RX Review: Updates in Diagnosis and Testing for FCS

As the cardiology community attempts to embrace a new era of management for familial chylomicronemia syndrome (FCS), discussions have begun to shift towards improvement of diagnosis and testing for the rare lipid disorder.

In part 3 of our 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, and panelist Christie Ballantyne, MD, chief of cardiovascular research at Baylor College of Medicine and principal investigator of the PALISADE trial, begin by describing the current diagnostic framework for FCS.

Ballantyne explains diagnosis relies on the integration of genetic testing and structured clinical evaluation. Genetic testing remains the gold standard for confirming pathogenic variants in genes impairing lipoprotein lipase function, yet access to testing varies widely across regions and clinical settings. While genetic confirmation is ideal, Ballantyne notes clinicians often must make early decisions before results are available. This is especially relevant in contexts where treatment initiation may be time-sensitive, such as preventing recurrent pancreatitis or meeting payer requirements.

The conversation turns to validated scoring systems support the diagnostic process. Ballantyne outlines the North American and European clinical scoring frameworks, which assess features such as age of onset, severity of triglyceride elevation, response to prior therapies, and exclusion of secondary causes. These tools are designed to differentiate FCS from multifactorial hypertriglyceridemia, which has a far higher prevalence. The speakers emphasize clear documentation within these frameworks helps clinicians navigate payer review, which is increasingly important following the approvals of plozasiran (Redemplo) and olezarsen (Tryngolza). Both therapies require precise diagnostic justification to ensure coverage.

The segment ends by highlighting the importance of a systematic, stepwise approach. Ballantyne notes diagnosis rarely hinges on a single finding, but rather on a coordinated interpretation of laboratory results, clinical history, and genetic data. This integrated approach speeds referral to lipid specialists and ensures that patients who qualify for newly approved therapies are identified efficiently. Le and Ballantyne emphasize robust diagnostic processes will ultimately lead to earlier intervention and better long-term outcomes.

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:

1. 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/.

2. 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

3. 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.