Wainua (eplontersen) / Ionis, AstraZeneca - LARVOL DELTA

AN EARLY HARBINGER OF TRANSTHYRETIN CARDIAC AMYLOIDOSIS: A CASE SERIES ON ATRIAL AMYLOID (ACC 2026) - "On Acoramidis and Eplontersen (given neurologic symptoms). Early recognition of atrial involvement may facilitate timely diagnosis and intervention before overt ventricular disease develops."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Coronary Artery Disease • Musculoskeletal Pain

Therapeutic Efficacy and Safety Profile of Eplontersen in Hereditary Transthyretin-Mediated Amyloidosis: A Systematic Review. (PubMed, Health Sci Rep) - "Future research is needed on long-term safety, early diagnosis, personalized treatments, and combination therapies. This drug emphasizes the importance of continued research for optimal patient care and outcomes."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Pain

Efficacy of Eplontersen According to Baseline Polyneuropathy Severity in Patients with Hereditary Transthyretin Amyloidosis: A Subgroup Analysis of the NEURO-TTRansform Index Study (AAN 2026) - P3 | "Consistent benefits of eplontersen treatment in the degree of neuropathy impairment and in QoL were observed to Week 66, regardless of baseline PN severity."

Clinical • Amyloidosis • Cardiac Amyloidosis • Diabetic Neuropathy • Pain

Diagnostic Patterns and Clinical Characteristics of Hereditary ATTR Amyloidosis: A Retrospective Study From a U.S. Health System (AAN 2026) - "As gene-silencing therapies such as vutrisiran, and eplontersen become more widely available, characterizing diagnostic and treatment patterns is critical.Design/ We conducted a five-year retrospective review across the MedStar Health system...Tafamidis alone was prescribed in 43%, tafamidis plus siRNA agents in 13%, tafamidis plus eplontersen in 6%, siRNA alone in 5%, and ASO alone in 2%... In this diverse, urban cohort, V142I was predominant. Many patients lacked full diagnostic workup or treatment, underscoring disparities in care. These findings are especially relevant given the expanding role of gene-silencing therapies in hATTR management."

Retrospective data • Amyloidosis • Cardiovascular • CNS Disorders

Extracardiac Disease and Targeted Therapies in Heart Transplant Recipients with Transthyretin Cardiac Amyloidosis (ISHLT 2026) - "Vutrisiran (55%) was the predominant silencer used followed by eplontersen (9%). While ATTR-targeted therapies are critical for the management of systemic disease, their use post-HTx was variable. These findings highlight the need for structured post-transplant strategies to ensure ongoing management of ECD in ATTR patients."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Musculoskeletal Pain • Transplantation

WAINUA (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated sales of $69 million and $212 million resulting in royalty revenue of $16 million and $49 million in the fourth quarter and the year ended December 31, 2025, respectively (Businesswire)

Sales • Amyloidosis

ION-682884 in Patients With TTR Amyloid Cardiomyopathy (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Brigham and Women's Hospital | N=17 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure

Precision medicine with pioneering RNAi therapeutics in ATTR amyloidosis: from bench to bedside. (PubMed, Eur J Intern Med) - "Major clinical trials evaluating first- and second-generation RNA-targeted agents-including patisiran, vutrisiran, inotersen, and eplontersen-are summarized, highlighting efficacy, safety profiles, dosing regimens, and relevance across different ATTR phenotypes. As RNA-based therapies continue to evolve, integration of molecular insights with clinical phenotyping and real-world evidence will be essential to fully realize the potential of precision medicine for patients with ATTR amyloidosis."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Developmental Disorders • Pain

EPPRO: The Eplontersen Pregnancy and Lactation Outcomes Study (clinicaltrials.gov) - P=N/A | N=10 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Amyloidosis • Cardiac Amyloidosis

Small RNA or oligonucleotide drugs and challenges in evaluating drug-drug interactions. (PubMed, Front Pharmacol) - "Widespread adoption of these strategies has further enabled the application of oligonucleotides as viable drugs and expanded the class of RNA therapeutics, with thirteen antisense oligonucleotides (ASOs) (fomiversen, mipomersen, nusinersen, inotersen, eteplirsen, golodirsen, casimersen, viltolarsen, tofersen, eplontersen, olezarsen, and donidalorsen), seven small interfering RNAs (siRNAs) (patisiran, givosiran, lumasiran, inclisiran, vutrisiran, nedosiran, and fitusiran), and two aptamers (pegaptanib and avacincaptad pegol) that have been approved by the United States Food and Drug Administration (FDA). This article provides an overview of FDA-approved oligonucleotide therapies, emphasizing chemical modifications, molecular targets for mechanistic actions, and available ADME and PK/PD properties, followed by the discussion of critical needs for risk assessment strategies suited for this unique modality that focuses on possible DDIs with concomitant drugs. The latter may..."

