Drug Trials Snapshots: FLYRCADO
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the FLYRCADO Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
FLYRCADO (Flurpiridaz F 18 Injection)
(Fleer-CAH-doe)
GE Healthcare Inc.
Approval date: September 27, 2024
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
FLYRCADO is a drug used to image the supply of blood to portions of the heart muscle tissue in adult patients who have known or suspected disease of the coronary arteries, which deliver blood to the heart muscle.
How is this drug used?
FLYRCADO is an injection given by a health care provider in the vein (intravenous). It is usually given twice, once at rest and once during stress that increases blood delivery to the heart muscle. The stress can be caused by exercise or certain drugs. After each dose of FLYRCADO, imaging of the heart is done using positron emission tomography (also called a PET scan). The images are evaluated to find parts of the heart muscle that have lower supply of blood.
Who participated in the clinical trials?
Evidence of effectiveness of FLYRCADO was primarily provided by two clinical trials (Trial 1: NCT03354273 and Trial 2: NCT01347710) of 1333 evaluable patients with either suspected coronary artery disease (CAD) (Trial 1, 578 patients) or known or suspected CAD (Trial 2, 755 patients). Trial 1 was conducted at 48 sites in the United States, Canada, Finland, France, Germany, and the Netherlands, and Trial 2 was conducted at 76 sites in the United States, Canada, and Finland.
The safety of FLYRCADO was evaluated in 1600 patients who received either 1 or 2 (rest and stress) doses of FLYRCADO. The number of patients representing efficacy findings differs from the number of patients representing safety findings due to different pools of study participants analyzed for efficacy and safety.
How were the trials designed?
The safety and effectiveness of FLYRCADO were evaluated in two trials in adults with either suspected CAD or known or suspected CAD. Patients received two injections of FLYRCADO: one at rest and one during stress. For the FLYRCADO stress injection, patients received either a stress drug or exercised. PET myocardial perfusion imaging (MPI) was performed at both rest and stress.
Stress and rest images were evaluated by three qualified readers, blinded to clinical data, who independently recorded an overall diagnosis of normal or decreased blood supply to the heart muscle. These results were compared with invasive coronary angiography, which can detect narrowing or blockage of the coronary arteries.
How were the trials designed?
The safety and effectiveness of FLYRCADO were evaluated in two prospective, multicenter, open-label clinical trials in adults with either suspected CAD or known or suspected CAD.
Patients received two injections of FLYRCADO: one at rest and one during stress. For the FLYRCADO stress injection, patients 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.
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.
Trial 1 evaluated the sensitivity and specificity of FLYRCADO PET MPI for the detection of significant CAD in patients 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 (≥50%) stenosis in at least one major epicardial coronary artery or major branch by quantitative coronary angiography (QCA) were reported.
Trial 2 evaluated the sensitivity and specificity of FLYRCADO PET MPI for the detection of significant CAD in patients 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 (≥50%) stenosis in at least one major epicardial coronary artery or major branch by QCA or as history of myocardial infarction (MI) were reported.
DEMOGRAPHICS SNAPSHOT
Figure 1 summarizes how many male and female patients were enrolled in the clinical trials used to evaluate the efficacy of FLYRCADO.
Figure 1. Baseline Demographics by Sex (mITT Population)
Source: Adapted from FDA Review
Abbreviations: mITT, modified intent-to-treat
Figure 2 summarizes how many patients by race were enrolled in the clinical trials used to evaluate the efficacy of FLYRCADO.
Figure 2. Baseline Demographics by Race (mITT Population)
Source: Adapted from FDA Review
Abbreviations: mITT, modified intent-to-treat
Figure 3 summarizes how many patients by age were enrolled in the clinical trials used to evaluate the efficacy of FLYRCADO.
Figure 3. Baseline Demographics by Age (mITT Population)
Source: Adapted from FDA Review
Abbreviations: mITT, modified intent-to-treat
Figure 4 summarizes how many patients by ethnicity were enrolled in the clinical trials used to evaluate the efficacy of FLYRCADO.
Figure 4. Baseline Demographics by Ethnicity (mITT Population)
Source: Adapted from FDA Review
Abbreviations: mITT, modified intent-to-treat
Who participated in the trials?
