AXUMIN Solution for injection Ref.[10080] Active ingredients: Fluciclovine ¹⁸F

Following intravenous administration, the tumor-to-normal tissue contrast is highest between 4 and 10 minutes after injection, with a 61% reduction in mean tumor uptake at 90 minutes after injection.

Distribution

Following intravenous administration, fluciclovine F 18 distributes to the liver (14% of administered activity), pancreas (3%), lung (7%), red bone marrow (12%) and myocardium (4%). With increasing time, fluciclovine F 18 distributes to skeletal muscle.

Excretion

Across the first four hours post-injection, 3% of administered radioactivity was excreted in the urine. Across the first 24 hours post-injection, 5% of administered radioactivity was excreted in the urine.

Carcinogenesis

No long term studies in animals have been performed to evaluate the carcinogenic potential of fluciclovine.

Mutagenesis

Fluciclovine was not mutagenic in vitro in reverse mutation assay in bacterial cells and in chromosome aberration test in cultured mammalian cells, and was negative in an in vivo clastogenicity assay in rats after intravenous injection of doses up to 43 mcg/kg. However, fluciclovine F 18 has the potential to be mutagenic because of the F 18 radioisotope.

Impairment of Fertility

No studies in animals have been performed to evaluate potential impairment of fertility in males or females.

The safety and efficacy of Axumin were evaluated in two studies (Study 1 and Study 2) in men with suspected recurrence of prostate cancer based on rising PSA levels following radical prostatectomy and/or radiotherapy.

Study 1 evaluated 105 Axumin scans in comparison to histopathology obtained by biopsy of the prostate bed and biopsies of lesions suspicious by imaging. PET/CT imaging generally included the abdomen and pelvic regions. The Axumin images were originally read by on-site readers. The images were subsequently read by three blinded independent readers. Table 4 shows the performance of Axumin in the detection of recurrence in each patient scan and, specifically, within the prostatic bed and extra-prostatic regions, respectively. The results of the independent read were generally consistent with one another and confirmed the results of the on-site reads.

Table 4. Performance of Axumin in Patients with Biochemically Suspected Recurrent Prostate Cancer, at the Patient Level and at the Prostate Bed and Extraprostatic Region Levels:

N = number of patient scans evaluated

The detection rate of Axumin seems to be affected by PSA levels [see Warnings and Precautions (5.1)]. In general, patients with negative scans had lower PSA values than those with positive scans. The detection rate (number with positive scans/total scanned) for patients with a PSA value of less than or equal to 1.78 ng/mL (1st PSA quartile) was 15/25, of which 11 were histologically confirmed as positive. In the remaining three PSA quartiles, the detection rate was 71/74, of which 58 were histologically confirmed. Among the 25 patients in the first PSA quartile, there were 4 false positive scans and 1 false negative scan. For the 74 patients with PSA levels greater than1.78 ng/mL, there were 13 false positive scans and no false negative scans.

Study 2 evaluated the concordance between 96 Axumin and C11 choline scans in patients with median PSA value of 1.44 ng/mL (interquartile range = 0.78 to 2.8 ng/mL). The C 11 choline scans were read by on-site readers. The Axumin scans were read by the same three blinded independent readers used for Study 1. The agreement values between the Axumin and C11 choline reads were 61%, 67% and 77%, respectively.