BridgeBio doses first patient in ASCEND-ATTR Phase 3b/4 study
BridgeBio Pharma has dosed the first participant in ASCEND-ATTR, a Phase 3b/4 study designed to assess whether prolonged treatment with its approved small-molecule drug acoramidis (Attruby) can achieve sustained structural and functional cardiac improvement in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).
The single-arm, open-label, longitudinal study will enrol approximately 150 adults and follow them over 36 months using two complementary imaging modalities: cardiovascular magnetic resonance (CMR) and cardiac echocardiography, performed annually. The primary efficacy endpoint is responder status at Month 36 by CMR, based on improvement from baseline in left ventricular systolic function. Secondary endpoints capture additional CMR and echocardiographic measures of cardiac structure, function, and amyloid burden at Months 12, 24, and 36, alongside circulating biomarkers.
From slowing progression to reversing it
ASCEND-ATTR is built on signals emerging from the CMR substudy of the pivotal ATTRibute-CM trial. That analysis found that acoramidis treatment was associated with mean improvements in Left Ventricular Mass Index, Left Ventricular Stroke Volume Index, and Left Ventricular Ejection Fraction through 30 months, with evidence of amyloid regression in a subset of patients. The working hypothesis is that near-complete TTR stabilisation allows the body's endogenous amyloid clearance mechanisms to outpace ongoing amyloid formation, creating the conditions for cardiac remodelling.
Ahmad Masri of Oregon Health and Science University, a co-investigator in the study, said the ATTRibute-CM CMR substudy provided "the first real signal that TTR stabilisation can do more than slow disease progression" and that ASCEND-ATTR will enable prospective study of these changes "across a notably larger patient cohort and with two complementary imaging modalities."
BridgeBio plans to present further data from the ATTRibute-CM CMR substudy and its open-label extension, compared against a natural history cohort, at the European Society of Cardiology Congress 2026.
Competitive landscape and regulatory context
The ATTR-CM treatment market is increasingly competitive. Pfizer's tafamidis (Vyndaqel/Vyndamax), the first approved TTR stabiliser, holds the dominant commercial position after several years on market. BridgeBio differentiates acoramidis on the basis of its near-complete (90% or greater) TTR stabilisation at therapeutic doses, compared with the partial stabilisation attributed to tafamidis. Whether that pharmacological distinction translates into meaningfully superior cardiac remodelling outcomes over multi-year follow-up is precisely what ASCEND-ATTR is designed to address.
The broader ATTR-CM field is also seeing new entrants. RNA-interference and antisense approaches targeting TTR synthesis, including Alnylam's vutrisiran and Ionis's eplontersen, are approved or advancing in cardiomyopathy indications. These agents operate by reducing TTR production rather than stabilising the protein, and some investigators believe a combination approach may ultimately be warranted. ASCEND-ATTR does not include a combination arm, but its imaging endpoints and biomarker data could inform future study designs across the class.
For BridgeBio, the initiation of ASCEND-ATTR represents a post-approval commitment to generating evidence beyond cardiovascular mortality and hospitalisation rates, the endpoints that underpinned Attruby's FDA approval. Demonstrating durable, measurable cardiac remodelling would strengthen the drug's label narrative and commercial position at a time when ATTR-CM is attracting growing diagnostic attention as awareness improves and non-invasive diagnostic tools become more widely used.