Clinical Pharmacology Corner: FDA Approves AXUMIN (fluciclovine F 18) Injection

FDA Approves AXUMIN^TM (fluciclovine F 18) Injection for Positron Emission Tomography (PET) Imaging in Men with Suspected Prostate Cancer Recurrence

On May 27, 2016, the U.S. Food and Drug Administration (FDA) approved AXUMIN (fluciclovine F 18) injection for positron emission tomography (PET) imaging in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment. The approved recommended dosage is 370 MBq (10 mCi) AXUMIN injection administered as an intravenous bolus injection followed by an intravenous flush of sterile Sodium Chloride Injection, 0.9% to ensure full delivery of the dose.

Image interpretation errors can occur with Axumin PET imaging. A negative image does not rule out the presence of recurrent prostate cancer and a positive image does not confirm the presence of recurrent prostate cancer. Fluciclovine F 18 uptake is not specific for prostate cancer and may occur with other types of cancer and benign prostatic hypertrophy in primary prostate cancer. Clinical correlation, which may include histopathological evaluation of the suspected recurrence site, is recommended.

Mechanism of Action (MOA), General Pharmacokinetics (PK) and Pharmacodynamics (PD) of AXUMIN (fluciclovine F 18) injection

• MOA: Fluciclovine F 18 is a radioactive diagnostic agent transported across cell membranes by amino acid transporters (LAT1 and ASCT2), which are upregulated in prostate cancer cells. Fluciclovine F18 is taken up to a greater extent in prostate cancer cells compared with surrounding normal tissues.
• Dosimetry: The organs receiving the highest radiation absorbed doses are the pancreas (38 mGy), cardiac wall (19 mGy), and uterine wall (17 mGy), for an administered radioactivity of 370MBq (10 mCi).
• Distribution: Fluciclovine F 18 distributes to the liver (14% of administered activity), pancreas (3%), lung (7%), red bone marrow (12%), and myocardium (4%) following intravenous administration. With increasing time, fluciclovine F 18 distributes to skeletal muscle.
• Excretion: Three percent of administered activity was excreted in the urine four hours post- injection. Five percent of administered activity was excreted in the urine 24 hours post-injection.
• Pharmacodynamics: The tumor-to-normal tissue contrast is highest between 4 and 10 minutes after injection. Mean tumor uptake is decreased by 61%, 90 minutes after injection.

Safety and Efficacy

Efficacy

The safety and efficacy of Axumin were evaluated in two trials in men with suspected recurrence of prostate cancer based on rising PSA concentrations following radical prostatectomy and/or radiotherapy. One hundred and five Axumin scans from 99 patients in Trial 1 were evaluated in comparison to the histopathology obtained by biopsy of the prostate bed and biopsies of suspicious lesions identified by imaging. PET/CT imaging generally included the abdomen and pelvic regions. In the prostate bed region, true positive reads ranged from 49-59% for three readers. For the extra prostatic region, true positive reads ranged from 88-93% for three readers.

The detection rate of Axumin seems to be affected by PSA values. 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 than 1.78 ng/mL, there were 13 false positive scans and no false negative scans.

C 11 choline is a radioactive diagnostic agent for PET imaging of patients with suspected prostate cancer recurrence. In Trial 2, the concordance between 96 Axumin and C 11 choline scans from 88 patients was evaluated. Agreements between the Axumin reads (three independent readers) and C 11 choline reads (single onsite reader) were 61%, 67% and 77%.

Safety

Adverse reactions were reported in ≤1% of subjects during clinical trials with Axumin. The most common adverse reactions were injection site pain, injection site erythema and dysgeusia.

---

Full prescribing information is available at http://go.usa.gov/cSjSR.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

The Office of Clinical Pharmacology (OCP) regulatory reviews for new drugs or biologics are often available for viewing shortly following approval at the Agency's Drugs@FDA website (http://go.usa.gov/cSjhm).

The Office of Clinical Pharmacology (OCP) is pleased to announce the launch of the e-mail subscription service Clinical Pharmacology Corner. This is a free service from the U.S. Food & Drug Administration (FDA) to provide occasional updates from the OCP regarding newly approved therapies, new regulatory and scholarly publications, upcoming events and other items of interest. Subscribe today (https://public.govdelivery.com/accounts/USFDA/subscriber/new?topic_id=USFDA_407)

We always welcome your thoughts regarding the format, content, and utility of information you receive via this Burst email initiative. Comments may be sent via email to ocp@fda.hhs.gov.

This burst was prepared by Office of Clinical Pharmacology, Office of Translational Sciences, CDER, FDA.

---

FDA/Center for Drug Evaluation and Research (CDER)
Office of Translational Sciences
Office of Clinical Pharmacology
Email: ocp@fda.hhs.gov