Arrowhead Pharmaceuticals Unveils Encouraging Clinical Cardiometabolic Findings at the 94th European Atherosclerosis Society Congress
Arrowhead Pharmaceuticals has presented new clinical findings supporting the broader use of plozasiran, its investigational small interfering RNA therapy targeting apolipoprotein C-III (APOC3), during two oral presentations at the European Atherosclerosis Society Congress 2026 held in Athens, Greece from May 24-27. The newly reported data highlighted the therapy’s pharmacokinetic and pharmacodynamic profile in patients with renal or hepatic impairment and also included a case report involving pregnancy outcomes in a patient with familial chylomicronemia syndrome (FCS).
The presentations provide additional evidence supporting plozasiran’s potential role in treating patients with severe triglyceride disorders, particularly those with significant comorbidities that often complicate long-term disease management. According to the company, the findings may help expand understanding of how plozasiran performs in medically complex patient populations frequently encountered in clinical practice.
Jennifer Hellawell, Vice President of Clinical Development at Arrowhead Pharmaceuticals and a board-certified cardiologist, stated that patients living with extremely elevated triglyceride levels often face substantial medical challenges beyond lipid abnormalities alone. She said the latest data help bridge the gap between scientific innovation and unmet patient needs by further characterizing plozasiran’s safety and efficacy profile in broader patient populations.
Hellawell noted that the new data provide additional insight into the pharmacokinetics (PK) and pharmacodynamics (PD) of plozasiran among individuals with moderate-to-severe renal impairment or moderate hepatic impairment. According to her, the findings represent another step toward delivering clinically meaningful treatment options for underserved patients with severe triglyceride disorders.
Plozasiran is an RNA interference-based therapy designed to reduce production of APOC3 in the liver. APOC3 is a protein known to play a central role in triglyceride metabolism by inhibiting triglyceride clearance from the bloodstream. Elevated APOC3 levels contribute to severe hypertriglyceridemia and are associated with increased risk of pancreatitis and cardiovascular complications.
By selectively silencing APOC3 messenger RNA, plozasiran aims to substantially reduce triglyceride levels through targeted hepatic RNA interference mechanisms. The therapy has already received regulatory approval in several countries, including the United States, China, Australia, and Canada, as an adjunct to diet for reducing triglycerides in adults with Familial Chylomicronemia Syndrome.
FCS is a rare genetic disorder characterized by extremely elevated triglyceride levels caused by impaired clearance of chylomicrons from the bloodstream. Patients with FCS frequently experience recurrent pancreatitis, abdominal pain, fatigue, and other severe complications. Because standard lipid-lowering therapies often provide limited benefit in FCS, there remains substantial demand for targeted therapies capable of producing durable triglyceride reductions.
Plozasiran is also currently being investigated in patients with severe hypertriglyceridemia (sHTG), a broader condition involving markedly elevated triglyceride levels that can arise from genetic and metabolic causes.
One of the key oral presentations focused on evaluating plozasiran in patients with hepatic or renal impairment. Patients with severe triglyceride disorders frequently present with additional metabolic complications, including hepatic steatosis, chronic kidney disease, and liver dysfunction. However, the safety and pharmacological behavior of APOC3-targeting therapies in these patient groups has not been fully established.
The study presented at the conference assessed how renal or hepatic impairment influenced the pharmacokinetics, pharmacodynamics, and safety of a single 25 mg dose of plozasiran.
Researchers observed modest increases in drug exposure among patients with moderate-to-severe renal impairment or moderate hepatic impairment compared with control populations. Despite these PK differences, the pharmacodynamic responses remained consistent across groups.
Specifically, reductions in APOC3 and triglyceride levels were similar between patients with organ impairment and control cohorts, suggesting that the therapy maintained its biological activity despite altered renal or hepatic function.
Importantly, investigators reported that plozasiran was generally safe and well tolerated throughout the study. No new safety signals emerged, and the company stated that the findings support use of the standard 25 mg dose in patients with moderate-to-severe renal impairment or moderate hepatic impairment without the need for dose adjustment.
These results may be particularly important for clinicians because patients with severe triglyceride disorders often have overlapping metabolic conditions that complicate therapeutic management. Dose adjustments for liver or kidney dysfunction can create additional treatment complexity and may limit therapeutic accessibility in some patient populations.
