FDA BRIEF: Week of May 23, 2016
PROBUPHINE (Buprenorphine) Implant
Titan Pharmaceuticals Inc. San Francicso, CA and Braeburn Pharmaceuticals, Princeton, NJ, USA
INDICATION: Maintenance treatment of opioid dependence in patients who have achieved and sustained prolonged clinical stability on low-to-moderate doses of a transmucosal buprenorphine-containing product
- Opioid abuse and addiction have taken a devastating toll
- Need for new innovative treatment options to regain control
- Implant a better option that currently available pill or film
- Medication-assisted treatment (MAT) options important component of the FDA’s opioid action plan
- One of three top priorities for the DHHS’ Initiative to reduce prescription opioid and heroin related overdose, death and dependence.
REG PATHWAY: NDA
MECHANISM OF ACTION: Buprenorphine is a partial agonist at the muopioid receptor and an antagonist at the kappa-opioid receptor. Implant provides constant, low-level dose for six months
- Single randomized double-blind, double-dummy study (n=176), subjects meeting criteria for opioid dependence and clinically stable on sublingual buprenorphine, PROBUPHINE vs sublingual buprenorphine
- Endpoint: Detect opioid use, over the 6-month treatment period, measured by urine screening and self-reporting of illicit opioid use
- 63% PROBUPHINE vs 64% sublingual buprenorphine
- Boxed warning: Risk of implant migration, protrusion, expulsion and nerve damage
- Common side effects: Implant-site pain, itching, and redness, headache, depression, constipation, nausea, vomiting, back pain, toothache and oropharyngeal pain
AXUMIN (fluciclovine F 18) injection for PET imaging
Blue Earth Diagnostics, Ltd., Oxford, UK
INDICATION: For PET in men with suspected prostate cancer recurrence based on elevated blood prostate specific antigen (PSA) levels following prior treatment.
- Prostate cancer second leading cause of death from cancer
- In suspected cancer recurrence cases, accurate staging important in improving management and outcomes.
- Need for imaging tests to determine location of recurrent cancer when PSA is at very low levels
REG PATHWAY: NDA
MECHANISM OF ACTION: Fluciclovine F 18, synthetic amino acid transported across mammalian cell membranes by transporters LAT-1 and ASCT2, which are upregulated in prostate cancer cells. Fluciclovine F 18 taken up to a greater extent in prostate cancer cells vs. surrounding normal tissues.
- 2 studies in men with suspected recurrence of prostate cancer based on rising PSA levels following radical prostatectomy and/or radiotherapy
- Study 1 (n=105): Comparison of AXUMIN scans vs prostate biopsy. Consistent with on-site reads
- Study 2 : 96 AXUMIN vs C11 choline scan. Agreement between readings
- Clinical correlation, which may include histopathological evaluation of the suspected recurrence site, is recommended.
- Radioactive drug; should be handled with appropriate safety measures
- Commonly reported adverse reactions: Injection site pain, redness, and a metallic taste in the mouth
Epigenomics AG, Berlin, GERMANY
INDICATION FOR USE: Qualitative in vitro diagnostic test for the detection of methylated Septin 9 DNA associated with the occurrence of colorectal cancer (CRC)
REG PATHWAY: PMA, Priority Review because first of a kind device that uses breakthrough technology. Device Code: PHP
- Molecular and Clinical Genetics Advuisory Panel voted to approve; indicated in a second-line setting, post-approval study to evaluate the programmatic performance
- In vitro polymerase chain reaction (PCR) assay for the qualitative detection of methylated Septin 9 DNA isolated from patient plasma
- 3 components: Epi proColon Plasma Quick Kit, Epi proColon Sensitive PCR Kit, Epi proColon Control Kit
- Plasma Quick Kit: Extraction, purification and conversion of DNA from plasma.
- Sensitive PCR Kit: Amplify and detect the methylated Septin 9 (mSEPT9) target region and a control region in the β-actin gene (ACTB) in one PCR reaction
- Colon Control Kit: Test validity of each run
- Study 1: 68.2% sensitivity, 80.0% specificity vs colonoscopy results
- Study 2: 73.3% sensitivity, 81.5% specificity vs. colonoscopy results
- Study 3: Based on recommendations from advisory committee – to evaluate adherence in a study population with a history of non-compliance. 99.5% of the study population underwent screening with Epi proColon
- Patient perspective assessment: Epi proColon provides an option for adults unable or unwilling to undergo routine CRC screening tests
- Erroneous device results could delay detection of CRC
- False positive results could lead to an increased number of colonoscopies