Attruby (acoramidis) / BridgeBio, AstraZeneca, Bayer - LARVOL DELTA

Efficacy of Acoramidis in Wild-Type and Variant Transthyretin Amyloid Cardiomyopathy: Results From ATTRibute-CM and Its Open-Label Extension. (PubMed, JAMA Cardiol) - P3 | "These hypothesis-generating results indicate that further studies are warranted to better characterize the therapeutic benefit of acoramidis in variant subgroups. ClinicalTrials.gov Identifiers: NCT03860935; NCT04988386."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Transthyretin Amyloid Cardiomyopathy: The Plot Thickens as Novel Therapies Emerge. (PubMed, US Cardiol) - "Finally, we explore key unresolved questions, including the need for head-to-head comparative trials, the potential role of combination therapy, and the optimal timing for initiating treatment as earlier recognition becomes more common. As novel therapies gain approval this review serves as a timely, focused resource to support clinicians managing ATTR-CM."

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

Iron‑regulatory gene variants and their association with clinical phenotypes in Nigerian patients with sickle cell disease (ASH 2025) - "Results remained consistent afteradjusting for age.For lifetime transfusion burden, both UVA and MVA identified two significant SNPs: rs4667289, associatedwith higher transfusion burden (β = 2.6, 95% CI: 0.04–5.2, p = 0.047) and rs11568344, associated withlower transfusion burden (β = –1.8, 95% CI: –3.5 to –0.36, p = 0.02).Genotype distributions for the five significant SNPs were as follows: rs10177654 (SLC40A1, transcriptionfactor binding site), TT(WT) 12 (20.3%), TC 30 (50.8%), CC 17 (28.8%); rs10188230 (SLC40A1, intron variant),TT (WT) 32 (54.2%), TC 22 (37.3%), CC 5 (8.5%); rs10218795 (HJV, intron variant), CC (WT) 22 (37.3%),TC 29 (49.2%), TT 8 (13.6%); rs4667289 (SLC40A1 proximal intergenic), GG (WT) 46 (78.0%), AG 10 (16.9%),AA 3 (5.1%); rs11568344 (SLC40A1 splice region variant), GG (WT) 47 (79.7%), AG 9 (15.3%), AA 3 (5.1%).Compared with the homozygous WT, patients with rs10188230 had a lower median TS (21.65% vs. 43.3%,p = 0.04), while those with rs4667289 had..."

Clinical • SLC40A1

Transthyretin Cardiac Amyloidosis Evaluation and Management: 2025 ACC Concise Clinical Guidance. (PubMed, J Am Coll Cardiol) - "Finally, individuals with transthyretin amyloid cardiomyopathy have benefitted from advances in broadly effective heart failure therapies, namely mineralocorticoid receptor antagonists and sodium glucose-cotransporter 2 inhibitors, as well as specific disease-modifying therapies with transthyretin stabilizers, tafamidis and acoramidis, and the transthyretin silencer vutrisiran. The purpose of this Concise Clinical Guidance is to offer updated strategies to clinicians, reflecting the expanding therapeutic landscape, and reinforcing best practices for the diagnosis and management of transthyretin amyloid cardiomyopathy with a focus on choice of disease-modifying therapies, heart failure therapies, and future directions."

Clinical guideline • Journal • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Transplantation

Comparative Efficacy and Safety of Vutrisiran, Acoramidis, Tafamidis in Transthyretin Amyloid Cardiomyopathy: A Network Meta-Analysis (AHA 2025) - "Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, life-threatening disorder caused by transthyretin deposition in cardiac tissue. Vutrisiran demonstrated the most consistent survival and biomarker benefits, while Patisiran ranked highest in overall efficacy. Acoramidis showed strong improvement in functional capacity but varied across domains."

Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Adverse events profile of Transthyretin stabilizers in Transthyretin Amyloid Cardiomyopathy - A Meta-Analysis of randomised control trials (AHA 2025) - "Transthyretin (TTR) stabilizers such as Tafamidis and Acoramidis are reported to have increased clinical benefits; however, comparison of safety profiles remains limited. TTR stabilizers showed a favorable safety profile in ATTR-CM, with reduced rates of serious and cardiac failure-related adverse events and no increase in overall TEAEs. These findings support their clinical safety; however, limited study numbers and sample sizes warrant cautious interpretation and highlight the need for further research."

Adverse events • Retrospective data • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Comparative Safety and Efficacy of Acoramidis Versus Tafamidis in Transthyretin Amyloid Cardiomyopathy: A Systematic Review (AHA 2025) - "Both Acoramidis and Tafamidis are quite effective in ATTR-CM. Acoramidis may generate more meaningful decreases in cardiovascular hospitalizations and biomarker improvements, with a positive trend in survival at extended terms. Comparative head-to-head trials are needed to determine comparative superiority.Keywords:Acoramidis, Tafamidis, ATTR-CM, Transthyretin Cardiomyopathy, All cause mortality, 6-minute walk distance, Cardiovascular Outcomes, Systematic review, Cardiology"

Clinical • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Fatigue • Infectious Disease • Nephrology

CA.APB.01: Electrophysiology, Amyloidosis & Precision Cardiology (AHA 2025) - "Several studies examine drug safety and efficacy (e.g., tafamidis, acoramidis, vutrisiran), while others investigate mechanisms of cardiac development, pacing strategies, and novel therapeutic approaches like gene transfer. This is not a CE accredited session. Poster Professor: Stavros Stavrakis (UNIVERSITY OF OKLAHOMA)"

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure • Infectious Disease • Novel Coronavirus Disease

Serum Transthyretin Levels at Day 28 are Associated with Cardiovascular Outcomes: Insights From the ATTRibute-CM Study (AHA 2025) - "Acoramidis, a near-complete (≥90%) TTR stabilizer, demonstrated a rapid and sustained increase from baseline in sTTR by Day 28 and reduced risk of cardiovascular outcomes in patients with ATTR-CM.Hypothesis: Acoramidis-mediated early increase in sTTR levels ≥20 mg/dL (lower limit of normal) at Day 28 reduces risks of CVM and cardiovascular-related hospitalizations (CVH) in patients with ATTR-CM. Analyses were conducted in the ATTRibute-CM modified intention-to-treat (mITT) population (acoramidis: 409; placebo: 202)... Across treatment groups, sTTR levels above normal range (≥20 mg/dL) at Day 28 were associated with a lower risk of cardiovascular outcomes at Month 30, when compared with sTTR levels below normal range (<20 mg/dL). Thus, these observations demonstrate that higher sTTR levels over time may have the potential for clinical benefits in both CVM and CVH."

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

Acoramidis Improved Clinical Outcomes, Function, Quality of Life and NT-proBNP in Patients With Transthyretin Amyloid Cardiomyopathy Regardless of Atrial Fibrillation Status at Baseline (AHA 2025) - P3 | "Acoramidis improved clinical outcomes (ACM, CVH), functional status, QoL and NT-proBNP levels relative to placebo in participants with ATTR-CM, regardless of AF/AFL diagnosis at baseline."

Clinical • Clinical data • HEOR • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Acoramidis Effect on All-Cause Mortality in Patients with p.V142I (V122I) Variant ATTR-CM: Findings From the ATTRibute-CM Study (AHA 2025) - P3 | "These findings have biologic plausibility and may reflect the near-complete stabilization observed experimentally with acoramidis in p.V142I ATTR fibrils. These observations require confirmation in larger cohort studies."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Acoramidis Reduces All-Cause Mortality and Cardiovascular-Related Hospitalizations Through Month 42 in Transthyretin Amyloid Cardiomyopathy Across All Pre-specified Patient Subgroups (AHA 2025) - "The analyses of ACM/first CVH (Figure 1) and ACM (Figure 2) through M42 consistently favored patients initially randomized to acoramidis across all patient subgroups, including those based on sex, age, country, ATTR-CM genotype, baseline NT-proBNP, baseline eGFR, NYHA class, and NAC stage. The largest effect size for the reduction in ACM/first CVH (HR <0.50) was observed in the following subgroups: female, non-Caucasian patients, variant ATTR-CM, or NAC stage 2.ConclusionsThe long-term benefit of acoramidis was consistently shown in patients initially randomized to acoramidis treatment compared with placebo to acoramidis switch after 30 months across multiple clinically relevant subgroups, underscoring the importance of early initiation of acoramidis to reduce the long-term risk of ACM or CVH."

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

Phenotypic Evolution of Early to Late Cardiac Amyloidosis with Serial Cardiac Magnetic Resonance (AHA 2025) - "The patient was diagnosed with wild type transthyretin CA and started on acoramidis.DiscussionTimely diagnosis of CA is crucial, as therapies are more effective early in disease...Our patient had a Mayo score of 4 (screened out) and AMYLI score of 4.3 (not screened out), highlighting the clinical suspicion that can persist despite non-diagnostic testing.Conclusions This case illustrates that the "warranty period" of a CMR that does not show clear signs of CA despite reasonably high clinical suspicion may be under 5 years. Further investigations are necessary to define progression and screening intervals."

Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Acoramidis Reduces the Risk of All-Cause Mortality and Cardiovascular-Related Hospitalization Compared With Placebo in Participants With Transthyretin Amyloid Cardiomyopathy and Early-Stage Heart Failure Regardless of Atrial Fibrillation History: Insights From ATTRibute-CM (AHA 2025) - P3 | "Lower risk of clinical outcomes (ACM and CVH) was observed with acoramidis in patients with early-stage HF, regardless of the presence or absence of an AF/AFL diagnosis at baseline."

Clinical • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Clinical Effects of Acoramidis Versus Placebo in the ATTRibute-CM Study: Observations from the Intention-to-Treat Population (AHA 2025) - P3 | "In the ITT (n=421 acoramidis; n=211 placebo), acoramidis significantly improved all evaluated clinical outcomes vs placebo, with RRs (95% confidence interval [CI]) of 0.74 (0.56, 0.98) and 0.57 (0.42, 0.77) for ACM and first hospitalization for heart failure, respectively (Figure). 6MWD and KCCQ-OSS were improved with acoramidis compared with placebo, with LSM differences (95% CI) of 40.81 (22.55, 59.07) and 10.20 (6.30, 14.10), respectively. The RRs (95% CI) in achieving a ≥5% deterioration and ≥5% improvement in KCCQ-OSS with acoramidis vs placebo were 0.77 (0.68, 0.88) and 1.76 (1.19, 2.59).Conclusion(s): The present ITT analysis showed consistent favorable results across all subgroups studied, confirming the efficacy of acoramidis in all patients with ATTR-CM, including patients with kidney impairment."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

A Case of Concomitant Wild-Type Transthyretin and Systemic Light Chain Amyloidosis Involving Separate Organs (AHA 2025) - "He completed 6 cycles of cyclophosphamide, bortezomib, dexamethasone and daratumumb with a very good hematologic partial response. For his ATTR-CA, he was initiated on acoramidis, spironolactone, and empagliflozin with improvement in his symptoms and cardiac biomarkers over the following months.DiscussionThis is a case of concurrent ATTRwt-CA with systemic AL amyloidosis and kidney involvement...A radionuclide scan for suspected cardiac amyloidosis should never be ordered in isolation. In the present case, had light chains not been ordered concurrently, the positive radionuclide scan may have led to a premature diagnosis of isolated ATTR-CA, but missed a crucial diagnosis of plasma cell dyscrasia."

Clinical • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiovascular • Hematological Malignancies • Multiple Myeloma • Plasmacytoma • Pulmonary Disease

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

Acoramidis Lowers NT-proBNP in a Larger Proportion of ATTRibute-CM Study Participants With Transthyretin Amyloid Cardiomyopathy Compared with Placebo, Independent of Atrial Fibrillation Status (AHA 2025) - P3 | "In ATTRibute-CM, the proportion of participants with improved NT-proBNP at Month 30 was consistently around 15 percentage points higher with acoramidis than placebo, regardless of AF/AFL status at BL or during the study. The ongoing open-label extension study may offer insights into the durability of this effect and its long-term clinical consequences."

