Redemplo (plozasiran) is an RNA interference (siRNA) therapy that silences the APOC3 gene in the liver, dramatically reducing triglyceride levels. FDA-approved in December 2024 for adults with severe hypertriglyceridemia (โฅ500 mg/dL), it is given as a once-quarterly subcutaneous injection.
Redemplo (plozasiran) was FDA-approved in December 2024, manufactured by Arrowhead Pharmaceuticals. It is a small interfering RNA (siRNA) โ a type of gene-silencing molecule that prevents liver cells from making the APOC3 protein, which normally inhibits triglyceride clearance. By suppressing APOC3, plozasiran dramatically lowers triglyceride levels and reduces the risk of acute pancreatitis.
How Does Redemplo Work?
APOC3 (apolipoprotein C-III) is a protein produced in the liver that:
- Inhibits lipoprotein lipase (LPL), the enzyme that breaks down triglycerides in the blood
- Slows the clearance of triglyceride-rich lipoproteins (VLDL, chylomicrons)
- When overproduced or not cleared quickly, APOC3 leads to very high triglyceride levels
Plozasiran is an siRNA molecule delivered to liver cells via a GalNAc conjugate. Once inside the cell, it triggers RNA interference โ a natural cellular process that degrades the APOC3 messenger RNA before it can be translated into protein. Less APOC3 โ more active LPL โ faster triglyceride clearance from the blood.
Who Is Redemplo For?
Redemplo is FDA-approved for adults with severe hypertriglyceridemia (triglycerides โฅ 500 mg/dL). This level dramatically increases the risk of acute pancreatitis โ a serious, potentially life-threatening inflammation of the pancreas.
It may be appropriate for patients who:
- Have genetic conditions affecting triglyceride metabolism (e.g., familial hypertriglyceridemia, partial LPL deficiency)
- Have not achieved adequate triglyceride control with diet, fibrates, or omega-3 fatty acids
- Have had prior episodes of hypertriglyceridemia-induced pancreatitis
โ ๏ธ Why it matters: Triglycerides above 500 mg/dL carry a significant risk of acute pancreatitis, which can be severe and recurrent. At levels above 1,000โ2,000 mg/dL (as seen in familial chylomicronemia), pancreatitis risk is very high. Controlling triglycerides in these patients is a medical priority.
PALISADE Trial โ The Evidence
The pivotal PALISADE trial evaluated plozasiran in patients with severe hypertriglyceridemia (median triglycerides ~1,200 mg/dL at baseline). Key results at 12 months:
| Outcome | Result |
|---|---|
| Triglyceride reduction | ~70โ80% from baseline |
| Patients reaching triglycerides <500 mg/dL | ~80% of treated patients |
| APOC3 reduction | ~80โ90% |
| Pancreatitis episodes | Significantly reduced vs. placebo |
Dosing and Administration
- Dose: 25 mg subcutaneous injection
- Frequency: Once every 3 months (quarterly)
- Injected into the abdomen, thigh, or upper arm
- Administered by a healthcare provider or self-administered after training
- Triglycerides begin to fall within 1โ2 weeks; nadir at approximately 2โ3 months
Side Effects
Plozasiran is generally well tolerated. Most common side effects in clinical trials:
- Injection site reactions (mild, transient)
- Arthralgia (joint pain)
- Nausea
- Fatigue
Unlike fibrates, plozasiran does not interact with statins and does not carry a risk of myopathy. Because it targets only APOC3 mRNA in hepatocytes, its effects are hepatocyte-specific.
Redemplo vs. Other Triglyceride-Lowering Therapies
| Therapy | Mechanism | TG Reduction | Administration |
|---|---|---|---|
| Redemplo (plozasiran) | siRNA โ silences APOC3 | ~70โ80% | Quarterly injection |
| Tryngolza (olezarsen) | ASO โ silences APOC3 | ~60โ70% | Monthly injection |
| Fibrates (fenofibrate) | PPAR-ฮฑ agonist | ~30โ50% | Daily oral |
| Omega-3 FA (Vascepa, Lovaza) | Multiple TG pathways | ~20โ30% | Daily oral |
Key Takeaways
- Redemplo (plozasiran) is a quarterly siRNA injection that silences APOC3 โ a key regulator of triglyceride clearance
- Reduces triglycerides by ~70โ80%; FDA-approved December 2024 for severe hypertriglyceridemia โฅ500 mg/dL
- Significantly reduces acute pancreatitis risk in patients with very high triglycerides
- Once-quarterly dosing improves adherence compared to daily medications
- Well tolerated; no known statin interaction or myopathy risk
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