The phase I/II trial of AT-01, a radiotracer for amyloidosis deposits

On April 4, 2020, new data were released for a phase I/II trial (NCT03678259) investigating the ability of iodine-124 evuzamitide (AT-01) to detect amyloid deposits by positron emission tomography/computed tomography (PET/CT) imaging in patients with systemic amyloidosis.¹

AT-01 is a first-in-class pan-amyloid binding peptide, which is being investigated as a radiotracer for the diagnosis of systemic amyloidosis. It can detect diverse types of amyloid deposits, including immunoglobulin light-chain-associated (AL) amyloidosis and transthyretin-associated amyloidosis (ATTR), in major organs (e.g., heart, kidney, liver, and spleen).¹

Study design¹

• A phase I/II trial to investigate the ability of AT-01 to detect amyloid deposits by PET/CT imaging in patients with diverse forms of systemic amyloidosis.
• Enrolment included patients with
  • AL amyloidosis (n = 25);
  • ATTR amyloidosis (n = 20);
  • asymptomatic transthyretin variant (TTRv; n = 2);
  • patients with amyloidosis caused by either leukocyte cell-derived chemotaxin-2 (ALECT2), gelsolin (AGel), lysozyme (ALys), or apolipoprotein A-1 (AapoA1) (n = 5);
  • and healthy controls (n = 5).
• Intravenous infusion of <2 mg AT-01 (≤2 mCi) was administered to all patients and images were acquired 5–6 hours postinjection using a Biograph PET/CT with a low-dose CT.
• Efficacy endpoints: patient- and organ-based sensitivity of AT-01 uptake in the heart, liver, spleen, and kidney.

Results¹

• Cardiac uptake was seen in 16/25 patients with AL amyloidosis and 17/20 patients with ATTR amyloidosis.
  • Cardiac uptake was also seen in 11 patients who had not previously been diagnosed, including those with ATTR amyloidosis with normal N-terminal pro B-type natriuretic peptide (NT-proBNP), or negative or equivocal pyrophosphate scintigraphy scores.
• In patients with previously diagnosed cardiac amyloidosis, sensitivity was 93% (13/14) for those with AL amyloidosis and 100% (11/11) for those with ATTR amyloidosis.
• As expected, AT-01 was not seen in the heart of the five healthy controls.
• Retention of AT-01 in the heart correlated significantly with serum NT-proBNP in patients with AL amyloidosis, in which NT-proBNP has been validated as a surrogate for survival.
• Automated three-dimensional standardized uptake value ratio (3DSUVR) mean and manual two-dimensional SUVR mean yielded excellent positive correlations for the heart, with rp = 0.93 and p < 0.0001.

Systemic amyloidosis is a significantly underdiagnosed disease due to low awareness, lack of specific symptoms, and no current disease-specific diagnostic tools. AT-01 could potentially be a key tool for the detection of early cardiac deposits and to quantify amyloid burden for a diverse range of patients with amyloidosis.