At the Heart Failure Society of America annual meeting, researchers presented phase III REVEAL study data showing that the investigational radiotracer 124I-evuzamitide PET/CT achieved 93.5% sensitivity and 86.0% specificity in detecting cardiac amyloidosis. The test outperformed bone scintigraphy in identifying early-stage transthyretin disease (93% vs 68%), enabling timely intervention with therapies like tafamidis. Based on the results, Bayer plans to submit 124I-evuzamitide for regulatory approval.
Evuzamitide PET/CT diagnostic performance
- ▪In the phase III REVEAL study, 124I-evuzamitide PET/CT achieved a sensitivity of 93.5%, specificity of 86.0%, negative predictive value of 94.1%, and positive predictive value of 84.7% for identifying cardiac amyloidosis.
- ▪124I-evuzamitide PET/CT demonstrated similar diagnostic performance for identifying light-chain (AL) amyloidosis and transthyretin amyloidosis (ATTR).
- ▪Quantitative cardiac uptake of 124I-evuzamitide aligned with transthyretin amyloidosis (ATTR) burden across NT-proBNP, troponin, global longitudinal strain, and left ventricular wall thickness metrics.
- ▪Bayer plans to submit 124I-evuzamitide for regulatory approval based on the phase III REVEAL trial results.
Early cardiac amyloidosis detection
- ▪124I-evuzamitide PET/CT detected early transthyretin amyloidosis in patients with left ventricular wall thickness under 12 mm (100%) and under 13 mm (95%).
- ▪In a post hoc analysis of the REVEAL study, 44% of subjects with PET-detected transthyretin amyloidosis had early-stage disease.
- ▪124I-evuzamitide PET/CT detected early, low-burden transthyretin amyloidosis in patients with NT-proBNP levels under 350 ng/L (89%) and under 600 ng/L (92%).
- ▪Eight REVEAL trial participants who tested negative for transthyretin amyloidosis on bone scintigraphy were identified as positive via 124I-evuzamitide PET imaging and initiated therapy.
REVEAL study patient population
- ▪The prospective phase III REVEAL study evaluated 124I-evuzamitide PET/CT across 18 U.S. centers in patients with suspected cardiac amyloidosis, who had a median age of 72 years and were 75% men.
- ▪In the REVEAL study cohort of patients with suspected cardiac amyloidosis, over 75% of participants were in New York Heart Association functional class I or II.
- ▪Clinical adjudicators in the REVEAL study identified 54 participants with transthyretin amyloidosis and 21 participants with light-chain amyloidosis out of the screened cohort.
- ▪REVEAL trial participants received a 1 mCi dose of 124I-evuzamitide PET/CT along with three days of oral potassium iodide to block thyroid iodine uptake.
Evuzamitide binding mechanism
- ▪Amyloid tissue deposits throughout the body consist of amyloid fibrils, glycosaminoglycans, and proteins that carry positive charges.
- ▪124I-evuzamitide is a 45-amino-acid peptide heavily laden with lysine residues that carries negative charges designed to bind to amyloid deposits.
- ▪Labeling the evuzamitide peptide with radioactive iodine-124 enables noninvasive identification and quantitative measurement of amyloid deposits in organs including the heart.
Bone scintigraphy comparison
- ▪No patient with transthyretin cardiac amyloidosis detected by bone scintigraphy was missed by 124I-evuzamitide PET in the REVEAL study.
- ▪Radionuclide imaging using bone-avid radiotracers produces false negatives for early cardiac amyloidosis due to reduced sensitivity in early disease stages.
- ▪124I-evuzamitide PET/CT outperformed bone scintigraphy in detecting early transthyretin cardiac amyloidosis, achieving 93% sensitivity compared to 68% for bone scintigraphy (P=0.016).
Available cardiac amyloidosis treatments
- ▪Currently approved cardiac amyloidosis therapies prevent new amyloid deposits from forming but do not clear pre-existing latent amyloid from the myocardium.
- ▪Eplontersen failed to show a cardiovascular outcome benefit in the CARDIO-TTRansform phase III trial for transthyretin cardiac amyloidosis.
- ▪Current available transthyretin cardiac amyloidosis treatments include the stabilizers tafamidis and acoramidis, as well as the gene silencer vutrisiran.
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