Traitement de l’Hépatite C
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Traitement de l’Hépatite C Sans Interféron Patrick Marcellin. Hepatitis C. Where we are: The achievements. Hepatitis C: progress is accelerating. The conclusion of the PHC 2009. Cure = 100% in 10 years. Progress is accelerating. Earlier ? 2015 ?.

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Traitement de l h patite c sans interf ron patrick marcellin

Traitement de l’Hépatite C

Sans Interféron

Patrick Marcellin


Traitement de l h patite c sans interf ron patrick marcellin

Hepatitis C


Traitement de l h patite c sans interf ron patrick marcellin

Where we are:

The achievements


Hepatitis c progress is accelerating

Hepatitis C: progress is accelerating

The conclusion of the PHC 2009

  • Cure = 100% in 10 years


Progress is accelerating

Progress is accelerating

Earlier ?

2015 ?


Where we are better understanding of therapeutic targets

Where we areBetter understanding of therapeutic targets

Protease

Inhibitors

NS5A

Inhibitors

Polymerase

Inhibitors


Where we are better efficacy with triple therapy g1

80

70%

60

+30%

40%

40

20

0

2002

BI

2012

TRI

Where we areBetter efficacy with triple therapy (G1)

Jacobson et al. NEJM 2012

Poordad NEJM 2012


Svr cure

SVR = CURE

  • Undetectable HCV RNA in serum: 100%

  • Undectable HCV RNA in liver: ≈100%

  • Undectable HCV RNA in PBMCs: 100%

Marcellin et al. Annals of Intern Madicine 1997

Maylin et al. Gastroenterology 2009


Cure improved prognosis

1.0

0.8

SVR (-)

0.6

p < 0.001

0.4

0.2

SVR (+)

0

0

2

4

6

8

10

12

Time since last treatment (years)

Cure = improved prognosis

HCC in 300 cirrhotics

Cardoso et al. J Hepatol 2010


Cure improved prognosis1

1,0

SVR (+)

0,8

p < 0.001

SVR (-)

0,6

0,4

0,2

0,0

0

2

4

6

8

10

Time since last treatment (years)

Cure = improved prognosis

Survival in 300 cirrhotics

Cardoso et al. J Hepatol 2010


Reinforced screening and access to therapy decrease in hcv related mortality

Reinforced screening and access to therapy=decrease in HCV-related mortality

Deuffic-Durban et al. EASL 2011

Percentage of decreased mortality modelisation 2012 – 2021 France

%

100

- 19 %

80

- 83 %

60

40

20

0

PEG-IFN + RBV

Tritherapy PEG IFN + RBV + PI

Tritherapy + reinforced screening + improved access to therapy


Traitement de l h patite c sans interf ron patrick marcellin

Where we are:

the limitations


Where we are limitations

Where we are: limitations

Insufficient screening

Undiagnosed Pool2.5 million

Undiagnosed Pool1.8 million

Diagnosed Pool0.9 million

Diagnosed Pool1.6 million


Where we are limitations1

Where we are: limitations

Russia3M

Korea1M

US4M

Europa5M

Japan2M

China43M

Pakistan9M

Egypt12M

Vietnam7M

India10M

Brazil7M

170 million people HCV infected worldwide


Where we are limitations2

Where we are: limitations

Insufficient access to treatment


Where we are limitations3

Where we are: limitations

Access to treatment: the bottle necks

Diagnosed

Managed

Treated

Cured


Where we are limitations4

Where we are: limitations

Russia3M

Korea1M

US4M

Europa5M

Japan2M

China43M

Pakistan9M G3

Egypt12M G4

Vietnam7M G6

India10MG3

Brazil7M

High prevalence of G non1 in high prevalence countries


Traitement de l h patite c sans interf ron patrick marcellin

Where we are:

The hope is becoming reality


Ideal therapy

Ideal Therapy

  • 100% efficacy

  • IFN-free

  • All oral

  • Short duration

  • No resistance

  • Pan-genotypic

  • Well tolerated and safe

  • Low cost


Where we go

Where we go

Quadruple therapy: PEG-IFN+ RBV+ NS5AI + PIin G1 null responders: IFN free

%

100

90

80

60

36

40

20

0

BMS-790052 + BMS-650032 + PEG IFN + RBV

BMS-790052 + BMS-650032

Lok et al. NEJM 2012


Danoprevir mericitabine ribavirine in non responders g 1

danoprevir + mericitabine + ribavirine in non responders G 1

SVR 12

%

100

80

55

60

39

40

20

n/N

9/23

17/31

0

Partial Responders

Null Responders

Feld JJ, AASLD 2012


Ifn free ongoing trials summary

IFN-free ongoing trials: summary


Traitement de l h patite c sans interf ron patrick marcellin

Impact of treatment on mortality

Without treatment

With bitherapy PEG IFN + RBV

3000

2500

-14%

G1/4

2000

incidence annuelle de la mortalité liée au VHC

1500

-32%

G2/3

1000

500

0

1980

1985

1990

1995

2000

2005

2010

2015

2020

2025

Years

Deuffic-Durban et al. J Hepatol 2007


Reinforced screening and access to therapy decrease in hcv related mortality1

Reinforced screening and access to therapy=decrease in HCV-related mortality

Deuffic-Durban et al. EASL 2011

Percentage of decreased mortality modelisation 2012 – 2021 France

25

20

+ 83 %

15

+ 19 %

10

5

0

PEG-IFN + RBV

Tritherapy PEG IFN + RBV + PI

Tritherapy + reinforced screening + improved access to therapy


Traitement de l h patite c sans interf ron patrick marcellin

Where we go:

IFN free Therapy


Where we go1

Where we go

Quadruple therapy: PEG-IFN+ RBV+ NS5AI + PIin G1 null responders: IFN free

%

100

90

80

60

36

40

20

0

BMS-790052 + BMS-650032 + PEG IFN + RBV

BMS-790052 + BMS-650032

Lok et al. NEJM 2012


Danoprevir mericitabine ribavirine in non responders g 11

danoprevir + mericitabine + ribavirine in non responders G 1

SVR 12

%

100

80

55

60

39

40

20

n/N

9/23

17/31

0

Partial Responders

Null Responders

Feld JJ, AASLD 2012


Faldaprevir bi 207127 rbv naive g1

Faldaprevir + BI 207127 + RBV (naive G1)

400 mg TID BI 207127 + BI 201335 + RBV

600 mg TID BI 207127 + BI 201335 + RBV

100

100

100

82

80

73

67

60

Patients with HCV RNA <25 IU/mL (%)

40

40

20

6/15

14/17

10/15

17/17

11/15

17/17

0

Day 15

Day 22

Day 29

Zeuzem S, et al. Gatroenterology 2011


Abt 450 r abt 333 abt 267 rbv

ABT-450/r + ABT-333 + ABT-267 + RBV

SVR 12 (ITT)

98

93

100

87

89

80

85

60

SVR 12 (ITT)

40

20

0

8W

Naîve patient

12WNaïve Patients

12WNull Responders

Kowdley et al. AASLD 2012


Sofosbuvir gs 7977 gs 5885 rbv

Sofosbuvir (GS 7977) + GS 5885 + RBV

HCV RNA < 15 UI/ml

100

100

100

88

80

60

HCV RNA < 15 UI/ml

40

10

20

0

SOF + RBV

SOF + GS-5885 + RBV

Naive

Null responders

Naive

Null responders

Gane et al. AASLD 2012


Faldaprevir bi 207127 rbv naive g11

Faldaprevir + BI 207127 + RBV (naive G1)

400 mg TID BI 207127 + BI 201335 + RBV

600 mg TID BI 207127 + BI 201335 + RBV

100

100

100

82

80

73

67

60

Patients with HCV RNA <25 IU/mL (%)

40

40

20

6/15

14/17

10/15

17/17

11/15

17/17

0

Day 15

Day 22

Day 29

Zeuzem S, et al. Gatroenterology 2011


Abt 450 r abt 333 abt 267 rbv1

ABT-450/r + ABT-333 + ABT-267 + RBV

SVR 12 (ITT)

98

93

100

87

89

80

85

60

SVR 12 (ITT)

40

20

0

8W

Naîve patient

12WNaïve Patients

12WNull Responders

Kowdley et al. AASLD 2012


Sofosbuvir gs 7977 gs 5885 rbv1

Sofosbuvir (GS 7977) + GS 5885 + RBV

HCV RNA < 15 UI/ml

100

100

100

88

80

60

HCV RNA < 15 UI/ml

40

10

20

0

SOF + RBV

SOF + GS-5885 + RBV

Naive

Null responders

Naive

Null responders

Gane et al. AASLD 2012


The proof of concept

The Proof of Concept

100% efficacy

All oral

IFN-free

Short duration

No resistance

Pan-genotypic

Well tolerated and safe

Low cost

?

?


Hepatitis c progress is accelerating1

Hepatitis C: progress is accelerating

The conclusion of the PHC 2009

  • Cure = 100% in 2-3 years

  • One pill a day


Where we are limitations5

Where we are: limitations

Insufficient access to treatment


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