Redemplo (plozasiran) / Arrowhead, Sanofi - LARVOL DELTA

Clinical considerations for the treatment of patients with familial chylomicronemia syndrome using a hepatic-targeted APOC3 antisense oligonucleotide. (PubMed, Am J Prev Cardiol) - "Olezarsen, a hepatic-targeted APOC3 antisense oligonucleotide, is the first US Food and Drug Administration-approved therapy specifically for FCS treatment, indicated as an adjunct to diet to reduce triglycerides in adult patients with FCS; olezarsen is also European Medicines Agency-approved. Plozasiran, a small interfering RNA therapy targeting APOC3, is in late-stage clinical development. This article describes the updated diagnosis and clinical management of FCS and practical considerations for APOC3-targeting treatment."

Journal • Review • Dyslipidemia • Familial Chylomicronemia Syndrome • Fatigue • Genetic Disorders • Hypertriglyceridemia • Pain • Pancreatitis

Arrowhead Pharmaceuticals Reports 2025 Fiscal Year-End Results (Businesswire) - "Announced the One-REDEMPLO pricing model that creates one consistent price across current and potential future indications; Launched Rely On REDEMPLO, a patient support program providing support services and resources for patients at each stage of the treatment journey with REDEMPLO, including financial assistance options for eligible patients."

Commercial • Familial Chylomicronemia Syndrome

Arrowhead Pharmaceuticals Receives FDA Breakthrough Therapy Designation for Plozasiran in Severe Hypertriglyceridemia (Businesswire) - "Arrowhead is on schedule to complete the SHASTA-3, SHASTA-4, and MUIR-3 Phase 3 clinical studies of plozasiran in mid-2026 and intends to submit a supplemental New Drug Application (sNDA) to the FDA by year-end 2026. Arrowhead also plans to seek regulatory approval with additional global regulatory authorities thereafter."

Breakthrough therapy • FDA filing • Trial completion date • Hypertriglyceridemia • Severe Hypertriglyceridemia

Arrowhead Pharmaceuticals to Participate in Upcoming December 2025 Conferences (Businesswire) - "Arrowhead Pharmaceuticals, Inc...announced that it is scheduled to participate in the following upcoming events: Piper Sandler 37th Annual Healthcare Conference – December 2-4, 2025; 8th Annual Evercore Healthcare Conference – December 2-4, 2025; World Congress of Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC) – December 4-6, 2025."

Clinical data • Familial Chylomicronemia Syndrome • Pancreatitis • Severe Hypertriglyceridemia

Course of Pregnancy in a Woman With Familial Chylomicronemia Syndrome Treated With Plozasiran, a Small Interfering RNA Against ApoC3. (PubMed, JIMD Rep) - "This case suggests that plozasiran might be safe for the mother and the fetus and could prevent incremental pregnancy-driven TG elevation and occurrence of AP in women with sHTG. This is consistent with the long duration of action and hepatic half-life of plozasiran in clinical studies where TG levels remained sustainably lower than baseline > 9 months after the last injection."

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

Arrowhead Pharmaceuticals Announces FDA Approval of REDEMPLO (plozasiran) to Reduce Triglycerides in Adults with Familial Chylomicronemia Syndrome (FCS) (Businesswire) - "The FDA approval was supported by clinical data from the Phase 3 PALISADE study, a randomized, double-blind, placebo-controlled trial in adults with clinically diagnosed or genetically confirmed FCS....REDEMPLO will be available in the U.S. before the end of the year."

FDA approval • Launch US • Familial Chylomicronemia Syndrome

SHASTA-5: Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis (clinicaltrials.gov) - P3 | N=288 | Recruiting | Sponsor: Arrowhead Pharmaceuticals | N=140 ➔ 288

Enrollment change • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

The Efficacy and Safety of Plozasiran on Lipid Profile in Dyslipidemic Disorders: A Systematic Review and Meta-Analysis. (PubMed, Cardiovasc Drugs Ther) - "While Plozasiran shows strong potential as a therapeutic option for severe dyslipidemic conditions, further studies are needed to compare its efficacy and safety with currently available treatments and, more importantly, evaluate its impact on clinical outcomes for implementation in clinical practice."

