Piflufolastat F-18

PYLARIFY TRUVU is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer: with suspected metastasis who are candidates for initial definitive therapy with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level PYLARIFY TRUVU is a radioactive diagnostic drug indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer: with suspected metastasis who are candidates for initial definitive therapy with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level ( 1 )

Injection: 37 MBq/mL to 4,440 MBq/mL (1 mCi/mL to 120 mCi/mL) of piflufolastat F 18 in up to 55 mL at end of synthesis as a clear, colorless to pale yellow solution in a multiple-dose vial Injection: 37 MBq/mL to 4,440 MBq/mL (1 mCi/mL to 120 mCi/mL) of piflufolastat F 18 at end of synthesis in a multiple-dose vial ( 3 )

None. None. ( 4 )

Risk of Image Misinterpretation : PYLARIFY TRUVU uptake can be seen in a variety of tumor types as well as in non-malignant processes and normal tissues. Image interpretation errors can occur with PYLARIFY TRUVU imaging. ( 5.1 ) Hypersensitivity Reactions : Monitor patients for hypersensitivity reactions, particularly patients with a history of allergy to other drugs and foods. ( 5.2 ) Radiation Risk : Ensure safe drug handling to protect patients and health care workers from unintentional radiation exposure. ( 5.3 )

5.1 Risk of Image Misinterpretation Imaging interpretation errors can occur with PYLARIFY TRUVU imaging. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. The performance of PYLARIFY TRUVU for imaging of patients with biochemical evidence of recurrence of prostate cancer seems to be affected by serum PSA levels [ see Clinical Studies (14) ]. The performance of PYLARIFY TRUVU for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by risk factors such as Gleason score and tumor stage [ see Clinical Studies (14) ]. Piflufolastat F 18 uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes and in normal tissues. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.

5.2 Hypersensitivity Reactions Monitor patients for hypersensitivity reactions, particularly patients with a history of allergy to other drugs and foods. Reactions may not be immediate. Always have trained staff and resuscitation equipment available.

5.3 Radiation Risks PYLARIFY TRUVU exposes patients to radiation [see Dosage and Administration (2.6) ] . Radiation exposure is associated with a dose-dependent increased risk of cancer. Ensure safe handling and preparation procedures to protect patients and health care workers from unintentional radiation exposure. Advise patients to hydrate before and after administration and to void frequently after administration [see Dosage and Administration (2.3) ] .

The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence > 0.5%) are headache, dysgeusia, and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Aphelion LLC at 1-800-362-2668 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of PYLARIFY TRUVU has been established based on data from clinical studies of another formulation of piflufolastat F 18 in patients with prostate cancer [see Clinical Studies (14) ] . The results of these two studies are presented below. The safety population included 593 patients, each receiving one dose of piflufolastat F 18. The average injected activity was 340 ± 26 MBq (9.2 ± 0.7 mCi). The adverse reactions reported in >0.5% of patients within the studies are shown in Table 2. In addition, a hypersensitivity reaction was reported in one patient (0.2%) with a history of allergic reaction. Table 2. Adverse Reactions with a Frequency >0.5% in Patients Who Received Piflufolastat F 18 (n = 593) Adverse Reaction n (%) Headache 13 (2%) Dysgeusia 10 (2%) Fatigue 7 (1%)

Androgen deprivation therapy and other therapies targeting the androgen pathway Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, may result in changes in uptake of piflufolastat F 18 in prostate cancer. The effect of these therapies on performance of PYLARIFY TRUVU PET has not been established.

8.1 Pregnancy Risk Summary PYLARIFY TRUVU is not indicated for use in females. There is no information on the risk of adverse developmental outcomes in pregnant women or animals with the use of piflufolastat F 18. All radiopharmaceuticals, including PYLARIFY TRUVU, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose.

8.2 Lactation Risk Summary PYLARIFY TRUVU is not indicated for use in females. There is no information on the presence of piflufolastat F 18 in human milk, the effect on the breastfed infant, or the effect on milk production.

8.4 Pediatric Use The safety and effectiveness of PYLARIFY TRUVU in pediatric patients have not been established.

8.5 Geriatric Use Of the 593 patients in completed clinical studies of piflufolastat F 18, 355 (60%) were ≥65 years old, while 76 (12.8%) were ≥75 years old. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Piflufolastat F 18 binds to cells that express prostate-specific membrane antigen (PSMA), including malignant prostate cancer cells, which usually overexpress PSMA. Fluorine-18 (F 18) is a β+ emitting radionuclide that enables positron emission tomography.