RX Review: Leveraging siRNA in FCS Management - Episode 4
RX Review: Understanding Plozasiran’s Role in FCS Management
Panelists break down the potential role of plozasiran in FCS based on the PALISADE trial.
The US Food and Drug Administration's November 2025 approval of plozasiran (Redemplo) marks a significant shift in the landscape of familial chylomicronemia syndrome (FCS), with the field now entering an era with multiple approved therapies following the 2024 approval of olezarsen (Tryngolza).
In part 4 of this 7-part video series, host Viet Le, DMSc, PA-C, a preventive cardiology PA at Intermountain Health and the former president of the Academy of Physician Associates in Cardiology, welcomes Christie Ballantyne, MD, chief of cardiovascular research at Baylor College of Medicine and principal investigator of the PALISADE trial, focus on plozasiran and its role in contemporary FCS management.
Ballantyne begins by reviewing the mechanism of action of small interfering RNA therapies and how they modulate pathways independent of lipoprotein lipase activity. This mechanism is particularly valuable for patients with FCS, who lack functional LPL-mediated triglyceride clearance. Ballantyne highlights clinical studies have shown substantial reductions in median triglyceride levels along with meaningful decreases in pancreatitis episodes, outcomes were historically unattainable with earlier therapies.
Plozasiran received FDA approval on November 18, 2025, making it the second disease-targeted therapy available for individuals with FCS, following the approval of olezarsen in late 2024. Ballantyne compares the therapeutic classes, noting distinctions between antisense oligonucleotides such as olezarsen and siRNA agents such as plozasiran. Differences in dosing frequency, safety profiles, and trial endpoints may influence clinician decision-making. Le and Ballantyne underscore even with potent new agents, ongoing lifestyle management remains important, particularly in preventing secondary complications.
The discussion closes by highlighting how plozasiran expands treatment options for a historically underserved population. Ballantyne remarks the approval signals a new era in FCS therapy and demonstrates the value of precision approaches to rare metabolic diseases. The segment emphasizes specialist involvement is essential for optimal integration of plozasiran into clinical practice. With 2 FDA-approved therapies, clinicians now have the ability to tailor therapy based on patient characteristics, response patterns, and safety considerations.
Relevant disclosures for Ballantyne include Arrowhead Pharmaceuticals, Inois, Merck, Novartis, Novo Nordisk, New Amsterdam, Esperion, AstraZeneca, Eli Lilly, and others. Relevant disclosures for Le include Amarin, Bayer, Esperion, Idorsia, Janssen, Novo Nordisk, Novartis, Lexicon Pharmaceuticals, and Pfizer.
