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

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

Sodium-glucose cotransporter 2 inhibitors in transthyretin amyloid cardiomyopathy: navigating potential benefits and uncertainties. (PubMed, Curr Med Res Opin) - "While tafamidis and acoramidis have emerged as effective therapies, residual cardiovascular risk persists, highlighting the need for adjunctive treatments. Future directions involve elucidating mechanisms of action, exploring personalized treatment strategies, and leveraging big data analytics for real-world insights. SGLT2i's potential to transform ATTR-CM management underscores their promise, though robust trials are imperative to validate findings and optimize clinical applications."

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

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) - No abstract available

Retrospective data • Cardiac Amyloidosis • Cardiovascular

Acoramidis improves serum TTR levels in patients with wild-type or variant transthyretin amyloid cardiomyopathy - results from ATTRibute-CM (HEART FAILURE 2025) - No abstract available

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) - No abstract available

Clinical • Retrospective data • Atrial Fibrillation • Cardiovascular

Effect of acoramidis on all-cause mortality, cardiovascular hospitalization and NT-proBNP in variant ATTR-CM - results from ATTRibute-CM (HEART FAILURE 2025) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiovascular

Effect of acoramidis on functional capacity and quality of life in patients with variant ATTR-CM: results from ATTRibute-CM (HEART FAILURE 2025) - No abstract available

Clinical • HEOR • Cardiac Amyloidosis • Cardiovascular

Etiological Treatment of Cardiac Amyloidosis: Standard of Care and Future Directions. (PubMed, Curr Heart Fail Rep) - "The standard of care for ATTR-CA include agents capable of selectively stabilizing the precursor protein (e.g., tafamidis), whereas the plasma cell clone is the main target of chemotherapy for AL-CA...Recent data from ATTRibute-CM led to the approval of acoramidis, whereas patisiran received refusal based on the APOLLO-B trial. Novel CRISPR-Cas9-based drugs (i.e., NTLA-2001) hold great potential in the setting of ATTR-CA...However, the investigation of monoclonal antibodies targeting misfolded ATTR (e.g., PRX004, NI301A) or AL (e.g., birtamimab, anselamimab) has led to encouraging results. Various cutting-edge strategies are being tested for treatment of CA and may change the prognostic landscape of this condition in the next years."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Hematological Disorders

Acoramidis for Transthyretin Amyloid Cardiomyopathy: Open-Label Extension Study Long-Term Follow-Up. (PubMed, J Card Fail) - No abstract available

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Transthyretin as a therapeutic target: the future of disease-modifying therapies for Alzheimer's disease. (PubMed, Mol Biol Rep) - "Recent research has revealed that TTR is gradually showcasing its promise in neuroprotection and neuronal viability in AD by binding with Aβ and mitigating its neurotoxic effects. Current preclinical and clinical studies also support that TTR is actively involved in maintaining the blood-brain barrier (BBB) integrity and maintain neurotransmitter balance, all of which offer significant therapeutic promise through TTR stabilizers, such as Tafamidis, Acoramidis, and Vutrisiran, highlighting their potential in AD treatment This review concludes that TTR plays bidirectional role and gaining interest as a potential biomarker, though several challenges must be addressed before it can be established a novel therapeutic target in AD management in the modern era of drug discovery."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders

IMPROVEMENT IN MEASURES OF QUALITY OF LIFE AMONG PATIENTS RECEIVING TARGETTED THERAPY FOR ATTR AMYLOIDOSIS: A META-ANALYSIS OF DATA FROM RANDOMIZED CONTROLLED TRIALS - Shubhashis Saha (ACC 2025) - "Background: Novel drugs like patisiran, vutrisiran, tafamidis, acoramidis, eplontersen, and inotersen reduce the synthesis and deposition of TTR amyloid fibrils in patients with cardiac amyloidosis. Contemporary drugs for cardiac amyloidosis improved quality of life and 6MWT, while having a good safety profile. Although they are usually classified as secondary outcomes in many clinical trials, these improvements would be more relevant to the patients in short to medium term."

HEOR • Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

LACK OF IMPROVEMENT IN CARDIAC FUNCTION AMONG PATIENTS RECEIVING TARGETTED THERAPY FOR ATTR AMYLOIDOSIS: A META-ANALYSIS OF DATA FROM RANDOMIZED CONTROLLED TRIALS - Revati Varma (ACC 2025) - "Background: Novel drugs like patisiran, vutrisiran, tafamidis, acoramidis, eplontersen, and inotersen reduce the synthesis and deposition of TTR amyloid fibrils in patients with cardiac amyloidosis (CA). Contemporary drugs for CA did not result in changes in the cardiac structure on echocardiographic parameters while having a good safety profile."

