Arrowhead Pharmaceuticals Announces FDA Approval of REDEMPLO® (plozasiran), Marking a Major Advancement in Treatment for Familial Chylomicronemia Syndrome
Arrowhead Pharmaceuticals, Inc. (NASDAQ: ARWR) announced a landmark achievement today with the U.S. Food and Drug Administration’s (FDA) approval of REDEMPLO® (plozasiran). This small interfering RNA (siRNA) medicine is now authorized as an adjunct to diet to reduce triglyceride levels in adults diagnosed with familial chylomicronemia syndrome (FCS)—a life-threatening, ultra-rare genetic disorder characterized by extraordinarily elevated triglycerides and a heightened risk of severe recurrent pancreatitis. The approval marks not only a breakthrough for the FCS community but also the first-ever FDA approval for an Arrowhead-developed therapy utilizing the company’s proprietary Targeted RNAi Molecule (TRiM™) platform.
FCS, a severely debilitating metabolic disease, affects an estimated 6,500 individuals in the United States. People with FCS have triglyceride levels that can reach 10 to 100 times higher than normal, leading to significant morbidity. These extreme lipid elevations place individuals at persistent risk for acute and recurrent pancreatitis, an inflammatory condition that can be extremely painful, medically complex, and even fatal. Managing FCS has long been challenging due to limited therapeutic options, strict dietary restrictions, and inconsistent treatment response. The approval of REDEMPLO introduces a new therapeutic approach and a meaningful opportunity for improved disease control.
A New Era in RNAi Therapeutics for FCS
REDEMPLO is the first and only FDA-approved siRNA therapy specifically for individuals living with FCS. With a convenient subcutaneous injection once every three months, REDEMPLO offers ease of use and can be self-administered at home, eliminating the need for ongoing clinic visits and reducing treatment burden for patients and families who already manage significant daily challenges.
The therapy is built on Arrowhead’s TRiM™ platform, a versatile and differentiated RNA interference delivery system designed to target specific genes involved in disease pathways. For FCS, REDEMPLO acts by silencing the expression of apolipoprotein C-III (APOC3), a critical protein involved in regulating triglyceride metabolism. Reducing APOC3 levels effectively decreases triglyceride levels and may lower the risk of pancreatitis—a meaningful goal for individuals whose daily lives are affected by unpredictable and debilitating disease episodes.
Arrowhead President and CEO, Christopher Anzalone, Ph.D., described the FDA decision as an extraordinary milestone for the Arrowhead company and a life-changing moment for patients. “The FDA approval of REDEMPLO is a transformational milestone for Arrowhead,” he shared. “It represents a proud moment for everyone involved in its discovery and development. More importantly, it brings new hope to the estimated 6,500 people in the U.S. living with FCS, many of whom have endured years of limited treatment options and significant impact on quality of life.”
Dr. Anzalone also emphasized that this regulatory success validates the tremendous potential of the TRiM™ platform. “This is the first FDA approval for a medicine leveraging Arrowhead’s proprietary TRiM™ technology, and it showcases what’s possible when scientific innovation aligns with patient need. Today, our TRiM™ platform can potentially deliver siRNA to seven different cell types throughout the body, and future programs may even silence two genes simultaneously in a single therapeutic construct. These capabilities dramatically expand the range of diseases we may be able to address.”
Compelling Evidence from the Phase 3 PALISADE Study
The FDA’s approval of REDEMPLO was supported by robust data from the Phase 3 PALISADE clinical trial, a randomized, double-blind, placebo-controlled, multicenter study that enrolled adults with genetically confirmed or clinically diagnosed FCS. PALISADE met its primary endpoint as well as all multiplicity-controlled key secondary endpoints, providing strong evidence of the therapy’s efficacy and safety.
In the study, REDEMPLO at the 25 mg dose achieved deep and durable reductions in triglycerides, with a median reduction of 80% from baseline. In contrast, the pooled placebo group experienced a modest 17% reduction. These dramatic improvements highlight the ability of REDEMPLO to target the underlying biology of FCS, resulting in meaningful and consistent triglyceride lowering.
Notably, the trial also observed a numerically lower incidence of acute pancreatitis in patients treated with REDEMPLO compared to those on placebo. While the study was not powered specifically to evaluate pancreatitis risk reduction, this finding aligns with the known association between lower triglyceride levels and reduced pancreatitis events—suggesting potential added clinical benefit for individuals living with the condition.
PALISADE results were shared at two major international cardiology conferences: the European Society of Cardiology (ESC) Congress 2024 and the American Heart Association (AHA) Scientific Sessions 2024 (AHA24). Additionally, the primary data were published in two leading peer-reviewed medical journals—The New England Journal of Medicine and Circulation—solidifying the trial’s scientific impact and the therapy’s clinical significance. More detailed presentations and supplemental materials can be accessed on the Arrowhead Pharmaceuticals website under the Investors section.
Patient Community Reaction: A Long-Awaited Breakthrough
For the FCS patient community, the FDA approval of REDEMPLO represents a turning point after decades of unmet need. Lindsey Sutton Bryan, co-founder and co-president of the FCS Foundation, described the moment as “pivotal” for affected families and clinicians.
“Because the symptoms of FCS are often invisible, this community has long been overlooked and misunderstood,” she said. “The journey to effective treatment has been especially difficult, marked by uncertainty, severe pancreatitis episodes, strict dietary limitations, and emotional strain. We’re deeply grateful to Arrowhead for listening to patients and caregivers, learning from their lived experiences, and incorporating their feedback into the design and refinement of this therapy. Plozasiran offers real hope for a better future and demonstrates what’s possible when innovation is guided by empathy, collaboration, and an understanding of patient needs.”
Safety Profile and Regulatory Status
REDEMPLO demonstrated an encouraging safety profile in clinical studies. The most common adverse reactions—occurring in at least 10% of REDEMPLO-treated patients and at a rate at least 5% greater than placebo—were hyperglycemia, headache, nausea, and injection site reactions. Importantly, the U.S. prescribing information contains no contraindications, warnings, or precautions, providing further reassurance about the therapy’s safety and tolerability.
The compound previously received multiple designations from the FDA, signaling the agency’s recognition of its potential to address an urgent unmet medical need. These include:
- Breakthrough Therapy Designation
- Fast Track Designation
- Orphan Drug Designation
Additionally, the European Medicines Agency (EMA) granted Orphan Medicinal Product Designation, supporting continued global development.
Patient Support and Access: Introducing Rely On REDEMPLO
Arrowhead emphasized its commitment not only to scientific innovation but also to ensuring that patients have meaningful access to the therapy. To support individuals prescribed REDEMPLO, the company is launching Rely On REDEMPLO, a comprehensive patient support program designed to assist patients throughout their treatment journey.
The program will offer a wide range of services, including:
- Education about FCS and REDEMPLO therapy
- Personalized support from dedicated case managers
- Reimbursement and access navigation
- Financial assistance for eligible patients
- Ongoing resources to support long-term treatment success
This program reflects Arrowhead’s broader mission to integrate patient-centric support with cutting-edge therapeutic development, ensuring the benefits of innovation reach those who need them most.
Commercial Availability and Next Steps
Arrowhead confirmed that REDEMPLO will be commercially available in the United States before the end of the year, marking the company’s transition into a fully integrated, commercial-stage biotechnology organization. With its first FDA approval now secured, Arrowhead anticipates further expansion of its TRiM™ pipeline into additional therapeutic areas, including cardiometabolic diseases, genetic disorders, and more.
Conference Call and Webcast Details
To discuss the FDA approval in detail, Arrowhead will host a conference call and webcast today at 1:30 p.m. ET. The live webcast will be accessible through the Events and Presentations section of the Investors page on the Arrowhead website. A replay will be available approximately two hours after the call concludes, ensuring investors, analysts, and community members have access to the discussion.
bout FCS
Familial chylomicronemia syndrome (FCS) is a severe and rare disease leading to extremely high triglyceride (TG) levels, typically over 880 mg/dL. Such severe elevations can lead to various serious signs and symptoms including acute and potentially fatal pancreatitis, chronic abdominal pain, diabetes, hepatic steatosis, and cognitive issues. Currently, there are limited therapeutic options to adequately treat FCS.
The PALISADE study (NCT05089084) was a Phase 3 placebo-controlled study to evaluate the efficacy and safety of plozasiran in adults with genetically confirmed or clinically diagnosed FCS. The primary endpoint of the study was percent change from baseline in fasting TG versus placebo at Month 10. A total of 75 subjects distributed across 39 different sites in 18 countries were randomized to receive 25 mg plozasiran, 50 mg plozasiran, or matching placebo once every three months. Participants who completed the randomized period were eligible to continue in a 2-part extension period, where all participants receive plozasiran.
REDEMPLO (plozasiran) is approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides for adults with Familial Chylomicronemia Syndrome (FCS). REDEMPLO is an siRNA therapeutic designed to suppress the production of apoC-III, a protein produced in the liver that raises triglyceride levels by slowing their breakdown and clearance. By targeting apoC-III with sustained silencing, REDEMPLO delivers significant reductions in triglyceride levels. REDEMPLO is the first and only siRNA FDA-approved treatment studied in both genetically confirmed and clinically diagnosed patients living with FCS. For more information about REDEMPLO, visit Our Medicines.
Source Link: https://www.businesswire.com/