Table 1. Baseline Demographics of Patients in the Clinical Trials (mITT Population)
| Demographic | Pooled Set N=1333 | Trial 1 N=578 | Trial 2 N=755 |
|---|---|---|---|
| Age, years | |||
| Mean (SD) | 62.9 (9.5) | 63.7 (9.5) | 62.3 (9.5) |
| Median (min, max) | 64 (26, 90) | 64 (26, 88) | 63 (36, 90) |
| Age group, years, n (%) | |||
| <65 | 725 (54) | 295 (51) | 430 (57) |
| ≥65 | 608 (46) | 283 (49) | 325 (43) |
| Sex, n (%) | |||
| Male | 910 (68) | 390 (67) | 520 (69) |
| Female | 423 (32) | 188 (33) | 235 (31) |
| Race, n (%) | |||
| American Indian or Alaska Native | 3 (<1) | 1 (<1) | 2 (<1) |
| Asian | 14 (1) | 6 (1) | 8 (1) |
| Black or African American | 136 (10) | 35 (6) | 101 (13) |
| Native Hawaiian or Pacific Islander | 7 (<1) | 3 (1) | 4 (<1) |
| White or Caucasian | 1092 (82) | 473 (82) | 619 (82) |
| Not Reported | 60 (5) | 57 (10) | 3 (<1) |
| Other | 21 (2) | 3(1) | 18 (2) |
| Ethnicity, n (%) | |||
| Hispanic | 118 (9) | 79 (14) | 39 (5) |
| Non-Hispanic | 1078 (81) | 405 (70) | 673 (89) |
| Missing | 1 (<1) | 1 (<1) | 0 |
| Not Reported | 136 (10) | 93 (16) | 43 (6) |
Source: Adapted from FDA Review
Abbreviations: mITT, modified intent-to-treat; SD, standard deviation
What are the benefits of this drug?
In Trial 1, among the 249 patients considered positive for significant CAD, FLYRCADO PET MPI imaging showed positive results for 74% to 89% of patients by the three readers, and among the 329 patients considered negative for significant CAD, FLYRCADO PET MPI imaging showed negative results for 53% to 70% of patients by the three readers.
In Trial 2, among the 352 patients considered positive for significant CAD, FLYRCADO PET MPI imaging showed positive results for 63% to 77% of patients by the three readers, and among the 403 patients considered negative for significant CAD, FLYRCADO PET MPI imaging showed negative results from 66% to 86% of patients by the three readers.
What are the benefits of this drug (results of trials used to assess efficacy)?
Trial 1 evaluated the sensitivity and specificity of FLYRCADO PET MPI for the detection of significant CAD in patients with suspected CAD who were scheduled for invasive coronary angiography.
Trial 2 evaluated the sensitivity and specificity of FLYRCADO PET MPI for the detection of significant CAD in patients with known or suspected CAD who had ICA without intervention within 60 days prior to imaging or were scheduled for ICA.
Table 2 shows the sensitivity and specificity of FLYRCADO PET MPI for the detection of significant CAD defined as
- presence of significant (≥50%) stenosis in at least one major epicardial coronary artery or major branch by QCA in Trial 1, and
- presence of significant (≥50%) stenosis in at least one major epicardial coronary artery or major branch by QCA or as history of myocardial infarction in Trial 2.
Table 2. Diagnostic Performance of FLYRCADO PET MPI (mITT Populations)
| Trial 1 (N=578) | Trial 2 (N=755) | |||
|---|---|---|---|---|
| Reader | Sensitivity % (95% CI) N = 249 | Specificity % (95% CI) N=329 | Sensitivity % (95% CI) N = 352 | Specificity % (95% CI) N=403 |
| Reader 1 | 77 (72, 82) | 66 (61, 71) | 73 (68, 78) | 73 (68, 77) |
| Reader 2 | 74 (68, 79) | 70 (65, 75) | 63 (57, 67) | 86 (82, 89) |
| Reader 3 | 89 (85, 93) | 53 (47, 58) | 77 (72, 80) | 66 (62, 71) |
Source: FLYRCADO Prescribing Information
Note: The readers are different for the two trials.
Abbreviations: mITT, modified intent-to-treat; CI, confidence interval.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: In Trial 1, the sensitivity and specificity of FLYRCADO were numerically higher in females than males for all readers. In Trial 2, the sensitivity of FLYRCADO was numerically lower while the observed specificity of FLYRCADO was numerically higher in females than males for all readers. However, these observations are not considered clinically meaningful.
