Gozetotide

GOZELLIX, after radiolabeling with Ga 68, 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. GOZELLIX, after radiolabeling with Ga 68, is a radioactive diagnostic agent 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 )

Kit for the preparation of Gallium Ga 68 Gozetotide Injection contains: Vial 1 (Gozetotide): 25 mcg of gozetotide as a white to off-white lyophilized powder in a multiple-dose vial Vial 2A (2.5 mL) or Vial 2B (6.4 mL) (Acetate Buffer): 150 mg anhydrous sodium acetate as a sterile clear colorless solution Vial 2A in Configuration A for use with cyclotron-produced Ga 68 via GE FASTlab or ARTMS QIS, or EZAG Gallia Pharm generator Vial 2B in Configuration B for use with IRE EliT Galli Eo generator Ampule (Ascorbic Acid Stabilizer): 500 mg/2 mL (250 mg/mL) of ascorbic acid (USP injection grade) as a sterile clear colorless solution After radiolabeling with Ga 68, Vial 1 contains up to 18,500 MBq (500 mCi) of Gallium Ga 68 Gozetotide Injection in 10 mL at calibration date and time as a clear, colorless to slightly yellow solution in a multiple-dose vial. Kit for the preparation of Gallium Ga 68 Gozetotide Injection contains: Vial 1 (Gozetotide): 25 mcg gozetotide as a lyophilized powder in a multiple-dose vial Vial 2A (2.5 mL) or Vial 2B (6.4 mL) (Acetate Buffer): 150 mg of anhydrous sodium acetate as a sterile solution Vial 2A in Configuration A for use with cyclotron-produced Ga 68 via GE FASTlab or ARTMS QIS, or EZAG generator Vial 2B in Configuration B for use with IRE generator Ampule (Ascorbic Acid Stabilizer): 500 mg/2 mL (250 mg/mL) ascorbic acid (USP injection grade) as a sterile solution. ( 3 ) After radiolabeling with Ga 68, Vial 1 contains up to 18,500 MBq (500 mCi) of Gallium Ga 68 Gozetotide Injection in 10 mL in a multiple-dose vial at calibration date and time.

None None ( 4 )

Risk for Misinterpretation: Gallium Ga 68 gozetotide uptake can be seen in a variety of tumor types and in non-malignant processes. Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended. ( 5.1 ) Radiation Risks: Ensure safe handling to protect patients and health care providers from unintentional radiation exposure. ( 2.1 , 5.2 ) Hypersensitivity Reactions to Sulfites: Ascorbic Acid Stabilizer contains sodium metabisulfite, a sulfite that may cause life-threatening hypersensitivity reactions including anaphylaxis. ( 5.3 )

5.1 Risk for Misinterpretation Image interpretation errors can occur with GOZELLIX PET. A negative image does not rule out the presence of prostate cancer and a positive image does not confirm the presence of prostate cancer. Gallium Ga 68 gozetotide uptake is not specific for prostate cancer and may occur with other types of cancer as well as non-malignant processes such as Paget's disease, fibrous dysplasia, and osteophytosis. The performance of GOZELLIX for imaging of biochemically recurrent prostate cancer seems to be affected by serum PSA levels and by site of disease. The performance of GOZELLIX for imaging of metastatic pelvic lymph nodes prior to initial definitive therapy seems to be affected by Gleason score [ see Clinical Studies (14.1 , 14.2) ] . Clinical correlation, which may include histopathological evaluation of the suspected prostate cancer site, is recommended.

5.2 Radiation Risks Gallium Ga 68 gozetotide contributes to a patient's overall long-term cumulative radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. Ensure safe handling to minimize radiation exposure to the patient and health care providers. Advise patients to hydrate before and after administration and to void frequently after administration [see Dosage and Administration (2.1 , 2.3) ] .

5.3 Hypersensitivity Reactions to Sulfites Ascorbic Acid Stabilizer contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

The most commonly reported adverse reactions include nausea, diarrhea, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Telix Pharmaceuticals (US) Inc. at 1-844-455-8638 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 GOZELLIX has been established based on two prospective studies of another formulation of gallium Ga 68 gozetotide in patients with prostate cancer [see Clinical Studies (14.1 , 14.2) ] . Below is a display of the adverse reactions in these studies. The safety of gallium Ga 68 gozetotide was evaluated in 960 patients in the PSMA-PreRP and PSMA-BCR studies, each receiving one dose of gallium Ga 68 gozetotide. The average injected activity was 188.7 ± 40.7 MBq (5.1 ± 1.1 mCi) [see Clinical Studies (14.1 , 14.2) ] . The most commonly reported adverse reactions were nausea, diarrhea, and dizziness, occurring at a rate of <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, can result in changes in uptake of gallium Ga 68 gozetotide in prostate cancer. The effect of these therapies on performance of gallium Ga 68 gozetotide PET has not been established.

8.1 Pregnancy Risk Summary GOZELLIX is not indicated for use in females. There are no available data with gallium Ga 68 gozetotide injection use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. All radiopharmaceuticals, including GOZELLIX, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. Animal reproduction studies have not been conducted with gallium Ga 68 gozetotide.

8.2 Lactation Risk Summary GOZELLIX is not indicated for use in females. There are no data on the presence of gallium Ga 68 gozetotide in human milk, the effect on the breastfed infant, or the effect on milk production.

8.4 Pediatric Use The safety and effectiveness of gallium Ga 68 gozetotide in pediatric patients have not been established.

8.5 Geriatric Use The efficacy of gallium Ga 68 gozetotide PET in geriatric patients with prostate cancer is based on data from two prospective studies [see Clinical Studies (14.1 , 14.2) ]. Of the total number of subjects in the PSMA-PreRP and PSMA-BCR studies, 691 of 960 (72%) patients were 65 years of age and older while 195 (20%) were 75 years of age and older. The efficacy and safety profiles of gallium Ga 68 gozetotide appear similar in younger adult and geriatric patients with prostate cancer and other reported clinical experience has not identified differences in responses between the elderly and younger adult patients.

Gallium Ga 68 gozetotide binds to PSMA. It binds to cells that express PSMA, including malignant prostate cancer cells, which usually overexpress PSMA. Gallium-68 is a β+ emitting radionuclide that allows positron emission tomography.