Post on 22-Aug-2014
transcript
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VIDAS Anti-HCV (30 308)
Launch Count Down 1
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Hepatitis C
Epidemiology / Physiopathology
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Discovery in 1989
RNA virus (10K bp)
member of the Flaviviridae
HCV – Hepatitis C Virus
Variable genome (6 genotypes & mutations) and geographical distribution • Type 1: Northern EU, North US, Southern & Eastern EU, Japan
• Type 2 : less frequent
• Type 3: South-East Asia
• Type 4: Middle East, Egypt, Central Africa
• Type 5: South Africa
• Type 6-11: Asia
Blood-borne virus transmitted via:
•contaminated needles: injecting drug use (60%)
•Hemodialysis
•Transplant or transfusion (before screening: 10%)
•Tatooing, body-piercing, using unsterilized needles
•Sexual intercourse (15%)
•Perinatal: infant born to HCV infected mother
Depending on HCV genotypes :
different treatment efficacy
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Hepatitis C – Natural history
Around 85% of acute HCV
infections evolve to Chronicity
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Hepatitis C – Disease Markers
Diagnosis
Biochemical measurements of liver function (bilirubin, albumin, ALT, …)
Specific Diagnostic tools • Antibodies anti-HCV
• Core Ag (or combo Ag/Ab 4th gen)
• Viral RNA: TMA, quantitative RT-PCR
• Genotyping, sequencing (5’UTR), Hybridation inverse
HCV Genotyping Helps in determining treatment indication, duration & dose of treatment
Presence of Antibodies: contact with the virus
Presence of RNAs: active infection
Non viral Hepatitis
Alternative diagnosis
(Steatite or alcoholic hepatitis,…)
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Hepatitis C – Patient Flow
Patients
with clinical signs (fatigue, fever, nausea…)
without symptoms but with risk factors (transfusion, injecting drug,…)
Hepatic status Transaminase / Hep A / Hep B / Hep C serology
HepC sero: +
Transaminase: N
HepC sero: -
Transaminase:
HepC sero: +
Transaminase:
HepC sero: -
Transaminase: N
Active/Chronic Hep C
Fibrotest or biopsy
Treatment
Confirmation
HCV Viral Load (+or neg)
Stop
investigations
Old HCV Infection
No treatment
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ACUTE Mostly asymptomatic
CHRONIC Anti-HCV
HCV RNA
Exclusion
Past hepatitis
- +
+ -
If Immuno
Compromised
HCV RNA
(2-4 wks post infection)
+ - Acute Hepatitis C Control @
6-8 wks
Hepatitis C - Testing Algorithm
Confirmation test
(RIBA, molecular, IA,…)
- +
Chronic hepatitis
Ab Anti-HCV may
NOT be detectable
in early infection
Testing algorithm dependant upon availibility of Molecular,
confirmation scheme, pricing & reimbursement, testing sites,…
Patients with suspected HCV infection
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Hepatitis C – Serological tools
Classification
•1st generation assay
Detection of Abs against recombinant NS4 protein
•2nd generation assay
Detection of Abs against recombinant Core, NS3, NS4 proteins
•3rd generation assay
Detection of Abs against recombinant Core, NS3, NS4, +/- NS5 proteins (improved NS3 detection)
•4th generation assay
Combined detection of Abs against recombinant Core, NS3, NS4 proteins and HCV Ag
Best sensitivity for Antibody detection reported for 3rd
generation Anti-HCV assay
NO clear IA reference methods trends to use confirmation by
Molecular and Blot methods
Pe
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VIDAS Anti-HCV
3rd vs 4th generation HCV assays ?
Due to the low HepC prevalence, most clinicians are satisfied with « new »
3rd generation HCV assays for diagnosis
Most often, use of Molecular tests for 1) confirmation (cf national guidelines)
and 2) genotyping for treatment optimization.
