Development

Bayer's iodine 124 evuzamitide meets primary endpoints in Phase III cardiac amyloidosis imaging trial

Bayer has reported that iodine 124 evuzamitide met both primary endpoints in the Phase III REVEAL study, demonstrating sufficient sensitivity and specificity for cardiac amyloidosis PET imaging by visual scan interpretation — results that could support the first FDA-approved diagnostic agent specifically labeled for the condition.

The long-standing diagnostic need

Cardiac amyloidosis is caused by the accumulation of misfolded proteins in heart tissue, progressively impairing cardiac function and leading to heart failure, frequent hospitalization, and early mortality. Despite growing clinical awareness, the disease carries a diagnostic delay of roughly two to four years from symptom onset, with patients typically consulting multiple specialists and undergoing several imaging procedures before receiving an accurate diagnosis.

The core problem is structural: no single non-invasive test currently holds FDA approval for reliably detecting cardiac amyloidosis. The dominant clinical tool — technetium-99m pyrophosphate (99mTc-PYP) scintigraphy — is used entirely off-label for this purpose. Its clinical utility is also constrained by a fundamental limitation: it detects transthyretin amyloidosis (ATTR) selectively but performs poorly in light-chain amyloidosis (AL), the second major subtype. Patients with AL cardiac involvement must often proceed to endomyocardial biopsy or rely on indirect diagnostic pathways.

It is within this landscape that Bayer's radiotracer cardiac amyloidosis program, built around iodine 124 evuzamitide, is advancing.

What the REVEAL study measured

The REVEAL study is a multicenter, open-label, single-arm Phase III trial conducted at 19 centers across the United States. It enrolled 170 adults with suspected cardiac amyloidosis and was sponsored by Brigham and Women's Hospital in Boston as an investigator-initiated study. Participants received a single intravenous dose of I-124 evuzamitide, followed by PET/CT cardiac and partial-body imaging three to five hours post-injection.

The primary endpoints were diagnostic sensitivity — the ability to correctly identify patients who have cardiac amyloidosis — and specificity — the ability to correctly identify those who do not. Both were assessed by visual PET/CT scan interpretation, with standard-of-care diagnosis serving as the reference standard. That reference diagnosis was adjudicated independently by clinical amyloidosis experts blinded to PET results, using routine diagnostic data collected up to 60 days after imaging. PET images were read by experienced cardiac PET physicians blinded to clinical data.

Bayer announced that both primary endpoints were met. The company has not yet disclosed the numerical sensitivity and specificity values, stating that complete results will be presented at an upcoming scientific congress.

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Molecule and mechanism

I-124 evuzamitide — also known as AT-01 and, in the scientific literature, as 124I-p5+14 — is a radiolabeled synthetic peptide that binds to extracellular amyloid deposits, including amyloid fibrils and associated glycosaminoglycans. Unlike 99mTc-PYP, which exploits a calcium-mediated binding mechanism that is selective for ATTR-type amyloid, evuzamitide's p5+14 peptide scaffold binds amyloid fibrils across subtypes, making it a pan-amyloid agent capable of detecting both ATTR and AL cardiac involvement with a single scan.

This pan-amyloid coverage is clinically relevant. A 2023 case report published in the Journal of Nuclear Cardiology described a patient with hereditary cardiac amyloidosis in whom 124I-AT-01 PET identified disease when both cardiac MRI and 99mTc-PYP SPECT scintigraphy were negative. That is a single case and cannot be generalized, but it illustrates the potential diagnostic reach of PET/CT cardiac amyloidosis imaging with a pan-amyloid tracer in cases where existing tools fall short.

Beyond initial diagnosis, the quantitative nature of PET/CT imaging creates a potential role for evuzamitide in monitoring amyloid burden over time — a capability that current SPECT-based approaches cannot reliably provide.

I-124 evuzamitide was originally developed by Attralus, Inc., which received FDA Breakthrough Therapy Designation for the compound in August 2024 for PET imaging in patients with suspected or known cardiac amyloidosis. Orphan Drug status was previously granted in both the US and EU for AL and ATTR amyloidosis. Bayer acquired the compound from Attralus in early 2026 as part of a transaction that also brought a second investigational amyloid radiotracer into its radiology pipeline.

Bayer has stated it plans to discuss the REVEAL data and a regulatory submission pathway with the FDA and other health authorities. No submission timeline has been disclosed. The full REVEAL dataset will also be presented at an upcoming scientific congress, at which point the numerical sensitivity and specificity results, along with subtype-specific secondary analyses and safety data, will be available for independent evaluation.


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