Experts: How Plozasiran Is Transforming Care for Rare Lipid Disorders

In an interview with Pharmacy Times, On Chen, MD, clinical associate professor in medicine at Stony Brook Medicine, and Tahmid Rahman, MD, associate director of the Center for Advanced Lipid Management at Stony Brook Medicine, discussed the world’s first commercial administration of plozasiran (Redemplo; Arrowhead Pharmaceuticals), which took place at their center, and its significance for patients with familial chylomicronemia syndrome (FCS).

“Up until now, we had limited tools in our arsenal to deal with this condition, so having a medication that can dramatically reduce triglycerides is very exciting.” - On Chen, MD

Chen explained that FCS is a rare genetic disorder characterized by extreme triglyceride accumulation due to impaired triglyceride metabolism. This buildup significantly increases the risk of recurrent pancreatitis, which can severely affect quality of life and long-term health outcomes. Historically, treatment options have been limited, leaving clinicians with few effective tools to manage this high-risk population.

Chen emphasized that the approval of plozasiran represents a major therapeutic advancement, offering a targeted approach to dramatically lower triglyceride levels. He noted that this development is especially meaningful for patients who have lived with the burden of recurrent pancreatitis and restrictive lifestyle measures due to the lack of effective therapies. For pharmacists, this shift highlights the importance of understanding rare lipid disorders and the evolving treatment landscape to support patient education and medication management.

Rahman detailed how plozasiran differs mechanistically from traditional lipid-lowering agents such as fibrates and omega-3 fatty acids. Unlike therapies that act on cell surface receptors and enzymes, plozasiran is a small interfering RNA (siRNA) therapy that works at the genetic level. The drug inhibits the production of apolipoprotein C-III (ApoC-III), a protein that suppresses lipoprotein lipase activity. By blocking ApoC-III synthesis, plozasiran restores lipoprotein lipase function, enabling enhanced breakdown of triglyceride-rich particles such as chylomicrons.

This novel mechanism underscores a paradigm shift toward precision medicine in lipid management. For pharmacists, familiarity with RNA-based therapies is increasingly important, particularly for counseling patients on administration, monitoring expectations, and adherence. As new agents emerge, pharmacists will play a critical role in optimizing therapy, ensuring safety, and supporting interdisciplinary care for patients with rare metabolic disorders.