Journal • Retrospective data • Review • Metabolic Disorders • Pain • APOB

The Efficacy and Safety of Plozasiran on Lipid Profile in Dyslipidemic Disorders: A Systematic Review and Meta-Analysis (AHA 2025) - "For ApoB, only the 25 mg and 50 mg quarterly regimens significantly reduced its levels study completion. Regarding safety, patients receiving plozasiran experienced a higher incidence of any adverse events (RR = 1.11, 95% CI [1.03, 1.19], P < 0.01), headache (RR = 1.85, 95% CI [1.14, 3.02], P = 0.01), and mild rises in HbA1C levels (MD = 0.19, 95% CI [0.06, 0.31], P < 0.01).ConclusionWhile Plozasiran shows strong potential as a therapeutic option for severe dyslipidemic conditions, further studies are needed to compare its efficacy and safety with currently available treatments and, more importantly, evaluate its impact on clinical outcomes for implementation in clinical practice."

Retrospective data • Review • Cardiovascular • Dyslipidemia • Metabolic Disorders • Pancreatitis • APOB

An Updated Review of Novel Triglyceride-Lowering Therapies in Adults with Familial Chylomicronemia Syndrome. (PubMed, Am J Cardiovasc Drugs) - "A literature search in PubMed and EMBASE was conducted from January 2013 to July 2025 using keywords "familial chylomicronemia syndrome", "olezarsen", "volanesorsen", and "plozasiran". These new apoC-III lowering medications provide a novel treatment approach for patients with FCS, a population long without effective pharmacological treatment options. Provider familiarity with the availability and purpose of these medications will allow patients to receive the best therapy available to manage FCS."

Journal • Review • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis

Lessons from recent clinical trials for the prevention of acute pancreatitis in chylomicronemia syndromes. (PubMed, Curr Opin Endocrinol Diabetes Obes) - "These emerging mechanism-based therapies are reshaping the management of severe hypertriglyceridemia, offering targeted approaches to reduce triglycerides and acute pancreatitis risk. Ongoing studies will clarify long-term safety, durability of response, and optimal patient selection, providing a framework for improved clinical outcomes."

Journal • Dyslipidemia • Hepatology • Hypertriglyceridemia • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Pancreatitis • Severe Hypertriglyceridemia • ANGPTL3 • FGF21 • LPL

Sanofi has brought to the China International Import Expo two new cardiovascular therapies through partnerships with Chinese partners, highlighting the French pharmaceutical giant's local strategy focused on partnership-driven innovation. (Yicai Global) - "The global debuts of aficamten for hypertrophic cardiomyopathy and plozasiran for familial chylomicronemia syndrome and severe hypertriglyceridemia address critical gaps in China's cardiovascular disease treatment landscape."

Commercial • Cardiomyopathy • Familial Chylomicronemia Syndrome

Anti-apoC-III Therapies and Implications for Treatment of Pancreatitis and Cardiovascular Disease. (PubMed, Curr Atheroscler Rep) - "APOC3 inhibition is now an established therapeutic approach for reducing the risk of acute pancreatitis in FCS, with three agents, volanesorsen, olezarsen, and plozasiran, demonstrating efficacy. However, its role in ASCVD prevention remains unproven. This review evaluates current APOC3 - targeted therapies for FCS, including available comparative data, and synthesizes the emerging literature on the potential of APOC3 inhibition to reduce the burden of acute pancreatitis in broader populations with severe hypertriglyceridemia, as well as its potential role in ASCVD risk reduction."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia • LPL

Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia. (PubMed, Nucleic Acids Res) - "APOC3 mRNA, primarily synthesized by hepatocytes, is an ideal target for GalNAc-conjugated RNA-targeted therapies such as the antisense oligonucleotide (ASO) oleszarsen and small-interference RNA (siRNA) plozasiran. Additionally, selectivity and tolerability assessments in human cells, rodents, and nonhuman primates showed excellent safety and tolerability. A comparative analysis of the lead APOC3 siRNA with a surrogate of a clinical-stage APOC3 siRNA drug suggests the potential for similar or better potency and efficacy combined with less frequent dosing, potentially reducing the treatment burden on patients with hypertriglyceridemia."

