RX Review: Updates and Unmet Needs for Familial Chylomicronemia Syndrome

As a result of advances in pathophysiology and pharmacotherapy, cardiologists managing familial chylomicronemia syndrome (FCS) find themselves in the midst of a renaissance. Just a year before the US Food and Drug Administration approval of plozasiran (Redemplo), the condition was without any approved therapies. Now, with a pair of APOC3-targeting agents in their armamentarium, the prognosis for patients has begun to shift.

In this 7-part video series, leading experts break down what recent changes in therapeutic options mean for patients and cardiologists. In the opening segment, 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, to set the stage for a detailed discussion of FCS in 2025 and beyond.

Ballantyne highlights how FCS remains among the most difficult genetic lipid diseases to manage, given its hallmark features of extreme hypertriglyceridemia, chylomicronemia, and high risk for recurrent pancreatitis. The segment begins by grounding the audience in the reality that FCS has historically been defined more by its limitations in treatment than by its therapeutic successes.

The conversation turns to the gaps persisting before this year, underscoring how patients with FCS relied on strict dietary intervention as their primary therapy. Ballantyne notes while many individuals with elevated triglyceride levels respond to standard pharmacologic therapies, including fibrates and omega-3 fatty acids, those with FCS usually achieve little or no improvement. He describes how this lack of response stems from the genetic impairment in lipoprotein lipase function defines the disorder. The rarity of FCS further complicates diagnosis and treatment because most clinicians encounter only a few cases, if any, across their careers. Limited awareness often leads to delayed or missed diagnoses and prolonged exposure to severe metabolic instability.

The segment concludes by emphasizing 2025 marks a turning point for FCS. With the FDA approval of plozasiran on November 18, 2025 coming less than a year after the landmark approval of olezarsen in late 2024, clinicians now have access to targeted therapies capable of producing substantial triglyceride reductions. Le and Ballantyne note these approvals represent major progress, but significant work remains to improve recognition, diagnosis, and comprehensive care.

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.

References:

Arrowhead Pharmaceuticals. Arrowhead Pharmaceuticals Announces FDA Approval of REDEMPLO® (plozasiran) to Reduce Triglycerides in Adults with Familial Chylomicronemia Syndrome (FCS) - Arrowhead Pharmaceuticals, Inc. Arrowhead Pharmaceuticals, Inc. Published November 19, 2025. Accessed November 25, 2025. https://arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-announces-fda-approval-of-redemplo-plozasiran-to-reduce-triglycerides-in-adults-with-familial-chylomicronemia-syndrome-fcs/.

Virani SS, Morris PB, Agarwala A, et al. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021;78(9):960-993. doi:10.1016/j.jacc.2021.06.011

US Food and Drug Administration. FDA approves Tryngolza (olezarsen). U.S. Food and Drug Administration. Published December 19, 2024. Accessed November 25, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-reduce-triglycerides-adult-patients-familial-chylomicronemia-syndrome.