Journal • Review

Anti-PF4 antibodies are a potential mediator of antisense oligonucleotide (ASO)-induced thrombocytopenia. (ASH 2025) - "Twelve ASOs, Inotersen, Eplontersen,Olezarsen, Fomivirsen, Mipomersen, Tofersen, Nusinersen, Eteplirsen, Golodirsen, Viltolarsen,Casimersen (all FDA approved) and Volanesorsen (EMA approved) were evaluated in this study. With two ASOs, Fomivirsen and Eteplirsen, direct activation of platelets was noted. Studieswith additional ASOs revealed a novel immune mechanism involving ASO-PF4 complex formation andanti-PF4 antibody recognition that can plausibly mediate ASO-induced thrombocytopenia. These findingshighlight the key role PS linkages may play in ASO immunogenicity and provide a mechanistic frameworkfor risk mitigation in ASO drug design, supporting the safer development and broader application of ASOtherapeutics."

Hematological Disorders • Thrombocytopenia

RNA Interference Therapeutics for Hereditary Transthyretin-Mediated Amyloidosis with Neuropathy: A Systematic Review (ASH 2024) - "Currently, limited treatment options are available for ATTRv, which include orthotopic liver transplantation and transthyretin tetramer stabilizers (tafamidis or diflunisal)...The most common cause of death reported was cardiac failure.Conclusion : RNA interference therapies, including Eplontersen, Inotersen, Vutrisiran, and Patisiran, have demonstrated significant benefits in enhancing the quality of life for patients with ATTRv and associated polyneuropathy...While RNAi therapies offer substantial symptomatic relief, vigilant surveillance for side effects is crucial to optimize patient outcomes and ensure safety. Further studies, including comparative studies, are essential to establish therapeutic protocols and ensure improved quality of life for patients with ATTRv."

Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Diabetic Neuropathy • Glomerulonephritis • Heart Failure • Hematological Disorders • Lupus Nephritis • Nephrology • Pain • Renal Disease • Thrombocytopenia

Neurological efficacy and safety of RNA therapeutics in hereditary transthyretin amyloidosis: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Ther Adv Cardiovasc Dis) - "RNA therapeutics are effective and well-tolerated in patients with hATTR, significantly improving quality of life and the progression of neurological impairment. siRNAs demonstrate better outcomes compared to ASOs."

Journal • Retrospective data • Review • Amyloidosis • Cardiac Amyloidosis • Diabetic Neuropathy • Gastrointestinal Disorder • Pain

Association of TTR-Targeted Therapies with Cardiovascular Outcomes in Transthyretin Amyloid Cardiomyopathy: A Real-World Analysis (AHA 2025) - "Adults with a diagnosis of ATTR-CM were categorized into three groups based on prescription records: TTR stabilizers (e.g., tafamidis, acoramidis), TTR gene silencers (e.g., vutrisiran, eplontersen, patisiran, inotersen), or standard medical therapy. In this large, real-world analysis of patients with ATTR-CM, use of TTR stabilizers was associated with a lower incidence of major cardiovascular events compared with standard care. TTR gene silencers showed a similar directional association, though limited by a smaller sample size. These findings support further investigation in prospective studies to better understand the relationship between TTR-targeted therapies and clinical outcomes."

Clinical • Real-world • Real-world evidence • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Ventricular Tachycardia

Gastric Transthyretin Amyloidosis: A Unique Case of Gastric Outlet Obstruction and Gastroparesis (ACG 2025) - "After the EGD, her symptoms initially improved, and on discharge, she continued Tafamidis and Eplontersen. Moreover, a gastric simulator is used as a last resort for patients with gastric ATTR complicated with gastroparesis who haven't responded to other treatments. Due to the rare co-occurring complications and underreported incidence, we aim to raise awareness and strongly advocate for the need for large, multi-center, prospective studies to capture the impact of gastric ATTR and its burden on the US healthcare system."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Gastrointestinal Disorder • Infectious Disease • Metabolic Disorders

Neuropathy impairment and nutritional status with eplontersen in patients with hereditary transthyretin-mediated amyloidosis. (PubMed, Amyloid) - No abstract available

Journal • Amyloidosis • Pain

Recent Highlights – Partnered Medicines (Businesswire) - "WAINUA (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated sales of $59 million and $143 million resulting in royalty revenue of $13 million and $33 million in the third quarter and the nine months ended September 30, 2025, respectively."

Sales • Amyloidosis

Cardiac Amyloidosis: Tribulations and New Frontiers. (PubMed, J Pers Med) - "Critically, it is imperative that physicians develop close relationships with the patient that addresses not only their individual health needs but also their unique psychosocial situation. Therefore, more clinical trials, protocols and patient resources are needed to better inform and guide providers managing these complex patient needs."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Transplantation

Data from the CARDIO-TTRansform study of eplontersen for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) are expected in H2 (Ionis Pharmaceuticals Press Release)

P3 data • Amyloidosis • Cardiomyopathy

EPPRO: The Eplontersen Pregnancy and Lactation Outcomes Study (clinicaltrials.gov) - P=N/A | N=10 | Not yet recruiting | Sponsor: AstraZeneca

New trial • Amyloidosis • Cardiac Amyloidosis

Atrial structure and function in patients with amyloidosis: findings from the NEURO-TTRansform study. (ESC-WCC 2025) - " Patients enrolled in the NEURO-TTRansform study, an open label study with historical control, randomized to eplontersen vs inotersen, then cross over from inotersen to eplontersen of adult patients with Coutinho Stage 1 OR 2 disease, were studied... In a population of patients with amyloid polyneuropathy, abnormalities of LA strain were highly prevalent, even in patients without known cardiac involvement. This suggests LA strain can be used as a marker of early amyloid cardiac disease and should be looked for in patients with known genetic variants.Figure: A. Number of strain abnormalities by Cardiac Status. B."

Clinical • Atherosclerosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Heart Failure

A review of Eplontersen use in hereditary transthyretin amyloidosis. (PubMed, Neurodegener Dis Manag) - "Eplontersen is suitable for long term use in patients with disease related polyneuropathy and is currently being studied for use in patients with cardiomyopathy. In this review, we discuss the clinical efficacy, mechanism of action, pharmacology, tolerability, and social determinants of health affecting the use of Eplontersen."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Pain

Transthyretin Amyloid Cardiomyopathy-2025 Update: Current Diagnostic Approaches and Emerging Therapeutic Options. (PubMed, J Clin Med) - "First-generation therapies such as tafamidis have demonstrated survival benefits in ATTR-CM. More recently, second-generation agents-such as the TTR stabilizer acoramidis and RNA silencers including vutrisiran and eplontersen-have shown promising efficacy in clinical trials...This review outlines current diagnostic strategies and therapeutic options for ATTR amyloidosis, emphasizing the need for early detection and individualized treatment approaches. The expanding therapeutic landscape highlights the importance of accurate phenotyping and timely intervention to optimize clinical outcomes."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Pain

An Extension Study to Assess Long-Term Safety of Eplontersen in Adults With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM) (clinicaltrials.gov) - P3 | N=1400 | Enrolling by invitation | Sponsor: Ionis Pharmaceuticals, Inc. | Recruiting ➔ Enrolling by invitation | Trial primary completion date: Apr 2029 ➔ Aug 2029

Enrollment status • Trial primary completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: Where We Are and Where We Are Going. (PubMed, J Clin Med) - "TTR stabilizers, such as tafamidis and acoramidis, can reduce TTR instability and subsequent amyloid fibril formation...Gene-silencing therapies using small interfering RNAs (siRNAs), such as patisiran and vutrisiran, or antisense oligonucleotide inhibitors (ASOs), such as inotersen and eplontersen, serve as powerful therapeutic options by decreasing TTR production; trials on patients with ATTR-CM have been recently published or are ongoing. Novel, emerging therapies aim to enhance fibril clearance using monoclonal antibodies, such as NI006, that target amyloid deposits in the myocardium, promoting their depletion, plausibly with regression of the structural and functional impairments caused by the disease...Future directions will involve improving patients' screening to achieve earlier diagnoses, optimising patients' selection for disease-modifying therapy and identifying criteria for the treatment's response or lack thereof to possibly consider therapy..."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure