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Hosts explore the latest advancements in amyloidosis treatment, with expert insights on emerging therapies and patient care strategies.
00:00:00 Introduction and Guest Introduction
00:00:52 Current State of Amyloid Therapeutics
00:03:41 Introduction of New Stabilizers and Silencers
00:06:05 Combination Therapy and Clinical Data
00:10:36 Choosing Therapy for Patients
00:16:40 Disease Progression and Clinical Trials
00:20:28 Pipeline and Future Therapies
00:23:51 Preventative Therapy and Asymptomatic Patients
00:27:19 Conclusion and Future Directions
This episode of Don’t Miss a Beat centers on the evolving treatment landscape for transthyretin amyloid cardiomyopathy (ATTR-CM) with special guest Ahmad Masri, MD. Hosts Muthiah Vaduganathan, MD, MPH, a cardiologist and codirector of the Center for Cardiometabolic Implementation Science at Brigham and Women’s Hospital, and Steve Greene, MD, an advanced heart failure specialist at Duke University School of Medicine, are joined by Masri, who serves as the director of the HCM and Amyloid Program at Oregon Health & Science University, to discuss the rapid therapeutic advances in ATTR-CM and the emerging questions shaping real-world clinical practice.
Masri reviews the progression from a previously untreatable disease to one now managed with three US Food and Drug Administration (FDA)-approved disease-modifying agents: tafamidis (VYNDAMAX), acoramidis (Attruby), and vutrisiran (AMVUTTRA).1,2,3
He highlights the tafamidis approval in 2019 as a landmark in the field, showing a substantial survival benefit in the ATTR-ACT trial, followed by similar results from acoramidis, which received approval in late 2024, in ATTRibute-CM.1,2
Vutrisiran, a TTR gene silencer approved by the FDA in March 2025, represents a mechanistically distinct approach validated in the HELIOS-B trial.3 Despite these advances, Masri notes that patients with late-stage disease derive limited symptomatic benefit and that residual risk remains high, even with treatment.
The conversation explores whether stabilizers and silencers can or should be combined, with Masri urging caution, citing the absence of clinical data demonstrating additive benefit and warning against assumptions of harmony without clinical evidence. Masri indicated ongoing trials, such as CARDIO-TTRansform, may offer clarity on this issue.4
Without direct comparisons between therapies, treatment selection often hinges on patient preference, delivery method, pill burden, and payer coverage. In practice, clinicians rely on pharmacodynamic markers, like changes in TTR levels, to assess treatment effect and adjust therapy accordingly. Masri emphasizes that while ATTR-CM trials may not show improvements in quality-of-life scores, slowing disease progression remains a critical and meaningful endpoint in this severe, high-mortality condition.
Looking ahead, the panel discusses the next wave of therapeutic innovation. Multiple trials are now testing agents that aim to clear amyloid from the myocardium, including NI006 (ALXN2220), PRX004, and AT-02.5,6,7 These immune-modulating treatments are designed for long-term use and may complement stabilizers or silencers in patients with established amyloid burden.
The episode closes with a discussion on prevention. For patients with asymptomatic cardiac involvement, current therapies halt disease progression entirely in many cases. For those with pathogenic TTR variants but no overt disease, surveillance is the current standard. However, Masri introduces the ACT-EARLY trial, which will test whether early treatment with acoramidis can prevent the onset of clinical disease in high-risk individuals, potentially reshaping the paradigm of ATTR-CM care.8
Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for Greene include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others.
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