Redemplo (plozasiran) / Arrowhead Pharmaceuticals, Sanofi - LARVOL DELTA

MUIR-3: Phase 3 Study of Plozasiran in Adults With Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=1456 | Completed | Sponsor: Arrowhead Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Dyslipidemia • Hypertriglyceridemia

Long Term Efficacy and Safety of Plozasiran in Patients with Familial Chylomicronemia Syndrome: 3-Year Data from the PALISADE Study and the Open-Label Extension (AHA 2026) - "Abstract is embargoed at this time."

Clinical • Familial Chylomicronemia Syndrome

Apolipoprotein C-III inhibition reduces acute pancreatitis in familial chylomicronemia syndrome: a meta-analysis of randomized trials (ESC 2026) - " PubMed, Embase, and Cochrane Library were systematically searched through December 2025 for randomized controlled trials enrolling patients with FCS treated with ApoC-III inhibitors (volanesorsen, olezarsen, plozasiran). In patients with FCS, ApoC-III inhibition produces profound and sustained triglyceride lowering and significantly reduces acute pancreatitis risk with an acceptable safety profile. These findings support ApoC-III–targeted therapy as a disease-modifying strategy in FCS, shifting management from dietary restriction alone toward effective pharmacologic prevention of recurrent pancreatitis."

Retrospective data • Cardiovascular • Dyslipidemia

Comparative efficacy of APOC3- and ANGPTL3-targeted therapies in severe hypertriglyceridemia: a systematic review and network meta-analysis (ESC 2026) - "Publication bias was evaluated through funnel plot analysis Results Olezarsen 80 mg, Olezarsen 50 mg, Plozasiran 10 mg, Plozasiran 25 mg, Plozasiran 50 mg, and Volanesorsen 300 mg were all significantly superior to placebo in reducing triglyceride levels (Figure 1). Conclusions This systematic review and network meta-analysis indicate Volanersorsen and higher doses of Olezarsen are most effective in reducing TG. Meanwhile, Olezarsen and Plozasiraan have greater effect in decreasing Acute Pancreatitis incidence, suggesting Olazarsen may be a preferable treatment for hypertriglyceridemia."

Retrospective data • Review • Cardiovascular • Dyslipidemia • ANGPTL3

Arrowhead intends to leverage data from the Phase 3 SHASTA-3, SHASTA-4 and MUIR-3 studies to seek marketing authorization for plozasiran in the broader sHTG population in multiple global geographies, beginning with a planned supplemental New Drug Application (sNDA) with the U.S. Food and Drug Administration (FDA) before the end of 2026 (Arrowhead Press Release)

FDA filing • Severe Hypertriglyceridemia

Arrowhead Pharmaceuticals Presents Phase 3 SHASTA-3 and SHASTA-4 Data Demonstrating Plozasiran Reduced Acute Pancreatitis Events in Patients with Severe Hypertriglyceridemia (Arrowhead Press Release) - "SHASTA-3 and SHASTA-4 met their primary and all prespecified secondary endpoints and demonstrated deep and durable reductions in triglycerides (TG), with median reductions from baseline of 79% and 81%, respectively at Month 12 (p<0.0001 in both studies). In a prespecified pooled analysis, plozasiran also significantly reduced acute pancreatitis (AP) events across the broad sHTG study population, with greater absolute benefit observed among patients at higher risk of AP. More than 90% of plozasiran-treated patients in both studies achieved TG levels below 500 mg/dL (<5.65 mmol/L) at Month 12, and more than half achieved TG levels below 150 mg/dL (<1.69 mmol/L)....Detailed results presented at the European Society of Cardiology (ESC) Congress 2026 in Munich as a Hot Line Late-Breaking Science session."

Late-breaking abstract • P3 data • Severe Hypertriglyceridemia

EFFECT OF PLOZASIRAN TARGETING APOC3 ON LIPOPROTEIN PARTICLE NUMBER AND SIZE MEASURED BY NMR IN PATIENTS WITH HYPERTRIGLYCERIDEMIA (HTG) - Christie M. Ballantyne (ACC 2025) - "PZN induces APOC3 decreases and favorable quantitative and qualitative changes in lipoproteins as assessed by NMR in HTG patients. PZN reduces TRL-P by ~50%, shifts LDL to larger particles, and increases HDL-P concentration. While high-potency TRL-lowering therapies can sometimes lead to an overall LDL-C increase, PZN does not increase LDL-P but does shift LDL particle size distribution from sdLDL towards larger sizes."

Clinical • Dyslipidemia • Hypertriglyceridemia • Mixed Hyperlipidemia • Severe Hypertriglyceridemia

Arrowhead Pharmaceuticals to Present New Clinical Data at the European Society of Cardiology Congress (Arrowhead Press Release) - "Detailed results from the Phase 3 SHASTA-3 and SHASTA-4 Studies of Plozasiran in Patients with Severe Hypertriglyceridemia will be presented as a HOT LINE Late-Breaking Science Session on August 30, 2026."

