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

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

Current and emerging treatment options for transthyretin amyloid cardiomyopathy. (PubMed, Heart) - "Treatments available in clinical practice include TTR stabilisers (tafamidis and acoramidis), which prevent the dissociation of TTR tetramer into monomers and oligomers that subsequently form amyloid fibrils, and gene-silencing therapies (patisiran, inotersen and vutrisiran), which suppress the hepatic synthesis of TTR, which is the amyloid precursor protein. Novel treatment strategies that are at various stages of development include Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 gene-editing technology (nexiguran ziclumeran), which, if successful, offers the prospect of a single-dose treatment, and monoclonal (cormitug and ALXN220) and pan-amyloid antibodies (AT-02) that seek to target and remove amyloid fibrils that have deposited in the myocardium...The success of ATTR-specific disease-modifying therapies has already altered the treatment landscape and changed the perception of ATTR amyloidosis from a progressive and fatal disease to one that is..."

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

Serum Transthyretin as a Biomarker of Treatment Response in ATTR Cardiomyopathy. (PubMed, J Am Coll Cardiol) - No abstract available

Biomarker • Journal • Cardiomyopathy • Cardiovascular

Early Increase in Serum Transthyretin by Acoramidis Independently Predicts Improved Survival in TTR Amyloid Cardiomyopathy. (PubMed, J Am Coll Cardiol) - P3 | "Acoramidis-mediated early ΔTTR is independently associated with improved survival after adjusting for known predictors. This provides strong evidence for a direct association between a prompt and sustained increase in sTTR upon initiation of treatment with acoramidis and survival. Early changes in sTTR could be used as a marker of the degree of TTR stabilization. (Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Cardiomyopathy [ATTRibute-CM]; NCT03860935)."

Clinical • Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

ATTRibutes of change: advances in treating and monitoring ATTR-CM (HEART FAILURE 2025) - "Beyonttra® is approved by FDA and EMA, but not yet registered by Serbian Health Authority. SmPC is available at the booth MA-M_ACR-ALL-0093-3 / MA-M_ACR-RS-0004-1 / March 2025"

Cardiovascular • Congestive Heart Failure • Heart Failure

Relative efficacy of tafamidis, acoramidis, patisiran and vutrisiran in patients with transthyretin cardiac amyloidosis: a network meta-analysis (HEART FAILURE 2025) - "Tafamidis demonstrated the highest efficacy in improving survival, reducing cardiovascular hospitalizations, and enhancing functional capacity and quality of life in patients with ATTR-CA, qualifying as the primary treatment choice. Vutrisiran and acoramidis emerged as viable alternatives."

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

Acoramidis improves serum TTR levels in patients with wild-type or variant transthyretin amyloid cardiomyopathy - results from ATTRibute-CM (HEART FAILURE 2025) - P3 | "In ATTRibute-CM, baseline sTTR levels, a measure of TTR stability, were lower in ATTRv-CM than in ATTRwt-CM. In both subgroups, acoramidis treatment induced a rapid increase in sTTR levels by Day 28, with comparable sTTR levels achieved in both subgroups from Day 28 through Month 30."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Acoramidis treatment is associated with a lower incidence of atrial fibrillation/atrial flutter events in patients with ATTR-CM: post-hoc analyses of the ATTRibute-CM trial (HEART FAILURE 2025) - P3 | "In ATTRibute-CM, acoramidis treatment was associated with reduced hospitalizations and adverse events due to AF/AFL, compared with placebo. This may lead to potential benefits on arrhythmia-associated morbidity that is frequently observed in patients with ATTR-CM."

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

Effect of acoramidis on all-cause mortality, cardiovascular hospitalization and NT-proBNP in variant ATTR-CM - results from ATTRibute-CM (HEART FAILURE 2025) - "In variant ATTR-CM, acoramidis treatment administered for 30 months led to a substantial reduction (> 50%) in the composite of ACM/CVH, ACM and CVH. This improvement was accompanied by favourable effects on NT-proBNP levels."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Effect of acoramidis on functional capacity and quality of life in patients with variant ATTR-CM: results from ATTRibute-CM (HEART FAILURE 2025) - "In patients with variant ATTR-CM, acoramidis treatment administered for 30 months resulted in a clinically significant slower decline in functional capacity and QoL compared with placebo, consistent with the overall results from ATTRibute-CM."

