Lipid-efficacy RCT · N Engl J Med 2025
PALISADE trial
Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk.
The bottom line
In patients with persistent chylomicronemia, plozasiran (siRNA against APOC3) sharply lowered triglycerides and reduced acute pancreatitis episodes compared with placebo, with a similar overall adverse event rate but a signal for hyperglycemia in those with prediabetes/diabetes.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Subcutaneous plozasiran (25 mg or 50 mg) every 3 months
- Compared with
- Placebo (subcutaneous, every 3 months for 12 months)
- People
- 75
- Who took part
- Patients with persistent chylomicronemia (with or without a genetic diagnosis), classically caused by familial chylomicronemia syndrome (FCS); baseline median triglyceride level 2044 mg per deciliter
- Design
- Randomized, placebo-controlled, phase 3 trial (dose groups: 25 mg, 50 mg, and placebo)
- Follow-up
- 12 months
- Main question
- Median percent change from baseline in the fasting triglyceride level at 10 months
Main result
Median change from baseline in fasting triglyceride level at 10 months was -80% in the 25-mg plozasiran group, -78% in the 50-mg plozasiran group, and -17% in the placebo group (P<0.001)
Effect on LDL cholesterol
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Other results
Incidence of acute pancreatitis: odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P = 0.03. Also key secondary end points included percent change in fasting triglyceride level from baseline to mean of values at 10 and 12 months, and changes in fasting apolipoprotein C-III level from baseline to 10 and 12 months, all better with plozasiran than placebo.
Safety
The risk of adverse events was similar across groups; the most common adverse events were abdominal pain, nasopharyngitis, headache, and nausea. Severe and serious adverse events were less common with plozasiran than with placebo. Hyperglycemia with plozasiran occurred in some patients with prediabetes or diabetes at baseline.
In the trial's own words
“At 10 months, the median change from baseline in the fasting triglyceride level (the primary end point) was -80% in the 25-mg plozasiran group, -78% in the 50-mg plozasiran group, and -17% in the placebo group (P<0.001). The key secondary end points showed better results in the plozasiran groups than in the placebo group, including the incidence of acute pancreatitis (odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P = 0.03).”
Quoted from the abstract of N Engl J Med 2025, checked word for word against PubMed. PubMed 39225259 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Plozasiran (Redemplo)
Common questions
What did the PALISADE trial find?
In patients with persistent chylomicronemia, plozasiran (siRNA against APOC3) sharply lowered triglycerides and reduced acute pancreatitis episodes compared with placebo, with a similar overall adverse event rate but a signal for hyperglycemia in those with prediabetes/diabetes.
Who was in PALISADE?
75 people. Patients with persistent chylomicronemia (with or without a genetic diagnosis), classically caused by familial chylomicronemia syndrome (FCS); baseline median triglyceride level 2044 mg per deciliter.
What was PALISADE's main result?
Median change from baseline in fasting triglyceride level at 10 months was -80% in the 25-mg plozasiran group, -78% in the 50-mg plozasiran group, and -17% in the placebo group (P<0.001)
How much did LDL cholesterol change in PALISADE?
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Related trials
- CTX310 phase 1 (2025)A single dose of the CRISPR-Cas9 gene-editing therapy CTX310 was generally well tolerated and produced dose-dependent reductions in ANGPTL3 levels, supporting further clinical development for dyslipidemia.
- ESSENCE-TIMI 73b (2025)In patients with moderate hypertriglyceridemia and elevated cardiovascular risk, olezarsen significantly lowered triglyceride levels at 6 months compared with placebo, with similar rates of serious adverse events.
- PROLONG-ANG3 (2025)In adults with mixed dyslipidaemia on background statin therapy, solbinsiran 400 mg significantly reduced apoB levels compared with placebo and was generally well tolerated, though its effect on cardiovascular outcomes is still unknown.
- ARCHES-2 (2024)In adults with mixed hyperlipidemia, zodasiran (an RNAi therapy against ANGPTL3) produced significant, dose-dependent reductions in triglycerides and improvements in non-HDL-C, ApoB, and LDL-C compared with placebo, with a signal of transient HbA1c elevation in diabetic patients at the highest dose.
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