VIDAS Anti-HCV (30 308)

Launch Count Down 1

Hepatitis C
Epidemiology / Physiopathology

HCV Hepatitis C Virus

Discovery in 1989 RNA virus (10K bp) member of the Flaviviridae

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 Depending on HCV genotypes Type 4: Middle East, Egypt, Central Africa Type 5: South Africa different treatment efficacy 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

Hepatitis C Natural history

Around 85% of acute HCV infections evolve to Chronicity

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 (5UTR), Hybridation inverse

Presence of Antibodies: contact with the virus Presence of RNAs: active infection

HCV Genotyping

Helps in determining treatment indication, duration & dose of treatment

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:

HepC sero: + Transaminase: N

HepC sero: Transaminase:

HepC sero: Transaminase: N

Confirmation HCV Viral Load (+or neg)

Active/Chronic Hep C Fibrotest or biopsy Treatment

Old HCV Infection No treatment

Non viral Hepatitis Alternative diagnosis (Steatite or alcoholic hepatitis,)

Stop investigations
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Hepatitis C - Testing Algorithm

Patients with suspected HCV infection
ACUTE
Mostly asymptomatic

Ab Anti-HCV may NOT be detectable in early infection

CHRONIC
Anti-HCV + HCV RNA +

HCV RNA
(2-4 wks post infection)

If Immuno Compromised

Control @ 6-8 wks

+ Acute Hepatitis C

Confirmation test (RIBA, molecular, IA,)

Exclusion Past hepatitis + Chronic hepatitis

Testing algorithm dependant upon availibility of Molecular, confirmation scheme, pricing & reimbursement, testing sites,

Hepatitis C Serological tools

Classification
Performance improvement

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
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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.

VIDAS Anti- HCV

(30 308)

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VIDAS HCV Intended use

Clinical 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.

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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 Principle Kit size Sample volume Calibration Run time (reagent preparation) Result interpretation (Core, NS3, NS4) IgG Sandwich, ELFA 60 tests 100 l Every 28 days Around 40 mn (reagents to be used straight from the fridge, liquid C1/S1) < 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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Performances of VIDAS ANTI-HCV

population
Blood donors

n
4,766 450 5,104

study types
comparison to Prism comparison to Architect, Elecsys, Centaur, Ortho (plate) comparison to Prism

Specificity
studies

Pregnant women 114 comparison with Architect 119 (ie HSV, VZV, Syphillis, Interference related to other comparison with Architect HBV, HAV, HIV, ) ID (cross reaction) Interference related to test 40 (with Reumatoid factors or comparison with Architect Ab) format (cross reaction) Hospitalized
210 neg patients 200 neg patients comparison with Architect comparison with Vitros

population

study types

Sensitivity
studies

Clinical population

400 positive samples (different HepC comparison with Architect disease stage & 6 genotypes) 150 positive samples (incl. 22 comparison to Architect, Ortho (plate) dilutions) 439 positive patients (different HepC comparison with Vitros disease stage & 6 genotypes)

Clinical population Selected samples

97 well-characterized samples (anticomparison with Vitros & 2 immunoblots Core and anti-NS3 response) 30 commercial panels (14 from BBI, Seroconversion panels comparison with Architect, Ortho (plate) 16 from ZeptoMetrix)

Mutiple studies performed on various populations for performance assessment VIDAS Anti-HCV is comparable to other CE-marked assays

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VIDAS Anti-HCV - Launch Plan (tentative timelines)

READY - STEADY - GO !

Jun

Apr

May

Oct
Segmentation & Definition of Action plan
(for IB & New customers)

Jan

Jul

Market Investigation

CE Launch

Launch Preparation Action Plan implementation

Forecasts 2012 Precise Follow-up Follow-up of non-CE registrations

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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

Performances

Grey zone: Results between 0,8 and 1,0 must be interpreted with caution

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VIDAS ANTI-HCV
70% % Distribution of negative samples (study on 4766 blood donors)

60%

50% PTB3 PTB5 PTB3+4+5+6 40% PTB4 PTB6

30%
0,5 cut off PTB3: PTB4: PTB5: PTB6: cut off 2,31% 0,80% 1,30% 0,70%

20%

10%

PTB3: PTB4: PTB5: PTB6:

