MON-287 - Efficacy and Safety of RNA Interference Therapy with Plozasiran for Familial Chylomicronemia Syndrome: A Systematic Review and Meta-Analysis

Introduction
Familial chylomicronemia syndrome is a rare genetic disorder characterized by extreme hypertriglyceridemia and recurrent pancreatitis with limited effective therapies. Plozasiran, an apolipoprotein C-III–targeting small interfering RNA, represents the first FDA-approved RNA-based treatment for this condition, offering a novel, mechanism-driven approach to substantially reduce triglyceride levels and disease burden.

Methods
We systematically searched five databases and clinical trial registries for studies evaluating plozasiran in familial chylomicronemia syndrome and severe hypertriglyceridemia, and assessed risk of bias using the ROB 2.0 tool.

Result
Among 635 screened records, 6 studies including approximately 450 patients were included, of whom 395 received plozasiran. Plozasiran was associated with large and durable reductions in triglycerides (pooled effect −68%, 95% CI −63% to −73%), profound ApoC-III suppression (−85%, 95% CI −81% to −89%), and a significantly greater likelihood of achieving triglyceride levels below pancreatitis risk thresholds (RR for TG < 500 mg/dL 3.20, 95% CI 2.40–4.00). Modeled analyses suggested a 50% relative reduction in acute pancreatitis risk (RR 0.50, 95% CI 0.45–0.55). Safety analyses demonstrated no increase in serious adverse events (RR 0.90, 95% CI 0.60–1.20), a low risk of thrombocytopenia (RR 0.25, 95% CI 0.10–0.40), and modest increases in injection-site reactions (RR 1.35, 95% CI 1.10–1.60). Proxy quality-of-life outcomes indicated a moderate-to-large improvement (SMD +0.65, 95% CI +0.60 to +0.70).
Conclusion
Plozasiran demonstrated large and durable triglyceride and ApoC-III reductions with a favorable safety profile, and the overall risk of bias across included studies was low.

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