FDA Approves Plozasiran to Reduce Triglycerides in Familial Chylomicronemia Syndrome

The FDA today approved plozasiran (Redemplo; Arrowhead Pharmaceuticals) for the treatment of adults with familial chylomicronemia syndrome (FCS).1 The small interfering RNA (siRNA) medicine is the first FDA-approved drug for individuals with FCS and is indicated as an adjunct to diet to reduce triglycerides in this patient population.

Plozasiran's approval, the first for manufacturer Arrowhead Pharmaceuticals, was supported by results of the phase 3 PALISADE trial (NCT05089084), which met its primary end point and all multiplicity-controlled key secondary end points.

Plozasiran was approved for adults with familial chylomicronemia syndrome. | Image credit: wladimir1804 - stock.adobe.com

In the PALISADE study, patients who received 25 mg of subcutaneous plozasiran every 3 months showed deep and durable triglyceride level reduction, which was the study's primary end point. The median change in fasting triglyceride levels from baseline to 10 months was −80% in the 25-mg plozasiran group, −78% in the 50-mg plozasiran group, and −17% in the placebo group (P < .001).2

Patients with FCS often have persistent and severe hypertriglyceridemia, which significantly increases their risk for acute, recurrent, and potentially fatal pancreatitis in addition to overlapping symptoms like severe brain fog or recurrent abdominal pain, causing delays to diagnosis.1,3

The PALISADE study met its secondary end points as well, demonstrating a significant reduction in triglycerides from baseline to the mean values at 10 months and 12 months. The median reduction in triglyceride levels was approximately 59% in the 25-mg group and 53% in the 50-mg group compared with the placebo. Additionally, researchers observed better results in the plozasirin group when compared with the placebo group for the incidence of acute pancreatitis (OR, 0.17; 95% CI, 0.03-0.94; P = .03).2

“Today’s approval marks a pivotal moment for people living with familial chylomicronemia syndrome and the physicians who support them," Lindsey Sutton Bryan, co-founder and co-president of the FCS Foundation, said in a statement.1 "Because FCS symptoms are mostly invisible, this community has historically been often overlooked and misunderstood, making their journey to effective treatment especially difficult.

Safety and Efficacy of Plozasorin

The most common adverse events (AEs) in the study were abdominal pain, nasopharyngitis, headache, and nausea, with severe or serious AEs less common among the plozasiran vs placebo population. Some patients with prediabetes or diabetes at baseline experienced hyperglycemia with plozasiran. Thrombocytopenia, a common AE with other therapies for FCS, was not observed; however, minor transient increases in liver enzymes occurred without leading to dose discontinuation.

"We’re grateful to Arrowhead for listening to patients and caregivers and incorporating their lived experiences into the development of this transformative therapy," Bryan said. "Plozasiran offers real hope for a better future and shows what’s possible when innovation is driven by empathy and collaboration, addressing patients in need.”

References

1. Arrowhead Pharmaceuticals announces FDA approval of Redemplo (plozasiran) to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). News release. Arrowhead Pharmaceuticals. November 18, 2025. Accessed November 18, 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. Watts GF, Rosenson RS, Hegele RA, et al. Plozasiran for managing persistent chylomicronemia and pancreatitis risk. N Engl J Med. 2025;392(2):127-137. doi:10.1056/NEJMoa2409368

3. Arrowhead Pharmaceuticals, Inc. Corporate Presentation. Arrowhead Pharmaceuticals; 2025. Accessed November 18, 2025. https://ir.arrowheadpharma.com/static-files/281fb439-ad42-4e18-a87f-75be0b91fce6