HCV acute infection is mainly asymptomatic and patients visits doctors
when presence of symptoms detection possible by « New » 3rd generation
assays
4th generation combo assay, although detecting an acute infection 20 days
earlier than a 3rd gen assay, are less sensitive for Ab detection (Chevaliez
et al, 2010, Clinical Microbiology & Infection):
“Nevertheless, core antigen detection is less sensitive than HCV RNA level
detection and the core antigen to HCV RNA ratio may vary slightly from one
infected patient to another.”
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VIDAS Anti- HCV (30 308)
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VIDAS HCV – Intended use
VIDAS Anti-HCV assay may be used for :
Qualitative detection of antibodies to Hepatitis C virus in human
serum or plasma
Aid in the diagnosis : in conjunction with other clinical information
in individuals with symptoms of hepatitis and in individuals at risk for
hepatitis C infection. It is also used in combination with HBV and HAV
assays to form a panel for the differential diagnosis of viral hepatitis.
Clinical Intended Use
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VIDAS anti-HCV - Principle
Assay construction and use of peptides specifically
designed for the assay
Raw material design different from other tests in the market
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VIDAS Anti-HCV – Main Characteristics
VIDAS Anti-HCV
Detection (Core, NS3, NS4) IgG
Principle Sandwich, ELFA
Kit size 60 tests
Sample volume 100 µl
Calibration Every 28 days
Run time
(reagent preparation)
Around 40 mn
(reagents to be used straight from
the fridge, liquid C1/S1)
Result interpretation < 1 : negative
≥ 1.00 : positive
Convenient product characteristics to facilitate cost control and ease of use
VIDAS Anti-HCV provides increased attractiveness to our VIDAS
Hepatitis offer (in addition to HAV/HBV)
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Specificity
studies
Sensitivity
studies
Mutiple studies performed on various populations for performance
assessment VIDAS Anti-HCV is comparable to other CE-marked
assays
Performances of VIDAS ANTI-HCV
population n study types4,766 comparison to Prism
450 comparison to Architect, Elecsys, Centaur, Ortho (µplate)
5,104 comparison to Prism
Pregnant women 114 comparison with Architect
Interference related to other
ID (cross reaction)
119 (ie HSV, VZV, Syphill is,
HBV, HAV, HIV, …) comparison with Architect
Interference related to test
format (cross reaction)
40 (with Reumatoid factors or
Ab)comparison with Architect
210 neg patients comparison with Architect
200 neg patients comparison with Vitros
Blood donors
Hospitalized
population n study types400 positive samples (different HepC
disease stage & 6 genotypes)comparison with Architect
150 positive samples (incl. 22
dilutions)comparison to Architect, Ortho (µplate)
Clinical population439 positive patients (different HepC
disease stage & 6 genotypes)comparison with Vitros
Selected samples97 well-characterized samples (anti-
Core and anti-NS3 response)comparison with Vitros & 2 immunoblots
Seroconversion panels30 commercial panels (14 from BBI,
16 from ZeptoMetrix)comparison with Architect, Ortho (µplate)
Clinical population
VIDAS Anti-HCV - Launch Plan (tentative timelines)
READY - STEADY - GO !
