Structural basis for recognition of arginine methylated Piwi
Epi proColon: a plasma test for methylated SEPT9 DNA for ... · Epi proColon: a plasma test for...
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Epi proColon: a plasma test for methylated SEPT9 DNA for
colorectal cancer screening.
Dr. Jeffrey Cossman
EPI proColon
Dr. Jeffrey Cossman
• FDA approved as a screening test for colorectal cancer
• Specifically approved by FDA for the 35% of eligible Americans who go unscreened
• Approved, and in use, in Europe, China and other countries
• The clinical value has been firmly established in large scale control and prospective clinical trials
Development Studies – Case Control
Dr. Jeffrey Cossman
Study # Samples Sensitivity Specificity Assay
Study 1 312 52 95 Experimental Workflow
Study 2 600 57 96
Study 3 725 48 93
Study 4 370 48 96
Study 5 550 72 90
Study 6 269 74 92 mSEPT9 Detection Assay
Study 7 245 69 89
Study 8 158 71 99 Abbott mS9 Assay
Study 9 257 67 88 Epi proColon Assay (Duplicate)
Study 10 128 86 93 Epi proColon Assay (Triplicate)
Study 11 168 90 89 ARUP mSEPT9 Assay
Study 12 256 91 87 Epi proColon 2nd Generation Prototype
Total 4,038
Prospective Analysis - PRESEPT
Dr. Jeffrey Cossman
2010 PRESEPT Study PRESEPT Study post-hoc
Subjects collected
7,940 7,940
Subjects tested
Stratified Random Sampling
1516 1478
Sensitivity 48.2% 63.9%
Specificity 91.5% 88.4%
Assay / Kit
Epi proColon® CE
(duplicate)
Epi proColon® CE
(triplicate)
Church et.al., Gut. 63:317-325. Doi10.1136/gutjnl-2012-304149
Prospective Analysis – Epi proColon
Dr. Jeffrey Cossman
2012 Prospective Performance Evaluation
Subjects tested 1544
Sensitivity 68.2% (CI 53.4-80.0%)
Specificity 80.0% (CI 77.9-82.1%)
Assay / Kit
Epi proColon FDA
Potter et.al., Clinical Chemistry. 60(9):1183-1191.
Comparison to FIT – SEPT9
Dr. Jeffrey Cossman
2014 SEPT9 FIT
Subjects tested 301 290
Sensitivity 73.3% (CI 63.9-80.9%) 74/101
68.0% (CI 58.2-76.5%) 66/97
Specificity 81.5% (CI 75.5 – 86.3) 37/200
97.4% (CI 94.1-98.9%) 5/193
Assay / Kit Epi proColon FDA OC-Auto (100ng)
Johnson et.al. PLOS ONE. 9(6):1-8. e98238
Comparison to FIT – Stage Detection
Dr. Jeffrey Cossman
2014 Epi proColon FIT
Stage 0 100% (2/2) 0.0% (0/2)
Stage I 61.5% (16/26) 65.4% (17/26)
Stage II 80.0% (16/20) 80.0% (16/20)
Stage III 65.2% (15/23) 82.6% (19/23)
Stage IV 92.3% (12/13) 58.3% (7/12)
Unclassified 76.5% (13/17) 50.0% (7/14)
Total 73.3% (74/101) 68.0% (66/97)
Johnson et.al. PLOS ONE. 9(6):1-8. e98238
SEPT9 Studies- Chinese Population
Name of presenter
Jin et.al. J Gastroenterol Hepatol. 2014 Dec 4. doi: 10.1111/jgh.12855.
Opportunistic Screening - China
Dr. Jeffrey Cossman
Wu et.al. J Mol Diagn 2016; http://dx.doi.org/10.1016/ j.jmoldx.2016.02.005
Future Studies
• Longitudinal Performance – as part of US FDA Post Approval
• Comparison to FIT in matched patients- Germany
• Opportunistic Screening & General Population screening – China
• Extension of indication – familial syndromes US
• Extension of indication – response monitoring – South America
Dr. Jeffrey Cossman
Summary
• Methylated SEPT9 testing is available in approved form in the US, Europe, China and other countries
• Performance levels are comparable in different geographies – depend on the algorithm
• Early stage detection >60% in multiple studies
• When combined with FIT, sensitivity ~90%
• In positives who went on to scope >50% had lesions
• In a behavioral study, 99.5% went on to take the test
• A blood test option will complement other methods and improve screening rates
Dr. Jeffrey Cossman