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

Cause of death in patients with transthyretin amyloid cardiomyopathy (ATTR-CM): findings from the ATTRibute-CM study (HEART FAILURE 2025) - "In the ATTRibute-CM study, total deaths were numerically lower with acoramidis compared with placebo. The relative risk reduction of 30% in CVM by Month 30 was driven predominantly by a reduction in heart failure-related deaths."

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

Acoramidis Reduced Incidence of Atrial Fibrillation Events in Patients with ATTR-CM (GlobeNewswire) - P3 | N=632 | ATTRibute-CM (NCT03860935) | Sponsor: Eidos Therapeutics, a BridgeBio company | "In a post-hoc analysis of ATTRibute-CM, acoramidis reduced the annual frequency of CVH due to AF/AFL by 43% compared to placebo and reduced the incidence of new-onset AF/AFL by 17% in the subgroup with no prior history of AF compared to placebo; In the ATTRibute-CM study, acoramidis demonstrated the most rapid benefit seen in any Phase 3 study of ATTR-CM to date in both ATTRv-CM and ATTRwt-CM patients: In as few as 3 months, the time to first event (ACM or CVH) durably separated relative to placebo; A 42% reduction in composite ACM and recurrent CVH events relative to placebo at Month 30; A 50% reduction in the cumulative frequency of CVH events relative to placebo at Month 30."

P3 data • Amyloidosis • Cardiomyopathy

Acoramidis-mediated improvement in NT-proBNP at month 30 compared with placebo in patients with ATTR-CM: results from the ATTRibute-CM study (ESC-WCC 2025) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiovascular

Relative efficacy of tafamidis, acoramidis, patisiran and vutrisiran in patients with transthyretin cardiac amyloidosis: a network meta-analysis (ESC-WCC 2025) - No abstract available

Retrospective data • Cardiac Amyloidosis • Cardiovascular

Early and Sustained Increase in Serum TTR Levels by Acoramidis Independently Predicted Improved Survival in the ATTRibute-CM Study (GlobeNewswire) - P3 | N=632 | ATTRibute-CM (NCT03860935) | Sponsor: Eidos Therapeutics, a BridgeBio company | "Findings from the analysis included: Treatment with acoramidis resulted in a sharp, significant early rise in serum TTR levels (mean 9.1 mg/dL) within 28 days which was sustained throughout the 30-month treatment period; For every 5-mg/dL increase in serum TTR level, the Cox proportional hazards model predicted a relative risk reduction of mortality of 26.6% and the logistic model predicted a relative reduction of 31.6% in odds of death through Month 30; An early increase in serum TTR levels on Day 28 of dosing was associated with reduced all-cause mortality (ACM) in univariate analysis, an association which persisted in multivariate analysis independent of TTR variant status, baseline NYHA functional class, baseline NAC stage, and baseline serum TTR levels."

P3 data • Amyloidosis • Cardiomyopathy

Cost-Effectiveness of Transthyretin Stabilizing Agents for the Treatment of Transthyretin Amyloid Cardiomyopathy (ATTR-CM) (ISPOR 2025) - "OBJECTIVES: Tafamidis and acoramidis are transthyretin stabilizing agents (TTR-SA) indicated for transthyretin amyloid cardiomyopathy (ATTR-CM). Treatment with TTR-SAs plus SC led to improved health outcomes at higher costs compared to SC alone. At the assumed price, TTR-SAs would require a substantial discount to achieve commonly used cost-effectiveness thresholds in the US."

Cost effectiveness • HEOR • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

BridgeBio to Present Clinical Outcomes, Quality of Life Measures and Incidence of Atrial Fibrillation Events in Patients with ATTR-CM from the ATTRibute-CM Study at the Annual Congress of the Heart Failure Association of the ESC (GlobeNewswire) - "BridgeBio Pharma...announced today that one rapid-fire abstract and two moderated ePosters on the clinical outcomes and quality of life measures provided by acoramidis in variant transthyretin amyloid cardiomyopathy (ATTR-CM) and one moderated ePoster on a post-hoc analysis of the lower incidence rate of atrial fibrillation-related events in patients with ATTR-CM, all from the ATTRibute-CM study will be shared at the Annual Congress of the Heart Failure Association of the ESC (Heart Failure 2025), taking place in Belgrade, Serbia on May 17 - 20, 2025....In addition to the four abstracts, three moderated ePosters will be shared on the disease progression of ATTR-CM in a real-world setting, a retrospective cohort study on manifestation to diagnosis of ATTR-CM, and data on the cause of death of ATTR-CM patients in the ATTRibute-CM study."