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Market
Investigation
Ju
n
Oct
Ap
r
Jan
Segmentation &
Definition of Action plan (for IB & New customers)
Ma
y
Ju
l
Launch Preparation
CE Launch
Forecasts 2012 – Precise Follow-up
Follow-up of
non-CE registrations
Action Plan implementation
Project update
CE Registration Finalization of review by GMED for CE-marking
Lots’ release by GMED with Expiry 1) Sept 2012 and 2) Nov 2012
Launch expected on week 15 (between April 10-14)
Package Insert Validation by GMED BUT addition of insert in 1st lots
Finalization of translations
PI to be sent asap
Recommended Pricing Higher HBsAg
Similar to HIV
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Performances
Grey zone: Results between 0,8 and 1,0 must be interpreted with caution
VIDAS ANTI-HCV
Distribution of negative samples
(study on 4766 blood donors)
0%
10%
20%
30%
40%
50%
60%
70%
<0,13 0,13-0,25 0,25-0,50 0,51-0,75 0,75-0,99 >1index
%
PTB3 PTB4
PTB5 PTB6
PTB3+4+5+6
cut off0,5 cut off
PTB3: 2,31%
PTB4: 0,80%
PTB5: 1,30%
PTB6: 0,70%
PTB3: 0,50%
PTB4: 0,00%
PTB5: 0,43%
PTB6: 0,00%
Scientific Communication
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Posters
- VIDAS Anti-HCV poster at ECCMID (London, 31st March-03rd April 2012)
- VIDAS Anti-HCV abstract submitted the congress 14th ISVHLD ( Shanghai,22-25 June 2012)
Articles
- ongoing
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Hepatitis C - Competition
HCV ImmunoassaySold by SIEMENS for
ORTHO
ORTHO ROCHE BECKMAN COULTER ABBOTT
ADVIA CENTAUR VITROS COBAS Elecsys ACCESS (HCV Ab PLUS) ARCHITECT ANTI-HCV
Sensitivity
100% (449/449)
[99,18 to 100%]
(no immunocompromized patients
ex HIV)
100% 100% (n=1057)
[99,72 to 100%]
100% (299 positive samples
(Chronic HCV) and 67
seroconversion samples )
99,1% (117 specimen: 50 patients
w ith Chronic HCV, 42 anti-HCV
and HCV RNA positive, 25 at
increased risk of HCV infection)
[96,77 to 99,89%]
Specificity
99,9% (5217/5222)
[ to 99,97%]
99,76% 99,71% (european blood
donors)
99,17% (hopsitalized patients,
dialysis patients, pregnant
w omen)
99,85% (2012 samples tested
from BB donors).
99,5% (692 samples from
hospitalised patients) vs SDP
DECISCAN HCV plus and 99,2%
vs RIBA
99,6% (8942 serum & plasma
specimens from Blood donors and
plasmapheresis donors)
[99,45 to 99,71%]
Gray zoneYes (≥ 0,8 to < 1) Yes (≥ 0,9 to < 1) Yes (≥ 0,9 to < 1) Yes (≥ 0,9 to < 1) if needed possibility to use one
(0,80 to 0,99)
TechnologyELISA sandw ich indirect ELISA indirect ELISA sandw ich ELISA Indirect (Detection of HCV
Ab)
Chemiluminescence
microparticules immunoassay
Stability on aboard41 days < 8 w eeks 72h (on aboard betw een 20 &
25°C)
28 days 30 days
Delay between
calibration
28 days 28 days 28 days
Number of
tests/kit
200 100 100 100 / 500
Detection of
coating
HCV synthetic peptide &
recombinant Ag
Recombinant Ag: c200 derives
from NS3 & NS4) and NS5 +
Synthetic peptide: c22 (core prot)
HCV recombinant Ag (c22, c200
+ NS5)
HCV recombinant Ag HCV synthetic peptid &
recombinant Ag (NS3 and NS4
region)
HCV recombinant Ag
HCr43: NS3 and core regions
c100-3: NS3 and NS4
Sample typeSerum/Plasma (EDTA/Plasma
heparin)
Serum, Plasma (EDTA, Heparin,
Citrate)
Serum, Plasma Serum, Plasma (EDTA, Heparin,
Citrate)
Serum, Plasma
sample volume 10µL 20µL 40µL 25µL 150µL
Reaction Time 55min 18 min 55 min (at 37°C) ?
Type of controlsOne positive control & one
negative
2 Controls 2 Controls 2 controls (1 positive & one
negative)
2 controls (1 positive & 1 negative)
Kit after 1st use
sample
<8 w eeks 8 w eeks 28 days (2-10°C)
Approved CE FDA FDA CE FDA
Brochure Finalization of final version
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recto verso
Communication Plan – Brochure (1/2)
Communication Plan – Brochure (2/2)
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inside
Communication Plan – Sticker / Banner
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Sticker For cross marketing actions : To be used preferably on VIDAS Hep/HIV kits
Centralization of stickers’ order: to return to Josephine MASI
before March 30th
multiple of 500
free of charge
E-mail Banners Banner for regular E-mailing to customers : great opportunity to announce the launch of VIDAS Anti-HCV
and push for requests.