- Race: The number of patients of races other than White was small; therefore, differences in how FLYRCADO worked among races could not be determined.
- Age: In Trial 1, the sensitivity of FLYRCADO was similar in patients below and above 65 years of age for all readers and the specificity of FLYRCADO was numerically higher in patients below 65 years of age for all readers. In Trial 2, the sensitivity and specificity of FLYRCADO were numerically higher in patients below 65 years of age for all readers. However, the observations are not expected to have meaningful clinical impact.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Table 3. Efficacy Results by Sex, Age, and Race (mITT Populations)
| Trial 1 (N=578) | Trial 2 (N=755) | ||||
|---|---|---|---|---|---|
| Parameter | Reader | Sensitivity % (95% CI) N=249 | Specificity % (95% CI) N=329 | Sensitivity % (95% CI) N=352 | Specificity % (95% CI) N=403 |
| Sex | |||||
| Male | N=208 | N=182 | N=293 | N=227 | |
| Reader 1 | 76 (70, 82) | 60 (53, 67) | 75 (70, 80) | 69 (63, 75) | |
| Reader 2 | 73 (67, 79) | 65 (58, 72) | 64 (59, 69) | 85 (79, 89) | |
| Reader 3 | 88 (84, 92) | 47 (40, 55) | 78 (73, 83) | 62 (56, 68) | |
| Female | N=41 | N=147 | N=59 | N=176 | |
| Reader 1 | 83 (71, 94) | 73 (66, 80) | 64 (52, 75) | 77 (71, 83) | |
| Reader 2 | 78 (65, 91) | 76 (69, 83) | 54 (42, 66) | 87 (81, 91) | |
| Reader 3 | 93 (85, 100) | 59 (51, 67) | 70 (57, 80) | 72 (65, 78) | |
| Age, years | |||||
| <65 | N=117 | N=178 | N=178 | N=252 | |
| Reader 1 | 80 (72, 87) | 69 (62, 76) | 77 (70, 83) | 74 (69, 79) | |
| Reader 2 | 73 (65, 81) | 74 (67, 80) | 69 (62, 75) | 87 (82, 91) | |
| Reader 3 | 92 (86, 97) | 57 (50, 64) | 81 (75, 86) | 68 (62, 73) | |
| ≥65 | N=132 | N=151 | N=174 | N=151 | |
| Reader 1 | 75 (68, 82) | 62 (54, 70) | 70 (62, 76) | 70 (63, 77) | |
| Reader 2 | 74 (67, 82) | 65 (57, 73) | 56 (48, 63) | 83 (77, 89) | |
| Reader 3 | 86 (81, 92) | 48 (40, 56) | 72 (65, 79) | 64 (56, 71) | |
| Race* | |||||
| White | N=207 | N=266 | N=297 | N=322 | |
| Reader 1 | 76 (70, 82) | 67 (61, 72) | 71 (66, 76) | 72 (67, 77) | |
| Reader 2 | 72 (66, 78) | 71 (66, 77) | 61 (56, 67) | 87 (83, 90) | |
| Reader 3 | 89 (85, 94) | 54 (48, 60) | 75 (70, 80) | 66 (61, 71) | |
| Black/African | N=4 | N=31 | N=42 | N=59 | |
| American | Reader 1 | 100 (40, 100) | 65 (48, 81) | 83 (69, 92) | 71 (59, 81) |
| Reader 2 | 75 (33, 100) | 65 (48, 81) | 69 (54, 81) | 78 (66, 87) | |
| Reader 3 | 100 (40, 100) | 55 (37, 72) | 83 (69, 92) | 64 (52, 75) | |
| Asian | N=4 | N=2 | - | - | |
| Reader 1 | 75 (33, 100) | 100 (16, 100) | - | - | |
| Reader 2 | 75 (33, 100) | 100 (16, 100) | - | - | |
| Reader 3 | 100 (40, 100) | 100 (16, 100) | - | - | |
| Others# | N=4 | N=3 | N=13 | N=22 | |
| Reader 1 | 100 (40, 100) | 100 (29, 100) | 85 (58, 96) | 86 (67, 95) | |
| Reader 2 | 100 (40, 100) | 100 (29, 100) | 69 (42, 87) | 91 (72, 98) | |
| Reader 3 | 100 (40, 100) | 67 (13, 100) | 92 (67, 99) | 73 (52, 87) | |
Source: Adapted from FDA Review
* Race: The number of patients other than White was small; therefore, differences in how FLYRCADO worked among races could not be determined.