Clinical • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Acoramidis Reduces All-Cause Mortality and First Cardiovascular Hospitalization in Patients with Variant Transthyretin Amyloid Cardiomyopathy: Results From the ATTRibute-CM Study (AHA 2025) - "These previously unreported findings support the hypothesis that near complete TTR stabilization observed experimentally with acoramidis across multiple TTR mutations translates into improvement in long-term outcomes. Further validation by individual TTR variant is warranted."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Acoramidis for the Treatment of Transthyretin Cardiac Amyloidosis. (PubMed, Cardiol Rev) - "Following closely on the heels of tafamidis, the United States Food and Drug Administration approved acoramidis for patients with ATTR cardiac amyloidosis in 2024. Acoramidis also improved clinical outcomes such as all-cause mortality and cardiovascular hospitalizations; improved biomechanistic parameters such as 6-minute walk distances, n-terminal pro B-type natriuretic peptide levels, stabilization of myocardial thickness; as well as improved patient-reported outcomes through improved Kansas City Cardiomyopathy Questionnaire scores. The results of the ACT-EARLY trial exploring the preventive benefits of acoramidis are eagerly awaited."

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

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

Effect of Acoramidis on Recurrent and Cumulative Cardiovascular Outcomes in ATTR-CM: Exploratory Analysis From ATTRibute-CM. (PubMed, J Am Coll Cardiol) - "Acoramidis significantly reduced the cumulative burden of CV outcomes in ATTR-CM over 30 months. Numerically fewer events were observed with acoramidis vs placebo by month 1, and the difference increased progressively over time, resulting in 53 events avoided per 100 treated patients at month 30. Almost one-fourth of the cumulative CV events occurred within the first 6 months. These exploratory findings suggest that cumulative event burden may occur early, highlighting the importance of timely evaluation, diagnosis and treatment in ATTR-CM."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

ACORAMIDIS UNDER THE MICROSCOPE: EXPOSING HIDDEN DANGERS AND ADVERSE EVENTS (CHEST 2025) - "The findings indicate that Acoramidis is associated with several notable AEs, with acute kidney injury and cardiac failure being the most frequently reported. The high percentage fraction of atrial fibrillation was also a notable finding. AEs in the elderly population (65-85 years) highlights the need for careful monitoring in this age group CLINICAL IMPLICATIONS: This stduy emphasize the importance of ongoing pharmacovigilance."

Adverse events • Acute Kidney Injury • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Musculoskeletal Pain • Nephrology • Renal Disease

PULMONARY HYPERTENSION IN THE SETTING OF TRANSTHYRETIN CARDIAC AMYLOIDOSIS: A CASE REPORT OF A RARE DISEASE (CHEST 2025) - "[3] Therapeutic options for this patient include Tafamidis or Acoramidis, TTR protein stabilizers, which can help slow disease progression. As shown herein, ATTR cardiac amyloidosis can lead to severe CpC-PH. Diagnosis involves serologic testing for AL amyloidosis then PYP scan highly specific for ATTR. TTR protein stabilizers may help slow disease progression."

Case report • Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Heart Failure • Monoclonal Gammopathy • Nephrology • Pulmonary Arterial Hypertension • Pulmonary Disease • Rare Diseases • Renal Disease • Respiratory Diseases

Disease-Modifying Therapies for Transthyretin Amyloid Cardiomyopathy: A Systematic Review and Meta-Analysis. (PubMed, Arq Bras Cardiol) - "TTR stabilizers significantly reduced all-cause mortality and hospitalizations in patients with ATTR-CM compared with placebo. These benefits were not observed with TTR silencers, potentially due to shorter follow-up durations in the studies evaluated. Both therapies improved functional status and serum levels of NT-proBNP."

Biomarker • Clinical • Journal • Retrospective data • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular