Wainua (eplontersen) / Ionis, AstraZeneca - LARVOL DELTA

Long-Term Impact of Eplontersen on Technetium-99m-Pyrophosphate Single-Photon Emission Computed Tomography/Computed Tomography in Ala97Ser Hereditary Transthyretin Amyloid Cardiomyopathy. (PubMed, Acta Cardiol Sin) - "A further reduction between the first and second follow-up was also noted (2.94 ± 0.38 to 2.86 ± 0.39, p = 0.025). Serial 99mTc-PYP SPECT/CT imaging demonstrated a significant reduction in myocardial tracer uptake over a mean follow-up of 37.5 months in patients with hATTR-CM undergoing eplontersen therapy."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Eplontersen with and without background transthyretin stabilizers in transthyretin amyloid cardiomyopathy: secondary analysis of a phase 3, randomized controlled trial. (PubMed, Nat Med) - P3 | "These findings of a strong treatment effect modification may offer insight for therapeutic decision-making in clinical practice. ClinicalTrials.gov registration: NCT04136171."

Journal • P3 data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

sTTRing: Long-term Safety of Eplontersen Treated aTTR Patients and in Liver Transplant and Severely Hepatic Impaired Subpopulations (clinicaltrials.gov) - P=N/A | N=320 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Hepatology • Transplantation

The CARDIO-TTRansform Scintigraphy Sub-study (clinicaltrials.gov) - P=N/A | N=163 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial. (PubMed, J Peripher Nerv Syst) - P3 | "Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum."

Journal • Amyloidosis • Cardiac Amyloidosis • CNS Disorders • Diabetic Neuropathy • Pain

Efficacy and safety of transthyretin gene silencer eplontersen in patients with transthyretin amyloid cardiomyopathy receiving stabiliser therapy in the CARDIO-TTRansform trial (ESC 2026) - No abstract available

Clinical • Late-breaking abstract • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

CARDIO-TTRansform: efficacy and safety of eplontersen in patients with transthyretin amyloid cardiomyopathy (ESC 2026) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Eplontersen for Transthyretin Amyloid Cardiomyopathy. (PubMed, N Engl J Med) - P3 | "Among patients with ATTR-CM, eplontersen therapy did not lead to a lower risk of a composite of death from cardiovascular causes and recurrent cardiovascular events than placebo up to 140 weeks. (Funded by Ionis Pharmaceuticals and AstraZeneca; CARDIO-TTRansform ClinicalTrials.gov number, NCT04136171.)."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

ATTR-CM: CARDIO-TTRansform: A Study to Evaluate the Efficacy and Safety of Eplontersen (Formerly Known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR CM) (clinicaltrials.gov) - P3 | N=1438 | Completed | Sponsor: Ionis Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Clinical Pharmacology of Eplontersen, the First Approved GalNAc-Conjugated Antisense Oligonucleotide. (PubMed, J Clin Pharmacol) - "These findings support that 45 mg Q4W is appropriate for patients with ATTRv-PN without the need for dose modification. In vitro and model-based analyses indicate low potential for clinically relevant plasma protein binding displacement and CYP- or transporter-mediated drug-drug interactions, and demonstrate no clinically meaningful effects on the QT prolongation and a predominantly non-neutralizing anti-drug antibody profile without impact on efficacy or safety."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Pain

Disease modifying treatment of hereditary transthyretin amyloidosis with polyneuropathy in Germany - expert consensus of the German society of amyloid diseases (DGAK) and the German neurological society (DGN). (PubMed, Neurol Res Pract) - "For first-line treatment, the DGAK/DGN recommends one of the two second-generation TTR gene-silencing agents, vutrisiran or eplontersen, for most patients with symptomatic ATTRv-PN. Aligned with that, there are no observed or expected CNS side effects of any of the DMTs. In the future, next-generation RNA-interference therapies, gene-editing approaches, and amyloid-depleting antibodies are expected to further expand therapeutic options."

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

Disease-Modifying Therapies for Transthyretin Amyloid Cardiomyopathy: Current Evidence and Emerging Strategies. (PubMed, J Clin Med Res) - "This narrative review synthesizes current evidence on pharmacologic strategies for ATTR-CM, including transthyretin stabilizers such as tafamidis and acoramidis, gene-silencing therapies including patisiran, vutrisiran, and eplontersen, fibril disruptors, and emerging amyloid-depleting monoclonal antibodies and gene-editing approaches. The convergence of early diagnosis through improved imaging and biomarker strategies with targeted therapeutics has substantially changed the outlook for patients with a previously untreatable disease. Future directions emphasize combination therapies, biomarker-guided treatment selection, and precision medicine approaches tailored to disease genotype and phenotype."

