Plozasiran Recieves FDA Approval to Reduce Triglycerides in Adults with Familial Chylomicronemia Syndrome

The FDA has approved plozasiran (Redemplo; Arrowhead Pharmaceuticals), a small interfering RNA (siRNA) therapy designed to target apolipoprotein C-III (apoC-III), as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS).¹

As an siRNA therapy, plozasiran 25 mg/0.5 mL solution in a single-dose pre-filled syringe is administered as a subcutaneous injection into the front of the thigh or abdomen once every 3 months. The injection can also be given in the upper arm if administered by a health care provider or caregiver.²

Understanding Familial Chylomicronemia Syndrome

An estimated 1 to 2 individuals per million are impacted by FCS, marking it as a rare genetic disorder that prevents the body from breaking down fats consumed through the diet, or triglycerides. Chylomicrons are large particles that transport triglycerides through the bloodstream, delivering them to tissues for energy use and fat storage.³

Around 80% of individuals with FCS have a defect in lipoprotein lipase, the enzyme responsible for breaking down chylomicrons, which leads to their buildup and extremely high triglyceride levels. Since this enzyme is absent or not functioning properly, individuals with FCS can have triglyceride levels that often exceed 1000 mg/dL, even with medication or a low-fat diet.³

Symptoms of high triglyceride levels include severe abdominal pain, inflammation of the pancreas, and acute pancreatitis, all of which can be life-threatening. Other symptoms include lipemia retinalis and eruptive xanthomas. Signs of FCS can develop in infancy, but some patients may not experience symptoms until they are adults.³

What Does Clinical Trial Data Find?

In a randomized, placebo-controlled, double-blind phase 3 trial (NCT05089084), researchers evaluated the efficacy of plozasiran in adults with genetically confirmed or clinically diagnosed FCS that was maintained on a low-fat diet. A total of 75 patients were included and randomly assigned to receive 4 total doses of plozasiran 25 mg, 50 mg, or placebo once every 3 months over a 12-month treatment period. Across treatment groups, patients had a mean age of 46 years, about half were male, and most patients were White.^1,2,4

The trial measured the percent change in fasting triglycerides from baseline to month 10. Results demonstrated that patients treated with plozasiran showed a median 59% reduction compared with placebo.^1,2

Treatment was discontinued in 6% of plozasiran patients due to adverse reactions, including hyperglycemia and urticaria, while no discontinuation occurred in patients who received placebo. Adverse reactions occurred in at least 10% of plozasiran-treated patients and at least 5% more than with placebo. Reactions included hyperglycemia, headache, nausea, and injection site reaction.^1,2

REFERENCES

1. FDA approves drug to reduce triglycerides in adults with familial chylomicronemia syndrome. News release. FDA. November 18, 2025. Accessed November 18, 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-reduce-triglycerides-adults-familial-chylomicronemia-syndrome

2. FDA. (2025). REDEMPLO (labeling information) (NDA 219947). https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/219947s000lbl.pdf

3. Familial Chylomicronemia Syndrome. Endocrine Society. News release. January 24, 2022. Accessed November 18, 2025. https://www.endocrine.org/patient-engagement/endocrine-library/familial-chylomicronemia-syndrome

4. Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS) (PALISADE). Arrowhead Pharmaceuticals. Updated April 30, 2025. Accessed November 18, 2025. https://clinicaltrials.gov/study/NCT05089084