P3 data • Amyloidosis • Cardiomyopathy

First Participant Dosed with Acoramidis in ACT-EARLY, the First Ever ATTR Primary Prevention Study (GlobeNewswire) - "BridgeBio Pharma, Inc...announced today that the first asymptomatic participant with a known pathogenic transthyretin (TTR) variant, that may lead to transthyretin amyloid disease (either cardiomyopathy, ATTR-CM, polyneuropathy, ATTR-PN, or both), has been dosed in ACT-EARLY with acoramidis. Acoramidis is a selective, small molecule, orally administered near-complete (≥90%) TTR stabilizer."

Trial status • Cardiomyopathy

Acoramidis has a beneficial effect compared with placebo on change from baseline in NAC ATTR stage at month 30 in patients with ATTR-CM: results from the ATTRibute-CM study (ESC-WCC 2025) - No abstract available

Clinical • Cardiovascular

Acoramidis leads to clinically meaningful improvements from baseline in NT-proBNP and 6-minute walk distance in patients with transthyretin amyloid cardiomyopathy: observations from ATTRibute-CM (ESC-WCC 2025) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Acoramidis reduces cardiovascular mortality (CVM): results at month 42 from the ATTRibute-CM open-label extension (OLE) study (ESC-WCC 2025) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiovascular

BridgeBio Reports First Quarter 2025 Financial Results and Business Updates (GlobeNewswire) - "The first full quarter of Attruby net product revenue was $36.7 million. As of April 25, 2025, 2,072 unique patient prescriptions for Attruby have been written by 756 unique healthcare providers since FDA approval in November 2024....More data on the benefit of Attruby will be shared at the European Society of Cardiology Heart Failure Congress in May 2025 and at additional medical meetings in the second half of 2025."

Clinical • Commercial • Cardiomyopathy

Case of steroid-induced DKA (ENDO 2025) - "Her outpatient diabetes medication included Januvia 25 mg and 10 units of insulin...Labs revealed hyperglycemia and anion gap metabolic acidosis from septic shock: Glucose: 284 mg/dL(70-90 mg/dL), bicarb15 mEq/L (22-28 mEq/L), BHB 0.1 mmol/L (0.1-0.3 mmol/L), AG 10.7 mmol/L (4-11 mmol/L), Cr 3.26mg/dL (0.50-1.10 mg/dL), lactic acid 3.0 mmol/L (0.5-2.0 mmol/L), pH 7.33 (7.35-7.45), pCO2 19 mmHg(33-45 mmHg) and pO2 115mmHg (75-105 mmHg)... The reported case details a patient with uncontrolled T2DM who developed steroid-induced DKA during treatment for septic shock. The two main mechanisms that could contribute to steroid-induced DKA include elevated peripheral insulin resistance at muscle and adipose levels through GLUT4 translocation inhibition and secondly increased glucose production through glycogenolysis and gluconeogenesis. Per the literature review, there are very few reported cases of steroid-induced DKA in T2DM patients."

Clinical • Diabetes • Metabolic Disorders • Nephrology • Obesity • Pain • Septic Shock • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus • SLC2A4

Antibody ALXN2220 (Formerly NI006) for the Treatment of Transthyretin Cardiac Amyloidosis. (PubMed, Cardiol Rev) - "The agents currently approved by the United States Food and Drug Administration-tafamidis and acoramidis-are transthyretin stabilizers that prevent the breakdown of the physiologic transthyretin tetramer into fibril-forming monomers. A multinational, placebo-controlled phase 3 trial (DepleTTR-CM) is ongoing to assess long-term efficacy, functional outcomes, and survival impact. These results are expected to provide critical real-world evidence on ALXN2220's role in transthyretin cardiac amyloidosis management."

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

Acoramidis approved to treat wild-type or variant transthyretin amyloidosis in adults with cardiomyopathy (GOV.UK) - "The Medicines and Healthcare products Regulatory Agency (MHRA) has approved the medicine acoramidis (Beyonttra) to treat adult patients with cardiomyopathy (damage to the heart muscle) caused by variant or wild-type transthyretin amyloidosis (ATTR-CM). Acoramidis has been approved via a fast-track approval process for medicines, known as the International Recognition Procedure (IRP), following approval by the European Medicines Agency (EMA) earlier this year....This approval is supported by evidence from an international, randomised, double-blind, placebo-controlled clinical study involving 632 patients with either variant or wild-type ATTR-CM with symptoms of heart failure."

MHRA approval • Cardiomyopathy