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

Disease-Modifying Therapies for Hereditary Transthyretin Amyloidosis with Polyneuropathy: Current Status and Future Perspectives. (PubMed, Neurol Ther) - "These therapies include TTR stabilizers, such as tafamidis, diflunisal, and acoramidis, as well as RNA-silencing agents, such as patisiran, vutrisiran, inotersen, and eplontersen, which reduce hepatic production of TTR and slow disease progression...Emerging gene-editing approaches, including CRISPR-based therapies like NTLA-2001, may provide a one-time treatment and long-term disease control, representing a promising future direction for managing ATTRv-PN...These include high treatment costs, limited global accessibility, uncertainty regarding optimal treatment selection and sequencing, and the need for long-term real-world, patient-centered outcome data. This review summarizes current disease-modifying therapies for ATTRv-PN, compares their mechanisms and clinical evidence, and discusses unmet needs and future research directions, with the aim of providing a practical and comprehensive overview for clinicians treating patients with ATTRv-PN."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Developmental Disorders • Gene Therapies • Pain • Transplantation

ATTRiumph: A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM (clinicaltrials.gov) - P2 | N=326 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Guidelines for the management of hereditary ATTR amyloidosis 2026. (PubMed, Amyloid) - "Tafamidis and vutrisiran are indicated for both polyneuropathy (ATTRv-PN) and cardiomyopathy (ATTR-CM), patisiran, eplontersen and diflunisal are for ATTRv-PN only, and acoramidis is for ATTR-CM only. The currently available disease-modifying therapeutics have a limited effect on central nervous system (CNS) and ocular manifestations since they target either blood circulating TTR from the liver or ATTR amyloid fibrils misfolding in the blood and depositing in systemic (non-CNS, non-ocular) tissues. Development of disease-modifying therapies for CNS and ocular ATTR amyloidosis is an urgent unmet medical need."

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

Gene silencing versus protein stabilization in transthyretin amyloid cardiomyopathy: contextualizing the HELIOS-B results and the road to precision agent selection. (PubMed, Ann Med Surg (Lond)) - "Transthyretin amyloid cardiomyopathy (ATTR-CM) now has three approved disease-modifying agents: tafamidis, acoramidis, and vutrisiran, representing two mechanistically distinct classes: TTR tetramer stabilizers and RNA interference (RNAi) gene silencers. The ongoing CARDIO-TTRansform trial of the antisense oligonucleotide eplontersen will provide further comparative data, but head-to-head evidence across existing approved agents is absent. The question of how to sequence or select between mechanistically distinct agents for individual patients represents the central unresolved issue in ATTR-CM management."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Ionis Pharmaceuticals, Inc…announced that the CARDIO-TTRansform Phase 3 trial for eplontersen in patients with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) did not meet the primary efficacy endpoint of the composite outcome of cardiovascular (CV) mortality and recurrent CV clinical events up to Week 140 compared with placebo. (Ionis Pharmaceuticals Press Release) - "In a prespecified subgroup analysis of patients treated with eplontersen monotherapy compared to placebo, a nominally significant hazard ratio of 0.71 was observed on the composite outcome of CV mortality and recurrent CV events. In patients who were on stabilizer therapy at baseline, no treatment effect was observed. In the overall population, multiple secondary, imaging and biomarker analyses favored eplontersen versus placebo...Ionis and AstraZeneca will continue to analyze the full data set, and results will be shared with the scientific community at the European Society of Cardiology (ESC) Congress in August 2026."

P3 data • Cardiac Amyloidosis • Cardiomyopathy

sTTRing: Long-term Safety of Eplontersen Treated aTTR Patients and in Liver Transplant and Severely Hepatic Impaired Subpopulations (clinicaltrials.gov) - P=N/A | N=320 | Not yet recruiting | Sponsor: AstraZeneca

New trial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Hepatology • Transplantation

ATTRiumph: A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM (clinicaltrials.gov) - P2 | N=326 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Pharmacological Interventions for Hereditary Transthyretin-Related Amyloidosis With Polyneuropathy: Systematic Review and Network Meta-Analysis. (PubMed, Eur J Neurol) - "Gene-silencing therapies were more efficacious, although these findings should be regarded as hypothesis-generating given the scarcity of data, lack of head-to-head trials, and clinical heterogeneity across trials."

Journal • Retrospective data • Review • Amyloidosis • CNS Disorders • Pain

Context-of-use-Guided Development and Validation of a Transthyretin Immunoassay: A Framework for Biomarker Assay Design. (PubMed, AAPS J) - "Clinical trials with Eplontersen, a TTR-targeting antisense oligonucleotide, required an assay with a context of use differing from existing assay, requiring a more sensitive method...The development process highlights generalizable principles in biomarker assay design, including matrix considerations, variability analysis, and curve optimization. These insights provide a transferable framework for biomarker method development in regulated environments."

Biomarker assay • Journal • Amyloidosis • Cardiac Amyloidosis

Baseline characteristics of patients with transthyretin amyloidosis with cardiomyopathy in the CARDIO-TTRansform trial of eplontersen. (PubMed, Eur J Heart Fail) - "The baseline characteristics of CARDIO-TTRansform were consistent with previous ATTR-CM trials; however, CARDIO-TTRansform evaluated patients with a wide range of disease severity and receiving the contemporary standard of care for ATTR-CM. Overall, blinded baseline data suggest that CARDIO-TTRansform provides a unique opportunity to determine the clinical benefits of eplontersen in a contemporary setting and in clinically relevant subgroups of patients with ATTR-CM."

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

ATTRiumph: A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM. (clinicaltrials.gov) - P2 | N=326 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Rationale and Design of CARDIO-TTRansform, a Phase 3 Trial of Eplontersen in Transthyretin Amyloid Cardiomyopathy. (PubMed, Circ Heart Fail) - P3 | "URL: https://www.clinicaltrials.gov; Unique identifier: NCT04136171. URL: http://ClinicalTrialsRegister.eu; Unique identifier: EudraCT number 2019-002835-27."

Clinical • Journal • P3 data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

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...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%...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