Arrowhead Pharmaceuticals Secures Positive CHMP Recommendation for REDEMPLO® (plozasiran) to Treat Elevated Triglycerides in Adults with Familial Chylomicronemia Syndrome in Europe
Arrowhead Pharmaceuticals has taken a significant step forward in advancing treatment options for patients living with the rare and often debilitating condition Familial Chylomicronemia Syndrome (FCS), announcing that the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of REDEMPLO® (plozasiran). The therapy, a novel small interfering RNA (siRNA) medicine, is designed to reduce triglyceride levels when used alongside dietary management in adult patients diagnosed with FCS. This recommendation marks a pivotal regulatory milestone and sets the stage for a final decision by the European Commission, expected in the second quarter of 2026.
If granted marketing authorization, REDEMPLO would become the first siRNA-based therapy approved in the European Union for both genetically confirmed and clinically diagnosed adult patients with FCS. This distinction is particularly important in a disease area where diagnostic barriers remain significant. FCS is estimated to affect between one and thirteen individuals per million worldwide, yet it remains widely underdiagnosed due to its rarity and the complexity of confirming the condition through genetic testing. By not requiring genetic confirmation for treatment eligibility, plozasiran could broaden access to therapy for a larger segment of patients who might otherwise remain untreated.
FCS is characterized by extremely elevated triglyceride levels, often reaching levels many times higher than what is considered normal. These dangerously high lipid levels predispose patients to recurrent episodes of acute pancreatitis, a painful and potentially life-threatening condition. Over time, repeated pancreatitis attacks can result in long-term complications, including pancreatic damage and increased mortality risk. Current management strategies rely heavily on strict dietary fat restriction, which can be difficult to maintain and often insufficient in controlling triglyceride levels. As a result, there remains a substantial unmet medical need for effective pharmacological interventions.
The CHMP’s recommendation was supported by compelling data from the Phase 3 PALISADE clinical trial, a randomized, double-blind, placebo-controlled study that evaluated the efficacy and safety of plozasiran in adults with either clinically diagnosed or genetically confirmed FCS. The study successfully met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in triglyceride levels compared to placebo. In the trial, patients receiving a 25 mg dose of REDEMPLO experienced a median triglyceride reduction of 80% from baseline, compared to a 17% reduction observed in the placebo group.
Beyond triglyceride reduction, the PALISADE study also achieved all multiplicity-controlled key secondary endpoints. These included significant decreases in levels of apolipoprotein C-III (apoC-III) and a reduction in the incidence of acute pancreatitis episodes among treated patients. The reduction in pancreatitis risk is particularly noteworthy, as preventing these episodes is a central goal in managing FCS and improving patient outcomes.
Plozasiran’s mechanism of action is rooted in the science of RNA interference, a biological process that enables the targeted silencing of specific genes. Utilizing Arrowhead’s proprietary Targeted RNAi Molecule (TRiM™) platform, the therapy is designed to inhibit the production of apoC-III, a protein that plays a crucial role in regulating triglyceride metabolism. ApoC-III acts as an inhibitor of triglyceride breakdown and clearance, leading to elevated triglyceride levels when present in excess. By silencing the messenger RNA responsible for producing apoC-III, plozasiran effectively reduces its levels, thereby promoting the clearance of triglycerides from the bloodstream.
This targeted approach is supported by genetic evidence showing that individuals with naturally occurring loss-of-function mutations in the APOC3 gene tend to have significantly lower triglyceride levels and a reduced risk of developing atherosclerotic cardiovascular disease. These findings provide a strong biological rationale for targeting apoC-III as a therapeutic strategy.
From a patient convenience standpoint, REDEMPLO offers a relatively infrequent dosing schedule, being administered as a subcutaneous injection once every three months. This quarterly dosing regimen may improve adherence compared to therapies requiring more frequent administration, particularly in a chronic condition like FCS that requires lifelong management.
In terms of safety, the therapy demonstrated a tolerable profile in clinical trials. The most commonly reported adverse reactions included hyperglycaemia (12.8%), headache (6.8%), nausea (4.7%), and injection site reactions (4.7%). While these side effects are notable, they were generally manageable and consistent with expectations for therapies in this class.
Commenting on the CHMP’s positive opinion, Christopher Anzalone, President and CEO of Arrowhead Pharmaceuticals, emphasized the significance of this milestone. He noted that the recommendation reflects the strength of the clinical data supporting REDEMPLO and highlights the potential of the company’s TRiM platform to deliver targeted RNAi therapies across multiple disease areas. Anzalone also underscored the company’s commitment to working closely with regulatory authorities and the broader healthcare community to bring this therapy to patients across Europe as quickly as possible.
Clinical experts have also expressed optimism about the potential impact of plozasiran. Gerald F Watts, Professor of Cardio-metabolic Medicine at the University of Western Australia, highlighted the substantial burden faced by patients with FCS and the limitations of existing treatment options. He described the results of the PALISADE study as demonstrating both substantial and sustained reductions in triglyceride levels, as well as a meaningful reduction in pancreatitis risk. According to Watts, plozasiran represents a major advancement in the care of FCS and could significantly expand treatment options for patients across Europe.
The broader scientific and medical community has also taken note of the PALISADE findings. The study’s results were presented at major international conferences, including the European Society of Cardiology Congress 2024 and the American Heart Association Scientific Sessions 2024, underscoring the importance of the data within the cardiovascular and metabolic disease fields. Additionally, the results were published in leading peer-reviewed journals such as The New England Journal of Medicine and Circulation, further validating the robustness of the findings.
Regulatory recognition of REDEMPLO’s potential has extended beyond Europe. The therapy has already received approvals in the United States, Canada, and China, reflecting a growing global consensus حول its clinical value. In the United States, the U.S. Food and Drug Administration has granted plozasiran multiple designations, including Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation. These designations are intended to expedite the development and review of therapies that address serious conditions and fulfill unmet medical needs.
Similarly, the EMA has granted Orphan Designation to REDEMPLO, recognizing the rarity of FCS and the need for innovative treatments. Orphan designation provides incentives such as market exclusivity and regulatory support, which can facilitate the development and commercialization of therapies for rare diseases.
As Arrowhead continues to expand its global footprint, the potential approval of REDEMPLO in the European Union would represent a critical step in improving access to care for patients with FCS. By offering a novel mechanism of action, significant efficacy in reducing triglycerides, and the potential to lower pancreatitis risk, plozasiran could redefine the treatment landscape for this challenging condition.
Looking ahead, the anticipated decision by the European Commission will be closely watched by clinicians, patients, and industry stakeholders alike. A positive outcome would not only validate the promise of RNA interference as a therapeutic modality but also reinforce the importance of innovation in addressing rare and underserved diseases. For patients living with FCS, many of whom face a lifetime of dietary restrictions and the constant threat of pancreatitis, REDEMPLO could represent a transformative new option that meaningfully improves both clinical outcomes and quality of life.
About FCS
Familial chylomicronemia syndrome (FCS) is a severe and rare disease leading to extremely high triglyceride (TG) levels, typically over 10 mmol/L (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.
About the PALISADE Phase 3 Study
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.
About REDEMPLO® (plozasiran)
REDEMPLO (plozasiran) is the first and only siRNA treatment approved in these countries that has been studied in both genetically confirmed and clinically diagnosed patients living with FCS. REDEMPLO is a first-in-class 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 self-administered via subcutaneous injection once every three months.
The EMA CHMP has adopted a positive opinion recommending the European Marketing Authorization of REDEMPLO (plozasiran), which is already approved by the U.S. Food and Drug Administration, Health Canada, and China’s National Medical Products Administration as an adjunct to diet to reduce triglycerides for adults with Familial Chylomicronemia Syndrome (FCS).
In addition to approvals of REDEMPLO in the U.S., Canada, and China, plozasiran has been submitted to additional global regulatory authorities for review and marketing authorization. Plozasiran is also being investigated in the SHASTA-3 (NCT06347003), SHASTA-4 (NCT06347016), and SHASTA-5 (NCT06880770) Phase 3 studies in adults with severe hypertriglyceridemia and the MUIR-3 (NCT06347133) Phase 3 study in adults with hypertriglyceridemia. In December 2025, plozasiran was granted Breakthrough Therapy designation by the U.S. FDA in severe hypertriglyceridemia.
About Arrowhead Pharmaceuticals
Arrowhead Pharmaceuticals (NASDAQ: ARWR) is a commercial-stage pharmaceutical company developing medicines that treat intractable diseases by silencing the genes that cause them, harnessing the natural RNA interference (RNAi) mechanism. The company has built a broad portfolio of clinical and commercial RNAi therapeutics through its industry-leading targeted RNAi molecule (TRiM™) platform, which can precisely silence genes in a wide range of cell types, including liver, lung, muscle, adipose, and central nervous system tissue. At Arrowhead, we rapidly advance potential best- and first-in-class RNAi treatments for diseases with significant unmet medical need, because every day matters to the patients we serve.
Source Link:https://www.businesswire.com/