P3 data • Severe Hypertriglyceridemia

Plozasiran: a small interfering RNA therapy for hypertriglyceridemia and familial chylomicronemia syndrome. (PubMed, Daru) - "Ongoing phase 3 trials (SHASTA-3, SHASTA-4, SHASTA-5, SHASTA-10, MUIR-3 and CAPITAN) are further evaluating the efficacy and safety of plozasiran in broader populations with hypertriglyceridemia, including its potential role in reducing cardiovascular risk and preventing pancreatitis. Compared with earlier ApoC-III-targeted antisense oligonucleotides, plozasiran offers the advantages of less frequent dosing, sustained pharmacodynamic effects, and potentially a more favorable tolerability profile based on indirect evidence, positioning it as a promising therapeutic option for patients with FCS and other severe hypertriglyceridemia disorders inadequately managed with existing therapies."

Journal • Review • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Hypertriglyceridemia • Infectious Disease • Metabolic Disorders • Pain • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia

Arrowhead Pharmaceuticals...announced that people in Germany who live with a rare metabolic condition called Familial Chylomicronaemia Syndrome (FCS) are the among first in the European Union to have a new treatment option to reduce dangerously high levels of triglycerides (TGs, a type of fat) in their bloodstream (Businesswire) - "Following its marketing authorization by the European Commission in June 2026, REDEMPLO (plozasiran) is now listed in the Lauer-Taxe database and thus able to be prescribed, dispensed and reimbursed in Germany. REDEMPLO is authorized for use alongside diet, by adults diagnosed with FCS based on clinical symptoms or a genetic test, unlike other treatments that can be used only after genetic confirmation. It is taken as a subcutaneous injection once every three months."

Reimbursement • Familial Chylomicronemia Syndrome

Arrowhead Pharmaceuticals…announced that it has signed an agreement with an undisclosed third party to acquire a U.S. Food and Drug Administration (FDA) Rare Pediatric Disease Priority Review Voucher (PRV) (Businesswire) - "The company intends to utilize the PRV for its upcoming Supplemental New Drug Application (sNDA) submission for plozasiran, anticipated before the end of 2026, to seek approval to expand the approved indication to include patients with severe hypertriglyceridemia (sHTG)."

Licensing / partnership • Priority review • Severe Hypertriglyceridemia

Arrowhead Pharmaceuticals, Inc…announced topline results for the global Phase 3 SHASTA-3 and SHASTA-4 clinical studies of plozasiran in patients with severe hypertriglyceridemia (Businesswire) - "SHASTA-3 and SHASTA-4 successfully met the primary endpoint of triglyceride reduction versus placebo and met all prespecified secondary endpoints in both studies, including a statistically significant reduction in the rate of acute pancreatitis compared to placebo...In a pre-planned pooled analysis of AP events in SHASTA-3 and SHASTA-4, there was a statistically significant reduction in both the event rate (any individual patient with at least one AP event, p<0.0221), as well as the total incidence rate of AP events (p<0.0077) in plozasiran treated patients versus placebo...Detailed results from SHASTA-3 and SHASTA-4 will be presented as a HOT LINE Late Breaker at the European Society of Cardiology (ESC) Congress in Munich on August 30, 2026, and the company plans to host a conference call and webcast to discuss the results on August 31, 2026."

P3 data: top line • Severe Hypertriglyceridemia

Arrowhead intends to leverage the data from the Phase 3 SHASTA-3, SHASTA-4, and MUIR-3 studies to request marketing authorization for sHTG in multiple global geographies, beginning with a planned supplemental new drug application (sNDA) with the U.S. FDA before the end 2026. (Businesswire)

FDA filing • Severe Hypertriglyceridemia

Drugs for hypertriglyceridemia. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Dyslipidemia • Hypertriglyceridemia

Olezarsen and Plozasiran: Novel apoC-III targeting medications for the treatment of hypertriglyceridemia. (PubMed, J Cardiovasc Pharmacol) - "Overall, both agents appear generally well tolerated, although monitoring of liver enzymes and glycemic control is warranted for both agents, and additional monitoring of platelet counts for olezarsen. Future clinical trials are needed to assess whether the TG-lowering effects of each agent are associated with reduced risk of pancreatitis and ASCVD events."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hypertriglyceridemia • Pancreatitis

SHASTA-5: Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis (clinicaltrials.gov) - P3 | N=58 | Sponsor: Arrowhead Pharmaceuticals, Inc. / Sanofi (China) Investment Co., Ltd. / Ajinomoto Althea, Inc. | N=28 ➔ 58

Enrollment change • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

A Phase 3 Study of ARO-APOC3 / VSA001 / SAR449124 (Plozasiran) in Chinese Adults With Familial Chylomicronemia Syndrome (clinicaltrials.gov) - P3 | N=37 | Completed | Sponsor: Visirna Therapeutics HK Limited | Active, not recruiting ➔ Completed

Trial completion • Familial Chylomicronemia Syndrome

Arrowhead Pharmaceuticals Receives Marketing Authorization in the European Union for REDEMPLO (plozasiran) to Reduce Triglycerides in Adults with Familial Chylomicronemia Syndrome (FCS) (Businesswire) - "REDEMPLO is the first and only siRNA medicine authorized by the EC for adults with FCS, diagnosed either by the presence of clinical criteria or genetic testing....EC regulatory approval was supported by clinical data from the Phase 3 PALISADE study, a randomized, double-blind, placebo-controlled trial in 75 adults with clinically diagnosed or genetically confirmed FCS."