Arrowhead emphasized that further clinical research will still be needed to evaluate plozasiran in patients with advanced hepatic or renal disease. Nonetheless, the data provide encouraging evidence supporting broader use in patients with moderate organ impairment.
The second oral presentation featured a case report involving pregnancy in a patient with familial chylomicronemia syndrome previously treated with plozasiran. According to the company, the report suggests that preconception exposure to the therapy may have been associated with sustained triglyceride lowering throughout the duration of pregnancy.
The case represents the second reported pregnancy from the PALISADE clinical program involving FCS patients who discontinued plozasiran before conception and subsequently experienced successful pregnancies while maintaining triglyceride control.
Managing triglyceride disorders during pregnancy remains especially challenging because pregnancy itself often causes physiological increases in triglyceride levels. In women with familial chylomicronemia syndrome, these increases can become extreme and may dramatically elevate the risk of acute pancreatitis, a potentially life-threatening complication for both mother and fetus.
Treatment options during pregnancy are limited because many lipid-lowering therapies are either contraindicated or insufficiently studied in pregnant populations. As a result, severe triglyceride management during pregnancy often relies heavily on strict dietary interventions and close clinical monitoring.
The case report presented at the EAS Congress suggested that the prolonged pharmacodynamic effects of APOC3 inhibition may have contributed to sustained fasting triglyceride reductions throughout pregnancy even after discontinuation of active treatment before conception.
Although the company cautioned that additional data are needed to define the safety and efficacy of APOC3-targeted therapies during pregnancy, the findings are consistent with earlier observations from PALISADE studies demonstrating durable pharmacodynamic activity following plozasiran administration.
The PALISADE clinical program has been central to development of plozasiran in familial chylomicronemia syndrome and has previously demonstrated substantial triglyceride reductions in treated patients. The emerging pregnancy-related observations may further expand scientific understanding of how durable APOC3 suppression affects long-term triglyceride regulation.
The oral presentation on renal and hepatic impairment was delivered during the conference’s Late Breaking Clinical Abstracts session by Dr. Jennifer Hellawell. The presentation focused on the pharmacokinetic, pharmacodynamic, and safety profile of plozasiran in patients with organ impairment.
The pregnancy case report was presented by Dr. Ann Mertens during the EAS Stage, Outreach and Case Presentations session and highlighted the clinical experience of a pregnant woman with familial chylomicronemia syndrome previously treated with plozasiran.
The data presented at the conference reflect broader momentum within cardiovascular and metabolic medicine toward RNA interference therapeutics targeting lipid metabolism pathways. RNAi technologies have emerged as a promising therapeutic modality because of their ability to selectively suppress production of disease-associated proteins with potentially prolonged effects following infrequent dosing.
APOC3 inhibition has become an especially active area of development because of the protein’s central role in triglyceride metabolism and pancreatitis risk. Elevated triglycerides are increasingly recognized not only as a cardiovascular risk factor but also as a significant driver of acute pancreatitis and metabolic disease burden in certain patient populations.
Familial chylomicronemia syndrome remains one of the most severe triglyceride disorders, often requiring lifelong management strategies and intensive dietary restrictions. New therapies capable of delivering substantial and sustained triglyceride lowering may significantly improve disease management and patient quality of life.
Arrowhead’s presentations also highlight the growing interest in evaluating advanced lipid therapies in real-world patient populations with complex medical needs. Patients with severe hypertriglyceridemia frequently present with obesity, diabetes, liver disease, kidney dysfunction, and other metabolic complications that can influence treatment selection and tolerability.
Understanding how therapies perform in these populations is becoming increasingly important as precision medicine approaches expand within cardiometabolic disease management.
The company stated that the presentations from the EAS Congress will be made available both through the conference website and the investor relations section of Arrowhead’s corporate website.
As plozasiran development continues, the latest findings contribute to a growing body of evidence supporting APOC3-targeted RNA interference therapy as a potentially important approach for managing severe triglyceride disorders. The combination of durable triglyceride reduction, convenient dosing, and expanding safety characterization may position plozasiran as a significant addition to the evolving landscape of lipid management and rare metabolic disease therapeutics.
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, the Australian Therapeutic Goods Administration, and China’s National Medical Products Administration as an adjunct to diet to reduce triglycerides for adults with Familial Chylomicronemia Syndrome (FCS).
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.
For more information about REDEMPLO, visit Our Medicines.
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.