2 e-mail banners
LiveLink @ http://doclink/Livelink/livelink.exe?func=ll&objId=29445293&objAction=browse&sort=name
Hepatitis Interpretation Ruler ongoing
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FAQ
Your First Questions…
FAQ
To ensure fast & thorough FU of
customers/teams needs and questions
Hepatitis C virus: overview
Technical points
Results and interpretation of HCV immunoassays
Send additional questions
Provide feedback @ the following survey:
http://www.surveymonkey.com/s/MP5RZQY
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VIDAS Anti-HCV
3rd vs 4th generation HCV assays? [continued]
Patient management is different between HIV and HCV
(excluding Blood Bank):
- For HIV: need to reduce seroconversion window to the minimum as virus is the
most infectious in the first weeks of infection strong need for combo Ag/Ab
detection
- For HCV: less urgency, need to identify genotype for treatment optimization due
to low prevalence.
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VIDAS Anti-HCV
Value of NS5 ?
Value of NS5 is contraversial and can lead to additional risk of false positives (Piro et al, Blood Transfus 2008 ; Bossi & Galli, JCV, 2004):
“In our series, eight out of nine subjects (89%) with isolated reactivity to NS-5 repeatedly tested negative with the HCV-RNA and did not seroconvert throughout the follow-up period. Our data do, therefore, support other authors„ conclusions (6,12)
that NS-5 reactivity in blood donors is mostly non-specific.”
Detection of anti-HCV IgM ?
Most HCV antibody assays are detecting anti-HCV IgG the role of Anti-HCV IgM during HCV infection is unclear and cannot be used as a reliable marker of acute infection (Chevaliez, Clin Microbiol Infect 2011):
“The significance of the presence of anti-HCV IgM during HCV infection is unclear. Anti-HCV IgMs have been reported in 50–93% of patients with acute hepatitis C and 50–70% of patients with chronic hepatitis C [8–10]. Therefore, anti-HCV IgM cannot be used as a reliable marker of acute HCV infection and, so far, IgM assays have not been used in clinical practice.”
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VIDAS Hepatitis panel : HAV, HBV, HCV
VIDAS Hepatitis solution
screening for HAV, HBV
precise diagnosis
- Anti HAV / HAV IgM
- HBsAg / Anti-HBcT / HBc IgM /
Anti HBsT / Anti-HBE/HBE Ag
HCV
Hepatitis = Complex Clinical picture
need for serological tools to aid in the Hepatitis diagnosis
VIDAS Hepatitis panel Competitive panel adapted to
Small volume screening
Diagnosis confirmation
Anti-HCV
VIDAS HBV range - Reminder
HBcT
• Excellent specificity
• Compatible protocol with
HAVT, HBE, HBET, HBL
From Small/medium labs to big laboratories
Capacity adapted to lab activity
Load & Go
Unit tests
Long MTBF
Kit sizes adapted
Anti-HBsT
Accuracy of the results
Good sensitivity
HBcIgM
Ultrasensitive
Quantitative
Pack of 30 tests
Hbe / anti-HBe
Suitable for small series
Hepatitis protocol same for
HAVT, HBCT, HBL
HBsAg Ultra
• Ultrasensitive
• Highly specific
• Wide detectability of mutants
• Detect all genotypes
• Compatible protocol with HAVT,
HBE, HBET, HBCT, HBL
• The VIDAS system + the complete range + the Quality
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1 Add “One More” parameter onto our Installed base
Target HBV/HAV installed base
2 Bring back the spotlights onto our
Infectious Disease menu to increase
revenue for the whole ID panel
Be opportunistic and push : small routine and/or complementary/confirmation testing
3 Attract new customers thanks to our ID/Esoteric and
full VIDAS solution
the VIDAS solution can be tailored to customer needs
Objectives of VIDAS HCV launch
VIDAS ID 35 references
15 pathologies/vectors
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