Interferon free HCV Therapy: Are we getting there?

Transcription

1 Interferon free HCV Therapy: Are we getting there? Heiner Wedemeyer Hannover Medical School Germany 1

2 Disclosures Honoraria for consulting or speaking (last 5 years): Abbott, Biolex, BMS, Boehringer Ingelheim, Gilead, ITS, JJ/Janssen Cilag, Merck/Schering Plough, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, ViiV Research grants: Abbott, BMS, Gilead, Merck, Novartis, Roche, Roche Diagnostics, Siemens and almost all presenters during this meeting will have similar disclosures. So, there is quite some interest supporting the answer

3 Interferon free HCV Therapy: Are we getting there? YES! and much sooner than most of us would have expected!

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5 Interferon free HCV Therapy: Are we getting there? YES! but

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7 Interferon free HCV Therapy: Are we getting there? YES! but, But, come on Graham

8 Let s talk about something different Other Old fashion Antacids Proton pump inhibitors

9 What are the facts?

10 HCV HCV HIV HBV

11 Immune Control of HCV Is Possible! Spontaneous clearance of acute hepatitis C in 10% 50% of cases

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13 Immune Control of HCV Is Possible! Spontaneous clearance of acute hepatitis C in 10% 50% of cases HCV specific T cell responses are associated with recovery from acute hepatitis C; NK cells contribute to clearance of HCV SVR means CURE!

14 Long Term follow up after treatment of chronic hepatitis C: Sustained SVR in >98% of cases

15 No cases of HCV reactivation during immunosuppressive treatments! (in contrast to HBV infection )

16 Is cure with DAAs alone also possible in the absence of a functional immune system?

17 Is cure with DAAs alone also possible in the absence of a functional immune system? In vitro? YES!

18 Combination therapy with a protease inhibitor and a non nuc NS5B inhibitor can clear hepatoma cells from their HCV replication VX950 MK VX950 + MK Vliegen et al., J Hepatol 2009

19 Is cure with DAAs alone also possible in the absence of a functional immune system? In vivo? YES!

20 PI + low dose Pol Inh PI + Pol Inh + IFNa Ohara et al., J Hepatol 2011

21 PI + low dose Pol Inh PI + Pol Inh + IFNa Ohara et al., J Hepatol 2011

22 PI + high dose Pol Inh = Cure w/o IFNa in immunodeficient mice! Ohara et al., J Hepatol 2011

23 Interferon free HCV Therapy: Are we getting there? Emerging Clinical Data!

24 Antiviral Targets Against Hepatitis C Entry Inhibitors Ribavirin NS5A Inhibitors Protease Inhibitors Cyclophillin Inhibitors Polymeraseinhibitors NI NNI

25 Interferon free Combination Treatment Protease Inhi. Nukl. Polym. Inh. Non Nuc NS5A Inhib Cyclophilin Inhibitors Protease Inhi. X X X Nukl. Polym. Inhib. Non Nuc NS5A Inh x X Ribavirin x x x

26 SVR without interferon in Nullresponder: 2/9 genotype 1a 2/2 genotype 1b

27 Interferon free Combination Treatment GS RBV TMC435 + GS 7977 BI BI RBV Alisporivir +/ RBV Daclatasvir based: DAC + GS RBV DAC + Asunaprevir Telaprevir based: VX 222 ALS 2200 ABT 450r based: ABT450r + ABT RBV ABT450r + ABT RBV ABT450r + ABT RBV Gilead QUAD: GS GS GS RBV Genentech QUAD: DNVr + MCB + SBV + RBV

28 Interferon free Combination Treatment GS RBV ABT 450r based: TMC435 + GS 7977 BI BI RBV Alisporivir +/ RBV Daclatasvir based: DAC + GS RBV DAC + Asunaprevir Telaprevir based: VX 222 ALS 2200 ABT450r + ABT RBV ABT450r + ABT RBV ABT450r + ABT RBV Gilead QUAD: SVR Rates % with some combinations!!!! GS GS GS RBV Genentech QUAD: DNVr + MCB + SBV + RBV

29 What do I want? >95% SVR Once daily Very los frequency of adverse events Few drug drug interactions Pan genotypic Short, fixed duration (12 24 weeks) Affordable to everyone.

30 What are the timelines?? January 2013 TMC 435/PEG/RBV Genotype 1 SVR 24 April 2013 GS7977/PEG/RBV Genotype 1,4,5,6 SVR 12 October 2013 BMS790052/PEG/RBV Genotype 1 SVR 12 February 2014 BI201335/PEG/RBV Genotype 1 SVR 24 April 2013 GS7977/ RBV Genotype 2,3 SVR12

31 The probably most important point All oral therapy will lead to a change in treatment paradigm The number of treatable patients will dramatically increase! HCV infected patients Diagnosed patients Can be treated with IFNa Cured with IFNa

32 The probably most important point All oral therapy will lead to a change in treatment paradigm The number of treatable patients will dramatically increase! HCV infected patients Diagnosed patients Can be treated IFN-free Cured IFN-free

33 The probably most important point All oral therapy will lead to a change in treatment paradigm The number of treatable patients will dramatically increase! HCV infected patients Diagnosed patients Cured IFN-free

34 Treatment of Hepatitis C /5 Every hepatitis C patient can be cured w/o IFNa!