#Others: Trial 1 included 1 American Indian or Alaska Native, 3 Native Hawaiian or Pacific Islander, and 3 other, excluding 57 not reported. Trial 2 included 8 Asian, 2 American Indian or Alaska Native, 4 Native Hawaiian or Pacific Islander, 3 not reported, and 18 other.
Note: The readers were different for the two trials. The 95% confidence intervals are computed using Clopper-Pearson exact interval estimates for 100% proportion point estimates.
Abbreviations: mITT, modified intent-to-treat; CI, confidence interval.
What are the possible side effects?
The most commonly reported side effects, occurring in at least 10% of patients, were shortness of breath, headache, and angina pectoris/chest pain. However, it was often not possible to determine whether FLYRCADO, the associated stress procedure, or changes in baseline patient symptoms caused these reactions.
What are the possible side effects (results of trials used to assess safety)?
The safety of FLYRCADO was evaluated in 1,600 subjects in clinical studies, including 1,575 (98%) subjects with known or suspected coronary artery disease and 25 (2%) healthy subjects. All 1,600 subjects were dosed under rest conditions, with a mean dose of 102 MBq (2.8 mCi) FLYRCADO. A total of 1,568 (98%) subjects were also dosed under stress (exercise or pharmacologic) conditions, with a mean activity of 252 MBq (6.8 mCi) FLYRCADO by intravenous route. The demographic characteristics of the study population were 31% female, mean age 62 years (range 19 years to 90 years), 81% White, 11% Black or African American, 1% Asian, and 7% other or unreported race, and 10% Hispanic or Latino, 81% Not Hispanic or Latino, and 9% unreported ethnicity.
Adverse reactions occurring in ≥2% subjects receiving FLYRCARDO during PET MPI under rest and stress are presented in Table 4. Adverse reactions occurring during FLYRCADO PET MPI under rest and stress (pharmacologic or exercise) in <2% of subjects included diarrhea, palpitations, back pain, cardiac conduction disturbance, rash, dysgeusia, cough, hypotension, anxiety, vomiting, pruritus, bronchospasm, dry mouth, blood pressure elevation, syncope, and wheezing.
Table 4. Adverse Reactions Reported in ≥2% of Subjects During FLYRCADO PET MPI Under Rest and Stress (Pharmacologic or Exercise)
| Adverse Reaction | FLYRCADO PET MPI Under Rest and Stress (Pharmacologic or Exercise) N=1,600* % |
|---|---|
| Dyspnea | 17 |
| Headache | 15 |
| Angina pectoris | 10 |
| Chest pain | 8 |
| Fatigue | 7 |
| ST segment changes | 6 |
| Flushing | 5 |
| Nausea | 4 |
| Abdominal pain | 4 |
| Dizziness | 4 |
| Arrhythmia | 4 |
*Includes 32 subjects who received only one dose at rest.
Were there any differences in side effects among sex, race and age?
- Sex: In the clinical trials, the percentage of patients who experienced side effects was somewhat higher among women (57%) than among men (47%).
- Race: Because most of the participants in the safety analysis were White, differences between races in the occurrence of side effects could not be determined.
- Age: In the clinical trials, patients 65 years or older were slightly more likely to have side effects than those less than 65 years (53% vs. 47%).
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Table 5. Rate of Adverse Reactions by Age, Sex, Race, and Ethnicity (Safety Population, n=1600)
| Patients, n (%) | Patients with Any Adverse Reaction, n (%) | |
|---|---|---|
| Age | ||
| Age <65 | 880 (55) | 413 (47) |
| Age ≥65 | 720 (45) | 382 (53) |
| Sex | ||
| Male | 1107 (69) | 515 (47) |
| Female | 493 (31) | 280 (57) |
| Race | ||
| White | 1295 (81) | 668 (52) |
| Black or African American | 169 (11) | 81 (48) |
| Asian | 21 (1) | 0 (0) |
| Native Hawaiian or other Pacific islander | 10 (1) | 0 (0) |
| Not reported or unknown | 105 (7) | 46 (44) |
| Ethnicity | ||
| Hispanic or Latino | 156 (10) | 44 (28) |
| Not Hispanic or Latino | 1303 (81) | 685 (53) |
| Not reported or unknown | 141 (9) | 66 (47) |
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP:A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.