FDA Approves Redemplo (Plozasiran) to Lower Triglycerides in Adults with Familial Chylomicronemia Syndrome: First siRNA Therapy Offering Hope to Rare Disease Patients

On November 17, 2025, the U.S. Food and Drug Administration (FDA) granted approval to Redemplo (Plozasiran), an innovative siRNA therapy developed by Arrowhead Pharmaceuticals. It is the first FDA-approved medication specifically indicated to reduce triglyceride levels in adults with familial chylomicronemia syndrome (FCS), a rare and potentially life-threatening genetic lipid disorder characterized by extremely high triglyceride levels due to lipoprotein lipase defects. Redemplo is approved as an adjunct to a low-fat diet to help manage this complex condition.

FCS is a hereditary disorder with genetic mutations affecting the metabolism of chylomicrons, leading to persistent and severe hypertriglyceridemia. Patients suffer from complications including recurrent and potentially fatal acute pancreatitis, as well as symptoms such as severe abdominal pain and brain fog. For years, treatment options have mainly relied on strict dietary fat restrictions with limited pharmacologic interventions available.

Plozasiran is a subcutaneously administered small interfering RNA (siRNA) designed to specifically target and silences the gene encoding apolipoprotein C-III (apoC-III). ApoC-III is a critical regulator that inhibits the breakdown of triglyceride-rich lipoproteins. By reducing apoC-III production, Redemplo enhances triglyceride clearance from the blood, resulting in marked reductions in triglyceride levels.

The FDA approval was supported by data from the randomized, placebo-controlled phase 3 PALISADE trial (NCT05089084). This study enrolled adults with genetically confirmed or clinically diagnosed FCS, all maintained on a low-fat diet. Patients received subcutaneous injections of Plozasiran (25 mg or 50 mg) or placebo every three months for 12 months.

Key findings included a median 80% reduction in fasting triglyceride levels at 10 months with 25 mg Plozasiran versus placebo (17% reduction). Durable triglyceride lowering effects sustained through 12 months. Significant reductions in the risk of acute pancreatitis and improvements in quality of life measures associated with symptom relief.

Common adverse events were mild and included abdominal pain, headache, nasopharyngitis, and nausea. There were no severe safety concerns such as thrombocytopenia observed.

Plozasiran showed a generally favorable safety and tolerability profile. Some patients with prediabetes or diabetes experienced hyperglycemia. Minor transient increases in liver enzymes were noted but did not lead to treatment discontinuation. Unlike some other therapies, thrombocytopenia was not observed.

The efficacy and safety results from the PALISADE study of Plozasiran (Redemplo) were presented at the various conferences and conclaves and simultaneously published in The New England Journal of Medicine and Circulation.

Lindsey Sutton Bryan, co-founder and co-president of the FCS Foundation, stated that the FDA approval of Plozasiran marks a pivotal moment for people with familial chylomicronemia syndrome, a community often overlooked due to invisible symptoms. She expressed gratitude to Arrowhead for incorporating patient experiences into developing this transformative therapy, offering real hope for a better future.

Christopher Anzalone, Ph.D., President and CEO of Arrowhead Pharmaceuticals, called the FDA approval of REDEMPLO a transformational milestone and a proud achievement for the development team. He highlighted that this first FDA approval using Arrowhead’s TRiM™ platform opens new possibilities for addressing multiple diseases and improving many lives through advanced siRNA therapies.

Arrowhead Pharmaceuticals’ Targeted RNAi Molecule (TRiM™) platform is a cutting-edge technology designed to deliver RNA interference (RNAi) therapies with high precision to specific tissues. It simplifies the RNA molecule structure while enhancing targeting, potency, and pharmacokinetics, enabling effective and durable gene silencing. This platform allows Arrowhead to develop innovative therapies with reduced manufacturing complexity and expanded potential to target diseases beyond the liver, including lung and tumors.