EMA approval • Familial Chylomicronemia Syndrome

Silencing Triglycerides: The Clinical Impact of Plozasiran and apoC-III Inhibition in Severe Hypertriglyceridemia. (PubMed, J Cardiovasc Pharmacol) - "While long-term cardiovascular outcome data remain pending, its ability to durably modulate APOC3 expression offers new hope for breaking the cycle of dyslipidemia-driven organ damage. As research progresses, this therapy may redefine standards of care for high-risk populations, bridging a critical gap in preventive cardiology and pancreatology."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Metabolic Disorders • Pancreatitis • Severe Hypertriglyceridemia • APOB • APOC3 • LPL

"The Canadian Drug Expert Committee (CDEC) recommends that plozasiran be reimbursed as an adjunct to diet to reduce TG levels for adult patients with FCS for whom standard TG-lowering therapies have been inadequate, only if the conditions listed in…are met” (Ottawa (ON): Canadian Agency for Drugs and Technologies in Health)

Reimbursement • Hypertriglyceridemia • Metabolic Disorders

Clinical Pharmacology of Plozasiran. (PubMed, Am J Cardiovasc Drugs) - "A pathway involving small interfering RNA that selectively inhibits apolipoprotein C-III (APOC3) messenger RNA through RNA interference is currently being studied to reduce levels of apoC-III and thus, triglycerides. This review presents and discusses the current pharmacokinetic, pharmacodynamics, and clinical and scientific evidence pertaining to plozasiran, a small interfering RNA medicine."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • APOC3

Efficacy and Safety of RNA Interference Therapy with Plozasiran for Familial Chylomicronemia Syndrome: A Systematic Review and Meta-Analysis (ENDO 2026) - "Proxy quality-of-life outcomes indicated a moderate-to-large improvement (SMD +0.65, 95% CI +0.60 to +0.70). Conclusion Plozasiran demonstrated large and durable triglyceride and ApoC-III reductions with a favorable safety profile, and the overall risk of bias across included studies was low."

Retrospective data • Review • Dyslipidemia • Familial Chylomicronemia Syndrome • Genetic Disorders • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • Thrombocytopenia

Triglyceride Lowering Treatment with Apolipoprotein C3 Inhibitors and Pancreatitis: A Meta-Analysis of Randomized Trials (ENDO 2026) - " 13 placebo controlled randomized trials evaluating ApoC-3 inhibitors (Olezarsen, Plozasiran, Volanesorsen) in patients with either primary or secondary hypertriglyceridemia were included (inception-December 2025). ApoC-3 inhibitors significantly reduced TGs levels and risk of pancreatitis."

Retrospective data • Dyslipidemia • Hematological Disorders • Hypertriglyceridemia • Pancreatitis • Thrombocytopenia • APOC3

Management of Recurrent Hypertriglyceridemia-Induced Acute Pancreatitis (ENDO 2026) - "She had discontinued fenofibrate after her 2021 admission and denied alcohol or gallstone as well as thyroid and kidney problem history. 12 Emerging agents targeting apolipoprotein C-III, such as plozasiran, may prevent recurrence in high-risk patients. 13Further studies are needed to establish the insulin therapy without complications in non-diabetic hypertriglyceridemia-induced acute pancreatitis."

Dyslipidemia • Gastroenterology • Hypertriglyceridemia • Hypoglycemia • Pancreatitis • Severe Hypertriglyceridemia • LPL

Use of plozasiran across a spectrum of hypertriglyceridemia: Long-term efficacy and safety data from the open-label extension period of SHASTA-2 and MUIR Trials. (PubMed, Am J Prev Cardiol) - P2 | "Long-term open-label treatment with plozasiran resulted in sustained TG reductions compared to baseline, across a broad range of HTG, with a safety profile consistent with earlier trials. (Funded by Arrowhead Pharmaceuticals, Inc.; ClinicalTrials.gov number NCT05413135)."

Clinical • Journal • Back Pain • Diabetes • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Infectious Disease • Metabolic Disorders • Mixed Hyperlipidemia • Musculoskeletal Pain • Novel Coronavirus Disease • Pain • Respiratory Diseases • Severe Hypertriglyceridemia • APOB