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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

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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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