FDA Approves Plozasiran for Adults With Familial Chylomicronemia Syndrome

Announced by Arrowhead Pharmaceuticals on November 18, 2025, the US Food and Drug Administration has approved plozasiran under the brand name REDEMPLO for the reduction of triglycerides in adult patients with familial chylomicronemia syndrome (FCS).1

"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. "Because FCS symptoms are mostly invisible, this community historically has been often overlooked and misunderstood, making their journey to effective treatment especially difficult."1

Plozasiran, a first-in-class investigational RNA interference therapeutic, is designed to reduce apoC-III production. ApoC-III is a major component of triglyceride-rich lipoproteins (TRLs) and a regulator of triglyceride metabolism, as it increases triglyceride levels in the blood by preventing breakdown of TRLs by lipoprotein lipase and the uptake of TRL remnants by hepatic receptors in the liver.2

The FDA accepted plozasiran’s New Drug Application (NDA) on January 17, 2025, based on results from the PALISADE phase 3 trial. The application also included supportive evidence from the phase 2 SUMMIT program. PALISADE met its primary endpoint and all multiplicity-controlled key secondary endpoints, including statistically significant reductions in triglycerides, apoC-III, and acute pancreatitis incidence.2

Investigators in the PALISADE trial included patients who had a fasting triglyceride level ≥880 mg/dL at screening refractory to standard lipid lowering therapy, as well as a diagnosis of FCS, who were willing to follow dietary counseling based on investigator judgment and local standard of care. Patients were excluded if they were using or had used any hepatocyte-targeted siRNA or antisense oligonucleotide molecules within the last 365 days, if they had diabetes mellitus newly diagnosed or active pancreatitis within 12 weeks before screening, if they had uncontrolled hypertension, or if they had New York Heart Association Class II, III, or IV heart failure, among other criteria.3

A total of 75 participants were enrolled in PALISADE, and were randomly assigned to either 25 mg plozasiran, 50 mg plozasiran, or matching placebo, all of which were administered once every 3 months. The primary endpoint was the percent change from baseline in fasting triglycerides at month 10. Secondary endpoints included an average of the percent change from baseline in fasting triglycerides at months 10 and 12, as well as percent changes in apoC-III and non-HDL-C at months 10 and 12.3

Ultimately, patients in the 25 mg arm saw a median change in triglycerides from baseline of 80% and an 83% decreased risk of acute pancreatitis versus placebo in the pooled plozasiran 25 mg and 50 mg group. Investigators also reported a favorable tolerability profile throughout the trial. The 25 mg dose also saw only the adverse events of abdominal pain, nasopharyngitis, nausea, and COVID-19.2

"The FDA approval of REDEMPLO is a transformational milestone for Arrowhead. This is a proud moment for all those involved in the discovery and development process and represents new hope for the estimated 6500 people in the US living with genetic or clinical FCS," Christopher Anzalone, PhD, president and chief executive officer at Arrowhead Pharmaceuticals, said in a statement.1

In a press release, Arrowhead Pharmaceuticals has confirmed that plozasiran will be available in the US before the end of 2025.1

References

1. Anzalone V. Arrowhead Pharmaceuticals Announces FDA Approval of REDEMPLO (plozasiran) to Reduce Triglycerides in Adults with Familial Chylomicronemia Syndrome (FCS). BusinessWire. November 18, 2025. Accessed November 18, 2025. https://www.businesswire.com/news/home/20251112678197/en/Arrowhead-Pharmaceuticals-Announces-FDA-Approval-of-REDEMPLO-plozasiran-to-Reduce-Triglycerides-in-Adults-with-Familial-Chylomicronemia-Syndrome-FCS

2. Anzalone V. Arrowhead Pharmaceuticals Announces Acceptance of New Drug Application by U.S. FDA of Plozasiran for the Treatment of Familial Chylomicronemia Syndrome. Arrowhead Pharmaceuticals Newsroom. January 17, 2025. Accessed November 17, 2025. https://arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-announces-acceptance-of-new-drug-application-by-u-s-fda-of-plozasiran-for-the-treatment-of-familial-chylomicronemia-syndrome/

3. Arrowhead Pharmaceuticals. Study of ARO-APOC3 (Plozasiran) in Adults With Familial Chylomicronemia Syndrome (FCS) (PALISADE). ClinicalTrials.gov Identifier: NCT05089084. Updated April 30, 2025. Accessed November 17, 2025. https://clinicaltrials.gov/study/NCT05089084