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Traitement de l’Hépatite C Sans Interféron Patrick Marcellin

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’Hépatite C Sans Interféron Patrick Marcellin

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  1. Traitement de l’Hépatite C Sans Interféron Patrick Marcellin

  2. Hepatitis C

  3. Where we are: The achievements

  4. Hepatitis C: progress is accelerating The conclusion of the PHC 2009 • Cure = 100% in 10 years

  5. Progress is accelerating Earlier ? 2015 ?

  6. Where we areBetter understanding of therapeutic targets Protease Inhibitors NS5A Inhibitors Polymerase Inhibitors

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. Where we are: the limitations

  13. Where we are: limitations Insufficient screening Undiagnosed Pool2.5 million Undiagnosed Pool1.8 million Diagnosed Pool0.9 million Diagnosed Pool1.6 million

  14. Where we are: limitations Russia3M Korea1M US4M Europa5M Japan2M China43M Pakistan9M Egypt12M Vietnam7M India10M Brazil7M 170 million people HCV infected worldwide

  15. Where we are: limitations Insufficient access to treatment

  16. Where we are: limitations Access to treatment: the bottle necks Diagnosed Managed Treated Cured

  17. 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

  18. Where we are: The hope is becoming reality

  19. Ideal Therapy • 100% efficacy • IFN-free • All oral • Short duration • No resistance • Pan-genotypic • Well tolerated and safe • Low cost

  20. 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

  21. 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

  22. IFN-free ongoing trials: summary

  23. 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

  24. 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

  25. Where we go: IFN free Therapy

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. The Proof of Concept 100% efficacy All oral IFN-free Short duration No resistance Pan-genotypic Well tolerated and safe Low cost ? ?

  35. Hepatitis C: progress is accelerating The conclusion of the PHC 2009 • Cure = 100% in 2-3 years • One pill a day

  36. Where we are: limitations Insufficient access to treatment

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