MON-276 - Real-World Use of Olezarsen at the University of Pennsylvania Health Systems

Olezarsen is an antisense oligonucleotide that reduces triglyceride (TG) levels by targeting the APOC3 mRNA, which encodes for apolipoprotein CIII (apoC-III), a key regulator of TG metabolism. It is recently FDA-approved for patients with Familial Chylomicronemia Syndrome (FCS), a condition of severe hypertriglyceridemia with high risk for acute pancreatitis. Olezarsen is administered via subcutaneous injection every 4 weeks and has been previously shown to lower triglycerides by ~ 50% in patients with genetically confirmed FCS.

In this review, we present real-world data on the effectiveness and safety of olezarsen in patients seen at the University of Pennsylvania Health Systems (UPHS). Our objective is to describe the demographics of patients prescribed olezarsen at UPHS and to explore the safety and effectiveness of olezarsen in lowering TGs.

A retrospective review of electronic medical records for patients prescribed olezarsen at UPHS was performed following the date of FDA-approval in December 2024 through January 2026. Demographics, clinical presentation, lipid-lowering therapies, and clinical lab results at baseline and throughout use of olezarsen were collected for analysis. This study was approved by the Penn IRB.

A total of 5 patients (80% female, 80% white) were prescribed and completed at least one dose of olezarsen at a mean age of 65.6 years (range: 48 to 81 years old). Of these patients, 66.6% (n=3) were diagnosed with FCS via genetic testing showing biallelic pathogenic variants in LPL or related genes. 4 patients had a history of recurrent acute pancreatitis episodes prior to starting olezarsen. At the time of prescription, 80% of the patients were on statins, 80% were on fibrates, 40% were on ezetimibe, and 40% were on omega-3 fatty acids. Mean (± SD) TG levels were 1326.8 ± 950.90 mg/dL at baseline, and after an average of 8 doses (range: 4 to 10 doses) of olezarsen, the mean TG level was lowered to 586.2 ± 633.98 mg/dL. Two patients experienced a single acute pancreatitis event after initiating olezarsen. Liver transaminases (ALT and AST) remained < 2x ULN in all patients. No patients discontinued from treatment during the study period.

Data collected at this large academic medical center shows the effectiveness of olezarsen to lower TGs in patients with FCS and is well-tolerated.

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