Journal • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Hypertriglyceridemia • Pancreatitis

Safety, pharmacokinetics and pharmacodynamics of Plozasiran in Chinese healthy volunteers. (PubMed, Cardiovasc Diabetol) - "Plozasiran at 25 and 50 mg was well tolerated with acceptable safety profile in Chinese HVs. Safety, PK and PD profiles observed in the present study were consistent with the data reported from clinical studies conducted outside China."

Biomarker • Clinical • Journal • PK/PD data • Dyslipidemia • Hypertriglyceridemia • APOB

SHASTA-5: Study of Plozasiran in Adults With Severe Hypertriglyceridemia at Risk of Acute Pancreatitis (clinicaltrials.gov) - P3 | N=140 | Recruiting | Sponsor: Arrowhead Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial primary completion date: Mar 2028 ➔ Mar 2029

Enrollment open • Trial primary completion date • Dyslipidemia • Hypertriglyceridemia • Pancreatitis • Severe Hypertriglyceridemia

A randomized, placebo-controlled phase 3 study of plozasiran in patients with familial chylomicronemia syndrome: PALISADE - 1 year open label extension (ESC-WCC 2025) - "Deep and durable reductions in circulating ApoC3 and TG levels seen in the blinded phase of the study have continued during the first 12 months of the OLE. Plozasiran appears to be a promising new therapy to lower severely elevated plasma TG in patients suffering from FCS."

Clinical • P3 data • Cardiovascular • Dyslipidemia • APOB • APOC3 • LPL

Arrowhead Pharmaceuticals to Participate in Upcoming September 2025 Conferences (Businesswire)

Clinical data • Familial Chylomicronemia Syndrome • Mixed Hyperlipidemia

SHASTA-3: Study of Plozasiran (ARO-APOC3) in Adults With Severe Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=446 | Active, not recruiting | Sponsor: Arrowhead Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

Arrowhead Pharmaceuticals Reports Fiscal 2025 Third Quarter Results (Businesswire) - "Selected Recent Events:...Completed enrollment in investigational plozasiran clinical studies SHASTA-3, SHASTA-4, and MUIR-3, the company’s global Phase 3 clinical studies designed to support regulatory submissions for marketing approval in the treatment of severe hypertriglyceridemia. Arrowhead anticipates completing the primary portion of these studies in mid-2026 with topline data expected shortly thereafter and planned submissions for regulatory review and potential approval to follow."

P3 data: top line • Trial status • Severe Hypertriglyceridemia

SHASTA-10: Long-Term Safety and Efficacy of Plozasiran in Adults With Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=840 | Recruiting | Sponsor: Arrowhead Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Hypertriglyceridemia • APOB

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

Enrollment closed • Dyslipidemia • Hypertriglyceridemia

SHASTA-4: Study of Plozasiran in Adults With Severe Hypertriglyceridemia (clinicaltrials.gov) - P3 | N=311 | Active, not recruiting | Sponsor: Arrowhead Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

Arrowhead Subsidiary Visirna Sells Rights to Hypertriglyceridemia Candidate Plozasiran in Greater China to Sanofi (Businesswire) - "Arrowhead Pharmaceuticals, Inc...announced the signing of an asset purchase agreement between Sanofi and Visirna Therapeutics, a majority-owned subsidiary of Arrowhead created to develop and commercialize four of Arrowhead’s investigational cardiometabolic candidates in Greater China. Under the terms, Sanofi will acquire rights to develop and commercialize investigational plozasiran, Arrowhead’s first-in-class RNA interference (RNAi) therapeutic candidate designed to reduce production of apolipoprotein C-III (APOC3) as a potential treatment for familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG), in Greater China."

Commercial • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Severe Hypertriglyceridemia

ApoC-III as Therapeutic Target: Is it Primetime for Clinical Use? (PubMed, Curr Atheroscler Rep) - "Current treatments targeting Apo C-III include two antisense oligonucleotides (ASOs) (volanesorsen and olezarsen), and a small interfering RNA (siRNA) (plozasiran). ApoC-III inhibition represents an innovative and effective approach in managing hypertriglyceridaemia and its complications. Further outcome-driven trials are essential to define its role in cardiovascular risk reduction."

Journal • Review • Cardiovascular • Dyslipidemia • Familial Chylomicronemia Syndrome • Hematological Disorders • Pancreatitis • Thrombocytopenia • LPL