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Update on the HCV Antiviral Pipeline

Update on the HCV Antiviral Pipeline. Todd S. Wills, MD SPNS HCV Treatment Expansion Initiative Evaluation and Technical Assistance Center Infectious Disease Specialist. HCV Response Rates in HIV+ and HIV- Patients Treated With PegIFN /RBV. APRICOT HIV Positive Overall SVR: 40%. PRESCO

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Update on the HCV Antiviral Pipeline

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  1. Update on the HCV Antiviral Pipeline Todd S. Wills, MD SPNS HCV Treatment Expansion Initiative Evaluation and Technical Assistance Center Infectious Disease Specialist

  2. HCV Response Rates in HIV+ and HIV- Patients Treated With PegIFN/RBV APRICOT HIV Positive Overall SVR: 40% PRESCO HIV Positive Overall SVR: 50% FRIED HIV Negative Overall SVR: 56% 100 76 80 72 62 60 46 Patients With SVR (%) 36 40 29 20 176 95 191 152 298 140 n = 0 GT1/4 GT2/3 GT1/4 GT2/3 GT1/4 GT2/3 48 Wks of Therapy,600 mg RBV 24, 48, or 72 Wks of Therapy,Weight-Based RBV 48 Wks of Therapy,Weight-Based RBV Soriano V, et al. Care of patients coinfected with HIV and hepatitis C virus: 2007 updated recommendations from the HCV–HIV International Panel AIDS. 2007;21:1073-1089.

  3. Potential HCV antiviral targets C E1 E2/NS1 NS2 NS3 NS4A NS4B NS5A NS5B 5’ 3’ Internal ribosomal entry site RNA binding site Envelope glyco- proteins Signal peptide Serine protease/ helicase RNA dependent RNA polymerase telaprevir, boceprevir

  4. Response Terminology

  5. Adherence • Triple therapy presents challenges with already busy schedules[143] • TID dosing • Food requirements • Data show pegIFN/RBV adherence decreases over time[5] • Addition of PIs may exacerbate this trend 1. Telaprevir [package insert]. May 2011. 2. Boceprevir [package insert]. May 2011. 3. EMA. Boceprevir [package insert] 2011.4. EMA. Telaprevir [package insert] 2011. 5. Lo Re V 3rd, et al. Ann Intern Med. 2011;155:353-360. from Clinical Care Options

  6. Study 110: High Rates of Early Response With TVR + PR in Coinfected Patients • Similar efficacy results observed with or without concurrent ART • Nausea, pruritus, dizziness, fever more common with TVR vs placebo • Pharmacokinetic interactions with ATV or EFV not clinically significant Undetectable HCV RNA, Week 4 (ITT) Undetectable HCV RNA, Week 12 (ITT) No ART ATV/RTV-based ART EFV-based ART Total 100 100 75 75 71 71 80 80 70 68 64 57 60 60 Undetectable HCV RNA (%) Undetectable HCV RNA (%) 40 40 17 14 12 20 12 12 20 5 0 0 0 0 12/16 9/14 26/37 5/7 0/6 1/8 0/8 1/22 12/16 8/14 25/37 n/N = 5/7 1/6 1/8 1/8 3/22 n/N = Telaprevir + PR PR Telaprevir + PR PR Sulkowski M, et al. CROI 2011. Abstract 146LB.

  7. Study 110 – SVR 12 Data Dieterich D, et al. CROI 2012 Abstract 46

  8. Telaprevir plus PegINF and Ribavirin in HIV/HCV Infected Patients – Side Effects *no cases of severe rash Sherman, KE et al.. AASLD Conference November 2011 – Late Breaker Abstract 8

  9. Boceprevir in Addition to Pegylated INF alfa 2a in HIV/HCV Patients on ARVs Sulkowski, M. CROI 2012 Abstract 47

  10. Investigational Agents

  11. PSI-7977 – Phase II Trial Data HCV uridine nucleotide analogue Genotype 1 Genotype 2/3 Lawritz, E. et al. J of Hepatology 54 (s1) 2012

  12. TMC-435 – Phase IIb trial data • HCV NS3/4A Protease Inhibitor (Once-Daily) • Prior Treatment Failures 100 mg Zeuzem S., et al. J of Hepatology 54 (s1) 2012 150 mg P<0.001 vs placebo

  13. Interferon Sparing Strategies • ABT 450/r – ritonovir boosted HCV PI + • ABT 072 – HCV polymerase inhibitor + • Weight-based ribavirin • Open label 12 week treatment trial 11 patients • Interferon sparing • 91% SVR24 • One patient relapsed 8 weeks post Rx • All patients were IL28B CC Lawitz, E. et al. Of Hepatology 56(s1) 2012

  14. Interferon AND Ribavirin Sparing Strategies • Daclatasvir (NS5A replication complex inhibitor) + • Asunaprevir (HCV NS3 PI) • Open label trial of both drugs in 43 prior null responders or with IFN/R intolerance Suzuki, F. et al. J of Hepatology 56 (s1) 2012

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