasma triglycerides.
• ApoC‑III also inhibits LDL receptor recycling, so lowering it may also modestly improve LDL‑C. |
| Dosing (in trials) |
Subcutaneous injection 200 mg every 2 weeks (some regimens use 200 mg weekly; dosing varies by study). |
| Administration |
Subcutaneous injection (self‑administered at home in most trials). |
| Common side effects |
• Injection‑site reactions (pain, redness, swelling).
• Flu‑like symptoms (fever, malaise).
• Mild headaches.
Rarely, elevated liver enzymes or mild neutropenia reported in early studies. |
| Serious risks |
• Serious infections (rare).
• Hypersensitivity/anaphylaxis (rare).
• Potential for off‑target RNA effects, but no major safety signals so far. |
| Contraindications |
• Known hypersensitivity to eplontersen or its excipients.
• Severe, uncontrolled infections (if injection‑site infection risk is high). |
| Drug interactions |
No known CYP‑450 interactions (ASOs are not metabolized by those enzymes).
• Avoid concurrent use with other investigational RNA‑based therapies that may compete for similar pathways. |
| Special populations |
• Limited data in pregnancy, lactation, or severe renal/hepatic impairment.
• Use with caution in the elderly; monitor for injection‑site reactions. |
| Monitoring |
• Baseline & periodic lipid panels (triglycerides, LDL‑C, HDL‑C).
• Liver function tests (ALT/AST).
• CBC if clinically indicated. |
| Clinical evidence |
Phase II (ELOQUENT‑1) showed a ~60–70 % reduction in triglycerides after 12 weeks. Phase III (ELOQUENT‑2) is ongoing to confirm safety and cardiovascular benefit. |
| Availability |
Not yet commercially available. Patients can only access eplontersen via clinical trials. |