0,50% 0,00% 0,43% 0,00%

0% <0,13 0,13-0,25 0,25-0,50 0,51-0,75 0,75-0,99 >1 index

Scientific Communication
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 Immunoassay
Sold by SIEMENS for ORTHO ADVIA CENTAUR
100% (449/449) [99,18 to 100%] (no immunocompromized patients ex HIV) 99,9% (5217/5222) [ to 99,97%]

ORTHO VITROS
100%

ROCHE COBAS Elecsys

100% (n=1057) [99,72 to 100%]

BECKMAN COULTER ACCESS (HCV Ab PLUS)

100% (299 positive samples (Chronic HCV) and 67 seroconversion samples )

ABBOTT ARCHITECT ANTI-HCV

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%] 99,6% (8942 serum & plasma specimens from Blood donors and plasmapheresis donors) [99,45 to 99,71%]

Sensitivity

99,76%

Specificity

99,71% (european blood donors) 99,17% (hopsitalized patients, dialysis patients, pregnant w omen) Yes ( 0,9 to < 1)

Gray zone Technology Stability on aboard Delay between calibration Number of tests/kit Detection of coating Sample type sample volume Reaction Time Type of controls Kit after 1st use sample Approved

Yes ( 0,8 to < 1)

Yes ( 0,9 to < 1)

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 Yes ( 0,9 to < 1)

if needed possibility to use one (0,80 to 0,99) Chemiluminescence microparticules immunoassay 30 days

ELISA sandw ich indirect 41 days 28 days

ELISA indirect < 8 w eeks 28 days

ELISA sandw ich 72h (on aboard betw een 20 & 25C)

ELISA Indirect (Detection of HCV Ab) 28 days 28 days

200

100

100

100 / 500

HCV synthetic peptide & HCV recombinant Ag (c22, c200 recombinant Ag + NS5) Recombinant Ag: c200 derives from NS3 & NS4) and NS5 + Synthetic peptide: c22 (core prot) Serum/Plasma (EDTA/Plasma heparin) 10L One positive control & one negative Serum, Plasma (EDTA, Heparin, Citrate) 20L 55min 2 Controls <8 w eeks

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

Serum, Plasma 40L 18 min 2 Controls 8 w eeks

Serum, Plasma (EDTA, Heparin, Citrate) 25L 55 min (at 37C) 2 controls (1 positive & one negative) 28 days (2-10C)

Serum, Plasma 150L ? 2 controls (1 positive & 1 negative)

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CE FDA FDA CE FDA

Communication Plan Brochure (1/2)

Brochure
Finalization of final version

recto

verso

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Communication Plan Brochure (2/2)

inside

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Communication Plan Sticker / Banner

LiveLink @ http://doclink/Livelink/livelink.exe?func=ll&objId=29445293&objAction=browse&sort=name

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

Hepatitis Interpretation Ruler

ongoing
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FAQ
Your First Questions

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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 5093% of patients with acute hepatitis C and 5070% of patients with chronic hepatitis C [810]. 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

Hepatitis = Complex Clinical picture

need for serological tools to aid in the Hepatitis diagnosis

VIDAS Hepatitis solution

screening for HAV, HBV HCV precise diagnosis - Anti HAV / HAV IgM
- HBsAg / Anti-HBcT / HBc IgM / Anti-HCV Anti HBsT / Anti-HBE/HBE Ag

VIDAS Hepatitis panel

Competitive panel adapted to Small volume screening Diagnosis confirmation
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VIDAS HBV range - Reminder

The VIDAS system + the complete range + the Quality From Small/medium labs to big laboratories

HBcIgM Ultrasensitive Quantitative Pack of 30 tests HBcT Excellent specificity Compatible protocol with HAVT, HBE, HBET, HBL Anti-HBsT Accuracy of the results Good sensitivity

Capacity adapted to lab activity Load & Go Unit tests Long MTBF Kit sizes adapted
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
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Objectives of VIDAS HCV launch 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 :

VIDAS ID
35 references 15 pathologies/vectors

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
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