Retrospective data • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

ACORAMIDIS IMPROVES SERUM TTR LEVELS IN PATIENTS WITH WILD-TYPE OR VARIANT TRANSTHYRETIN AMYLOID CARDIOMYOPATHY - Margot Davis (ACC 2025) - "Despite greater TTR destabilization and lower baseline sTTR in ATTRv-CM pts, acoramidis treatment induced a greater proportional increase in sTTR and achieved similar absolute sTTR levels as ATTRwt-CM pts. In a pre-specified analysis, this resulted in statistically significant better outcomes in both ATTRv-CM and ATTRwt-CM pts."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

ACORAMIDIS-MEDIATED EARLY INCREASE IN SERUM TRANSTHYRETIN LEVEL REDUCES CARDIOVASCULAR-RELATED HOSPITALIZATIONS AND MORTALITY: INSIGHTS FROM THE ATTRIBUTE-CM STUDY - Nitasha Sarswat (ACC 2025) - "Incremental increases in sTTR levels on Day 28, achieved with acoramidis, may independently predict greater reduction in risks of CVM and of first CVH in patients with ATTR-CM."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

IN PARTICIPANTS TREATED WITH ACORAMIDIS, ADDITION OF CONCOMITANT TAFAMIDIS DID NOT FURTHER INCREASE SERUM TTR LEVELS - Mathew S. Maurer (ACC 2025) - "In pts with transthyretin amyloid cardiomyopathy, treatment with acoramidis significantly increased sTTR levels compared to PBO and PBO+TAF. Addition of TAF to acoramidis did not show any further increase in sTTR levels, indicating no additional stabilization of sTTR. Safety of concomitant acoramidis+TAF was similar to the overall safety profile of acoramidis."

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

ROBUSTNESS OF PRIMARY ENDPOINT EFFICACY RESULTS WITH ACORAMIDIS IN ATTR-CM IN THE ATTRIBUTE-CM STUDY: PRE-SPECIFIED NT-PROBNP SENSITIVITY ANALYSES - Jan Griffin (ACC 2025) - "Pre-specified sensitivity analyses using higher NT-proBNP thresholds showed consistent efficacy favoring acoramidis in pts with ATTR-CM. This confirms the robustness of the acoramidis treatment effect regardless of NT-proBNP progression thresholds."

Clinical • Cardiovascular

ACORAMIDIS IMPROVES NYHA CLASS AT MONTH 30 VERSUS PLACEBO IN PATIENTS WITH ATTR-CM: RESULTS FROM THE ATTRIBUTE-CM STUDY - Richard F. Wright (ACC 2025) - "Acoramidis treatment resulted in a greater proportion of pts whose NYHA Class was stable/improved at Month 30 vs PBO, indicating better stabilization in their heart failure symptom and functional status."

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

CARDIOVASCULAR OUTCOMES OF TARGETED THERAPIES FOR TRANSTHYRETIN-ASSOCIATED AMYLOID CARDIOMYOPATHY - Sammudeen Ibrahim (ACC 2025) - "Our study highlights the efficacy of tafamidis, vutrisiran, acoramidis, and diflunisal in significantly improving all-cause mortality, OHT, and CV hospitalizations in patients with ATTR-CM. Conversely, patisiran did not demonstrate significant benefits on the evaluated outcomes."

Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

PRIMARY ENDPOINT EFFICACY RESULTS IN THE ATTRIBUTE-CM STUDY: PRE-SPECIFIED SENSITIVITY ANALYSES ADDRESSED TAFAMIDIS USE - Daniel P. Judge (ACC 2025) - "Background: In ATTRibute-CM, acoramidis (an investigational transthyretin stabilizer) met its 4-step primary efficacy endpoint (all-cause mortality, cardiovascular-related hospitalization, change in NT-proBNP and 6-minute walk distance vs placebo [PBO]; p<0.0001). Pre-specified analyses showed consistent results with the primary analysis, demonstrating that the concomitant use of TAF did not alter the statistical significance of the primary efficacy endpoint."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Acoramidis: First Approval. (PubMed, Drugs) - "This article summarizes the milestones in the development of acoramidis leading to its first approval in the USA for the treatment of the cardiomyopathy of wild-type or variant TTR-mediated amyloidosis in adults to reduce cardiovascular death and cardiovascular-related hospitalization. In the EU, a positive opinion has been adopted for the treatment of wild-type or variant transthyretin amyloidosis in adult patients with cardiomyopathy."

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

Acoramidis Shows Statistically Significant Improvements in Cardiovascular Outcomes in Patients with Variant ATTR-CM (GlobeNewswire) - P3 | N=632 | ATTRibute-CM (NCT03860935) | Sponsor: Eidos Therapeutics, a BridgeBio company | "BridgeBio Pharma...presented results showing statistically significant improvements in clinical outcomes as compared to placebo for time to all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) in both variant (ATTRv) and wild-type (ATTRwt) transthyretin amyloid cardiomyopathy (ATTR-CM) patients from a pre-specified subgroup analysis of ATTRibute-CM, its Phase 3 trial of acoramidis in ATTR-CM. These data were presented at the American College of Cardiology (ACC) Annual...The serum TTR level increase with acoramidis was accompanied by a significant reduction in the risk of ACM or first CVH versus placebo in both the ATTRv-CM (59.1% risk reduction, .41 hazard ratio) and ATTRwt-CM (31.2% risk reduction, .69 hazard ratio) subgroups."

P3 data • Cardiomyopathy

Beyonttra (acoramidis), the First Near-complete TTR Stabilizer (≥90%), Approved in Japan to Treat ATTR-CM (GlobeNewswire) - "BridgeBio Pharma, Inc...announced the Japanese Ministry of Health, Labour and Welfare has approved acoramidis, under the brand name Beyonttra, for the treatment of adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM)...The approval in Japan is based on positive results from a Phase 3 open-label, single-arm study conducted in Japan by Alexion, AstraZeneca Rare Disease, and the positive results from the global ATTRibute-CM Phase 3 study....Based on the terms of the agreement, BridgeBio will receive a $30 million milestone payment upon approval in Japan, as well as royalties in the low double digits on sales of acoramidis in Japan, with commercialization efforts planned in the first half of 2025."

Japan approval • Launch non-US • Cardiomyopathy