Pan-Amyloid Radiotracer Excels At Early Cardiac Amyloidosis Detection

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In the phase III REVEAL study, investigational 124I-evuzamitide PET/CT detected cardiac amyloidosis with 93.5% sensitivity and identified early transthyretin disease more often than bone scintigraphy. Bayer said it plans to submit the tracer for regulatory review, but the study was relatively small, had short follow-up and does not establish how the scan will perform in routine practice.

An investigational PET/CT tracer detected cardiac amyloidosis with 93.5% sensitivity in the phase III REVEAL study and identified early transthyretin amyloidosis (ATTR) more often than bone scintigraphy, according to results presented at the Heart Failure Society of America annual meeting. Bayer said it plans to submit 124I-evuzamitide for regulatory review, although its performance in routine care and the timing of any submission remain unknown.

Among 170 people evaluated for suspected cardiac amyloidosis, the tracer had 86.0% specificity, a negative predictive value of 94.1% and a positive predictive value of 84.7%. It performed similarly in identifying light-chain (AL) amyloidosis and ATTR, reported study presenter Mathew Maurer, MD, of Columbia University Irving Medical Center. The results were based on PET/CT scans interpreted by three readers blinded to other clinical information, compared with diagnoses determined by amyloidosis experts who did not see the scans.

For early ATTR, evuzamitide PET detected disease more often than bone scintigraphy: 93% versus 68% (P=0.016). The difference was also seen in groups with lower NT-proBNP levels and less pronounced heart-wall thickening. For example, among participants with left ventricular wall thickness below 12 mm, detection was 100% with PET and 78% with bone scintigraphy. These subgroup results suggest potential value in patients whose disease may be harder to identify with existing imaging.

Of the 170 participants, 54 were found to have ATTR and 21 had AL amyloidosis. PET detected ATTR across bone-scan grades, including cases with equivocal or negative bone scans; investigators reported that no case detected by bone scintigraphy was missed by evuzamitide PET. In a post hoc analysis, 44% of participants with PET-detected ATTR met the study’s definition of early disease, based on NT-proBNP below 350 ng/L or wall thickness below 12 mm. The study also reported an acceptable safety profile from assessments on days 5 and 30.

Earlier Detection Beyond Bone Scans

Cardiac amyloidosis occurs when amyloid proteins build up in the heart, and the two forms examined in REVEAL—ATTR and AL amyloidosis—can require different clinical approaches. Finding disease before substantial cardiac changes develop could help clinicians identify patients who need further evaluation and consideration of available treatments. The study’s reported advantage in early ATTR matters because conventional bone-avid tracer scans can miss some early cases.

The findings also raise the possibility that a single imaging test could help detect both major forms and estimate the amount of amyloid in the heart. Maurer said tracer uptake tracked with measures including NT-proBNP, troponin, heart-wall thickness and global longitudinal strain. If validated, quantitative scans might help clinicians follow disease burden over time. However, REVEAL did not establish that scan-guided care improves outcomes or that changes in uptake reliably measure treatment response.

The potential benefit is not yet a replacement for established diagnostic pathways. A scan result must be interpreted alongside clinical findings and other tests, and the study’s authors noted limitations in its diagnostic reference standard. The results support further evaluation of evuzamitide; they do not by themselves show that the tracer is approved, available, or suitable for every patient.

Limits of Current Imaging

Current evaluation for suspected cardiac amyloidosis often includes radionuclide imaging with bone-avid tracers, particularly when ATTR is suspected. The report says these scans can produce false negatives in early disease. When suspicion remains high despite a negative or equivocal scan, clinicians may need additional testing, including biopsy, to establish a diagnosis.

REVEAL was a prospective, single-arm study at 18 U.S. centers. Participants received PET/CT with 1 mCi of 124I-evuzamitide and oral potassium iodide for three days to block iodine’s effects on the thyroid. The cohort’s median age was 72, 75.3% were men, and more than three-quarters were in New York Heart Association class I or II. The study compared the investigational scan with bone scintigraphy and a clinical diagnostic assessment, rather than testing whether use of the tracer changed treatment or patient outcomes.

Potential treatment options for ATTR have expanded, including transthyretin stabilizers and a gene-silencing therapy, as well as other candidates in development. That makes timely diagnosis a practical concern, but treatment decisions depend on the confirmed disease type and individual clinical assessment. The report also notes that heightened clinical suspicion remains important: imaging cannot identify a condition that is not considered during evaluation.

“We’ve made tremendous advances on the therapeutic side.”

— Mathew Maurer, MD, Columbia University Irving Medical Center

Questions Before Routine Use

REVEAL included 170 participants and only 21 with AL amyloidosis, limiting the strength of conclusions for that subtype. Follow-up was 60 days, which Maurer acknowledged is short. The investigators also relied on available clinical records to establish the reference diagnosis, a constraint that could affect comparisons with the scan.

The study does not establish how well evuzamitide will perform across a broader real-world population, whether its quantitative measurements can track treatment effects, or whether using it will improve clinical outcomes. The source report does not give a submission date, regulatory decision timeline, or details of a planned confirmatory study. The reported test characteristics also reflect this study’s participants and diagnostic approach and may not apply unchanged to other settings.

Regulatory Review and Further Evidence

Bayer said it plans to submit 124I-evuzamitide for regulatory approval. The company has not, in the reported information, specified when it will file or when regulators might act. Any decision will depend on review of the study data and the applicable regulatory process; the tracer remains investigational in the source report.

Further data will be needed to clarify performance in larger and more varied patient groups, especially people with AL amyloidosis and patients with early or inconclusive findings on existing scans. Researchers and clinicians will also need evidence on how PET results affect diagnosis, treatment decisions and outcomes, and whether repeat scans can meaningfully track amyloid burden. Until then, the findings are promising study results rather than confirmation of routine clinical benefit.

Key Questions

What is 124I-evuzamitide?

It is an investigational radiotracer used with PET/CT to detect and quantify amyloid in the heart. The report says it is not yet approved and that Bayer plans to submit it for regulatory review.

How did the tracer perform in REVEAL?

In the 170-person study, reported sensitivity was 93.5% and specificity was 86.0%. Its negative and positive predictive values were 94.1% and 84.7%, respectively; these figures reflect the study population and its diagnostic methods.

Was it better than bone scintigraphy?

For early ATTR in the study, evuzamitide PET detected disease in 93% of cases, compared with 68% for bone scintigraphy. The report also describes PET-positive cases with equivocal or negative bone scans, but further evidence is needed to determine performance in routine practice.

Can the scan show whether treatment is working?

The researchers found that tracer uptake corresponded with several measures of disease burden, suggesting a possible role in monitoring. REVEAL did not establish that changes in uptake reliably show treatment response or improve patient outcomes.

When could the scan become available?

Bayer said it plans to seek regulatory approval, but the report gives no filing date or decision timeline. The tracer remains investigational pending regulatory review.

Source: rss