Robert G. Knodell, M.D. Maryland Chapter, American College of Physicians Fb February 3, 2012

Transcription

1 Treatment of Hepatitis C:Present and Future Robert G. Knodell, M.D. Scientific Meeting Maryland Chapter, American College of Physicians Fb February 3, 2012

2 Presentation Objectives Appreciate the Public Health Significance of Chronic Hepatitis ii C Infection Understand Strategies and Goals of Hepatitis C Management Be Familiar with ihcurrent and Projected dfuture Drug Regimens for Hepatitis C Treatment

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7 Evolving Response Definitions in Patients Receiving i HCV Therapy With DAAs Term Time Point HCV RNA Level RVR NEW: ervr Wk 4 of therapy NEW: Wk 4 of triple therapy Wk 4 and later time point Undetectable Undetectable EVR Wk 12 of therapy Undetectable (complete EVR) ETR End of therapy Undetectable SVR 6 mos posttherapy Undetectable 2 log decrease from baseline (partial EVR) Adapted from Ghany MG, et al. Hepatology. 2009;49:

8 Progress in Therapy of Hepatitis C: SVR 80% 70% 70% 60% 54% 50% 40% 30% 20% 10% 0% 10% 42% 39% 16% IFN N6 6 m IFN 12 m IFN/RBV 12 m PegIFN 12m Sustatined Virologic Response PegIFN/RBV 12m HCV CV-PI/PegIFN/RBV V GT1 IFN: Interferon PegIFN: pegylated IFN RBV: Ribavirin PI: protease inhibitor

9 HCV Genome and Gene Products Potential Targets for Direct Acting Antiviral Agents TenCate V, et al. Hepat Med. 2010;2: Protease Inhibitors: boceprevir; telaprevir

10 Boceprevir and Telaprevir Boceprevir, a potent inhibitor of Boceprevir HCV NS3/4A protease SPRINT 2: naive GT1 patients Telaprevir, a potent inhibitor of HCV NS3/4A protease RESPOND 2: nonresponder GT1 patients t (partial responders and relapsers) Both tested in combination with standard of care pegifn alfa Telaprevir 2/RBV in phase III studies in ADVANCE: naivegt1 patients chronic HCV infection ILLUMINATE: response guided therapy in naive GT1 paitents REALIZE: nonresponder GT1 patients (null responders, partial responders, relapsers)

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16 SVR Rates With BOC and TPV in GT1 Treatment Ni Naive and Experienced E i dpts 100 Current Standard d of Care 100 SOC + Protease Inhibitors (Approval Anticipated in 2011) [1-2] [3-4] [3-4] SVR (%) SVR (%) [1-2] [3-4] 20 0 Treatment-Naive Pts Treatment- Experienced 0 Treatment-Naive Pts Treatment- Experienced 1. Poordad F, et al. AASLD Abstract LB Jacobson IM, et al. AASLD Abstract Bacon BR, et al. AASLD Abstract Foster GR, et al. APASL Abstract 1529.

17 Adverse Events Reported More Frequently With TVR and BOC vs PegIFN/RBV Telaprevir [1] Adverse Event, % TVR-Containing Arms (n = 727) PegIFN/RBV Arm (n = 361) Pruritus Nausea Rash Anemia Diarrhea Boceprevir [2] Adverse Event, % BOC-Containing Arms (n = 734) PegIFN/RBV Arm (n = 363) Anemia Dysgeusia Jacobson IM, et al. AASLD Abstract Poordad F, et al. AASLD Abstract LB4.

18 Direct Acting Antivirals for Hepatitis C Nature Reviews Drug Discovery 10, (February 2011) doi: /nrd3361

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22 Direct Acting Antivirals for Hepatitis C Nature Reviews Drug Discovery 10, (February 2011) doi: /nrd3361

23 Summary Hepatitis C Will Continue To Be A Significant Medical Problem In The United States For Years To Come Addition OF NS3 Protease Inhibitors To Interferon And Ribivirin Has Resulted In Significant Improvement In Hepatitis C Cure Rates (SVR) Albeit Some Genotype l Treatment Groups (Partial, Null Responders) Continue To Resist Cure Exciting, More Effective and Expensive Therapeutic Agents For Treatment Of Hepatitis C Will Soon Be Available; The Holy Grail Of Hepatitis C Treatment (No Interferon!) Looms On The Horizon

24 IL28B Genetic Variation and Viral Clearance: Distribution by CaucasianAmericans African Americans Race/Ethnicity Hispanic Americans Thompson A, et al. Presented at AASLD, 2009 Oct 29 Nov 2, 2009; Boston, MA. Oral Presentation LB5. Ge D, et al. Nature. 2009;461: TT CT CC

25 IL28B Genetic Variation and Viral Clearance: Results A polymorphism on chromosome 19, rs (T/T, T/C, or C/C), was strongly associated with ihsvr in all patient groups. Ge D, et al. Nature. 2009;461:

26 SVR according to IL28B genotype in Boceprevir and Telaprevir Naïve Trials CC CT TT SVR % PR BOC RGT BOC 48 PR T8 PR T12PR SPRINT 2 ADVANCE Poordad, ddet al. NEJM 2011 Jacobson, et al. NEJM 2011 Slide courtesy of Dr. Tim Morgan