Flyrcado Drug Information

Overview of Clinical Studies

The safety and effectiveness of FLYRCADO were evaluated in two prospective, multicenter, open-label clinical studies in adults with either suspected coronary artery disease (CAD) (Study 1: NCT03354273) or known or suspected CAD (Study 2: NCT01347710). Subjects received two injections of FLYRCADO: one at rest and one during stress . For the FLYRCADO stress injection, subjects received either a pharmacologic stress agent or engaged in exercise stress. PET myocardial perfusion imaging (MPI) was performed at both rest and stress using cardiac gating and low-dose CT attenuation correction. Subjects also received rest and stress SPECT MPI using technetium Tc 99m sestamibi or technetium Tc 99m tetrofosmin on a different day from the PET MPI. The stress modality was to be the same for PET and SPECT. Stress and rest images were displayed side-by-side for the assessment of perfusion and wall motion abnormalities.

Three qualified readers, blinded to clinical data, performed independent assessment of each subject's rest and stress images, with each recording an overall qualitative diagnosis of normal, ischemia, ischemia plus scar, or scar. For analyses of sensitivity and specificity, normal was considered image negative and all other diagnoses were considered image positive.

Suspected Coronary Artery Disease Study 1 evaluated the sensitivity and specificity of

FLYRCADO PET MPI for the detection of significant CAD in subjects with suspected CAD who were scheduled for invasive coronary angiography (ICA). A total of 578 subjects were evaluable for effectiveness, having rest and stress imaging and evaluable truth standard data. Subjects ranged in age from 26 years to 88 years, with a mean age of 64 years. A total of 188 (33%) were female, and 473 (82%) were White, 35 (6%) were Black or African American, 6 (1%) were Asian, and 64 (11%) were other races or not reported.

In addition, 79 subjects (14%) reported Hispanic/Latino ethnicity. Pharmacologic stress was performed in 83% of subjects and exercise stress in 17% of subjects. The sensitivity and specificity of FLYRCADO PET MPI for detection of significant CAD, defined as the presence of significant stenosis in at least one major epicardial coronary artery or major branch by quantitative coronary angiography (QCA) are reported in Table 6. Results for both ≥50% stenosis and a secondary analysis using ≥70% stenosis as the threshold for significant CAD are shown.

Table 6. Diagnostic Performance of FLYRCADO PET MPI in Study 1 (N = 578 Includes 12 subjects who had reference standard images categorized as uninterpretable by the central reader but were forced to be diagnosed as positive or negative (2 subjects as positive and 10 subjects as negative). ) ≥50% Stenosis Reference Standard ≥70% Stenosis Reference Standard Reader Sensitivity (95% CI) N=249 Specificity (95% CI) N=329 Sensitivity (95% CI) N=127 Specificity (95% CI) N=449 Abbreviations: CI = confidence interval, MPI = myocardial perfusion imaging Reader 1 77% (72%, 82%) 66% (61%, 71%) 91% (86%, 96%) 58% (54%, 63%) Reader 2 74% (68%, 79%) 70% (65%, 75%) 87% (82%, 93%) 62% (58%, 67%) Reader 3 89% (85%, 93%) 53% (47%, 58%) 97% (94%, 100%) 44% (39%, 49%) From a blinded re-evaluation of 60 randomly selected PET MPI images presented during the main reading sessions, intra-reader kappa ranged from 0.71 to 0.93 for the three readers. Using a 50% stenosis threshold, sensitivity of SPECT MPI was 61% to 76% for the three readers, with the lower bound of the 95% confidence intervals ranging from 55% to 70%, and specificity of SPECT MPI was 51% to 65%, with the lower bound of the 95% confidence intervals ranging from 46% to 60%.

Known or Suspected Coronary Artery Disease Study 2 evaluated the sensitivity and

specificity of FLYRCADO PET MPI for the detection of significant CAD in subjects with known or suspected CAD who had ICA without intervention within 60 days prior to imaging or were scheduled for ICA. A total of 755 subjects were evaluable for effectiveness, having rest and stress imaging for FLYRCADO PET and evaluable truth standard data. Subjects ranged in age from 36 years to 90 years, with a mean age of 63 years. A total of 235 (31%) were female, and 619 (82%) were White, 101 (13%) were Black or African American, 8 (1%) were Asian, and 24 (4%) were other races or not reported.

Pharmacologic stress was performed in 71% of subjects and exercise stress in 29% of subjects. The sensitivity and specificity of FLYRCADO PET MPI for the detection of significant CAD, defined as the presence of significant stenosis in at least one major epicardial coronary artery or major branch by QCA or as history of myocardial infarction are reported in Table 7. Results for both ≥50% stenosis and a secondary analysis using a threshold of ≥70% stenosis for significant CAD are shown. Table 7. Diagnostic Performance of FLYRCADO PET MPI in Study 2 (N = 755) ≥50% Stenosis or Confirmed MI Reference Standard ≥70% Stenosis or Confirmed MI Reference Standard Reader Sensitivity (95% CI) N=352 Specificity (95% CI) N=403 Sensitivity (95% CI) N=245 Specificity (95% CI) N=510 Abbreviations: CI = confidence interval, MI = myocardial infarction, MPI = myocardial perfusion imaging Reader 1 73% (68%, 78%) 73% (68%, 77%) 82% (77%, 87%) 68% (63%, 71%) Reader 2 63% (57%, 67%) 86% (82%, 89%) 72% (66%, 78%) 80% (77%, 83%) Reader 3 77% (72%, 80%) 66% (62%, 71%) 85% (80%, 89%) 61% (57%, 66%) From a blinded re-evaluation of a randomly selected 10% of PET MPI images presented during the main reading sessions, intra-reader agreement ranged from 90% to 95% for the three readers.

Using a 50% stenosis threshold, sensitivity of SPECT MPI was 43% to 58% for the three readers, with the lower bound of the 95% confidence intervals ranging from 38% to 53%, and specificity for SPECT MPI was 80% to 92%, with the lower bound of the 95% confidence intervals ranging from 76% to 89%.