1. Andrew J. Muir, MD Chief, Division of Gastroenterology Associate Professor of Medicine Department of Medicine Director, Gastroenterology/Hepatology Research Duke Clinical Research Institute Duke University School of Medicine Durham, North Carolina Best Practices in the Management of HCV in 2015 Supported by educational grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck, and ViiV.

2. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Disclosures Andrew J. Muir, MD, has disclosed that he has received funds for research support from AbbVie, Achillion, Bristol- Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hologic, Intercept, Janssen, Merck, NGM Biopharm, and Roche and consulting fees from AbbVie, Achillion, Bristol-Myers Squibb, Gilead Sciences, Intercept, Janssen, Lumena, Merck, Regulus Therapeutics, Salix, and Theravance.

3. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium About These Slides  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

4. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Aims  The rationale for HCV treatment  Treatment of genotypes 1-4  Future directions

5. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium AASLD/IDSA: When and in Whom to Initiate HCV Therapy  ALL pts are candidates for HCV therapy, regardless of disease stage  In regions where limited resources preclude treatment of all pts, the following groups should be prioritized for therapy: –Highest Priority (based on highest risk for disease complications) –Advanced fibrosis (F3) or compensated cirrhosis (F4) –Organ transplant –Type 2 or 3 essential mixed cryoglobulinemia with end-organ manifestations –Proteinuria, nephrotic syndrome, or membranoproliferative glomerulonephritis –High Priority (based on high risk for disease complications) –HIV-1 coinfection –Fibrosis (Metavir F2) –HBV coinfection –Debilitating fatigue AASLD/IDSA. HCV Management. http://www.hcvguidelines.org. –Other coexistent liver disease (eg, NASH) –Type 2 DM (insulin resistant) –Porphyria cutanea tarda

6. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium 1. van der Meer AJ, et al. JAMA. 2012;308:2584-2593. 2. van der Meer AJ. Expert Rev Gastroenterol Hepatol. 2015;9:559-566. 3. Younossi Z, et al. Clin Gastroenterol Hepatol. 2014;12:1349-1359. HCV Treatment Improves Health  Advanced fibrosis –Multicenter study [1] –5 hospitals (Europe, Canada) –530 pts with HCV –IFN regimens 1990-2003 –Advanced fibrosis or cirrhosis –Median follow-up: 8.4 yrs  Early-stage disease –Extra-hepatic manifestations [2] –Health-related quality of life [3] 30 20 10 All cause mortality Liver-related mortality or transplant HCC 10-Yr Cumulative Incidence [1] 0 26 8.9 1.9 27.4 5.1 21.8 SVR No SVR Percent

7. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Health Outcomes With DAA Treatment in Genotype 1 HCV Infection  TURQUOISE-II: OBV/PTV/RTV + DSV + RBV for 12 or 24 wks in pts with GT1 HCV and cirrhosis –Post hoc analysis, SVR12 associated with improved noninvasive fibrosis estimates, AFP levels, and surrogate markers of liver function 48 wks after treatment [1]  Modeling outcomes with DAA regimens –OBV/PTV/RTV + DSV ± RBV (vs no treatment) associated with reduced liver morbidity over lifetime horizon regardless of baseline fibrosis score (Markov model) [2] –LDV/SOF associated with lowest incidence of disease progression (including decompensation, HCC, liver transplantation, death) vs comparator regimens* (decision-analytic Markov model) [3] 1. Wedemeyer H, et al. EASL 2015. Abstract P0808. 2. Johnson SJ, et al. EASL 2015. Abstract P0850. 3. Younossi ZM, et al. AASLD 2014. Abstract 1754. *Comparator regimens: SOF + PR; SMV + PR; SMV + SOF; SMV + SOF + RBV; SOF + RBV; BOC + PR; No treatment

8. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Benefits of Early vs Delayed Treatment  Retrospective analysis of pts with HCV infection in VA Clinical Case Registry [1] –Early vs delayed treatment associated with reduced risk of liver-related events and death –Risk of delaying treatment increases as disease severity increases, due to diminished likelihood of achieving SVR  Markov disease utility state-transition modeling of OBV/PTV/RTV + DSV ± RBV therapy in genotype 1 HCV infection [2] –Treatment prolongs survival and quality of life vs watchful waiting –Treatment-related survival benefits of previously treated pts 1% to 6% lower than treatment-naive pts 1. McCombs J, et al. EASL 2015. Abstract O003. 2. Johnson S, et al. EASL 2015. Abstract P0806.

9. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Sofosbuvir + ribavirin ± pegIFN Ledipasvir/ sofosbuvir Simeprevir + sofosbuvir Ombitasvir/ paritaprevir/ ritonavir + dasabuvir 2015 Agents Sofosbuvir + daclatasvir

10. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 1 HCV Agents Protease Inhibitors Polymerase Inhibitors NS5A Inhibitors Other NucleotideNonnucleoside SimeprevirSofosbuvirLedipasvirRibavirin Paritaprevir/ ritonavir DasabuvirOmbitasvir Daclatasvir www.hcvguidelines.org

11. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Key Data for HCV decisions  HCV treatment history –Interferon and ribavirin regimen? –Protease inhibitor? Sofosbuvir?  Fibrosis stage? –Options for fibrosis assessment –If cirrhosis, is it decompensated? Child Pugh B or C? Transplant evaluation? http://www.hcvguidelines.org

12. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 1 HCV: FDA-Approved Regimens RegimenApproval for Genotype 1 Simeprevir + peginterferon + ribavirin*24-48 wks Sofosbuvir + peginterferon + ribavirin12 wks Sofosbuvir + ribavirin Interferon ineligible, 24 wks; HCC awaiting transplant, up to 48 wks Ledipasvir/sofosbuvir8-24 wks Ombitasvir/paritaprevir/ritonavir, dasabuvir, ± ribavirin 12-24 wks Simeprevir + sofosbuvir12-24 wks http://www.accessdata.fda.gov/scripts/cder/drugsatfda/ *Screening pts with genotype 1a HCV infection for NS3 Q80K polymorphism strongly recommended and alternative therapy should be considered if Q80K detected.

13. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 1 HCV: AASLD/IDSA- Recommended Regimens RegimenGenotype 1Regimen Features Simeprevir + peginterferon + ribavirin Not recommendedQD-QWK; multiple tablets + injection Sofosbuvir + peginterferon + ribavirin Not recommended QD-QWK; multiple tablets + injection Sofosbuvir + ribavirinNot recommendedQD; multiple tablets Ledipasvir/sofosbuvirRecommendedQD; single-tablet regimen Ombitasvir/paritaprevir/ritonavir, dasabuvir, ± ribavirin RecommendedQD-BID; multiple tablets Simeprevir + sofosbuvir ± ribavirinRecommendedQD; multiple tablets http://www.hcvguidelines.org

14. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 1 HCV Treatment Naive  AASLD-IDSA guidelines –3 regimens recommended Ledipasvir/ Sofosbuvir* Ombitasvir/ Paritaprevir/ Ritonavir + Dasabuvir Simeprevir + Sofosbuvir Genotype 1a, no cirrhosis12 wks12 wks + RBV12 wks ± RBV Genotype 1a, cirrhosis12 wks24 wks + RBV24 wks ± RBV Genotype 1b, no cirrhosis12 wks Genotype 1b, cirrhosis12 wks12 wks + RBV24 wks http://www.hcvguidelines.org *Ledipasvir/sofosbuvir for 8 wks can be considered in naive, noncirrhotic pts with baseline HCV RNA < 6 million IU/mL.

15. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 1 HCV Treatment Naive Noncirrhotic RegimenWksStudySVR Ledipasvir/sofosbuvir (HCV RNA < 6 M IU/mL) 8ION-3 [1,2] 119/123 (97%) Ledipasvir/sofosbuvir12ION-3 [1] 206/216 (95%) Simeprevir + sofosbuvir*8-12OPTIMIST-1 [3] 8 wks: 128/155 (83%) 12 wks: 150/155 (97%) Ombitasvir/paritaprevir/ritonavir, dasabuvir (GT1b) 12PEARL III [4] 207/209 (99%) Ombitasvir/paritaprevir/ritonavir, dasabuvir, ribavirin (GT1a) 12PEARL IV [4] 97/100 (97%) Sofosbuvir + daclatasvir12AI444040 [5] 41/41 (100%) 1. Kowdley K, et al. N Engl J Med. 2014;370:1879-1888. 2. Ledipasvir/sofosbuvir [package insert]. 3. Kwo PY, et al. EASL 2015. Abstract LP14. 4. Ferenci P, et al. N Engl J Med. 2014;370:1983-1992. 5. Sulkowski M, et al. N Engl J Med. 2014;370:211-221. *GT1a + Q80K-8 wks: 36/49 (73%); GT1a + Q80K-12 wks: 44/46 (96%).

16. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 1 HCV PegIFN/RBV Treatment Experienced  AASLD-IDSA guidelines –3 regimens recommended Ledipasvir/ Sofosbuvir Ombitasvir/ Paritaprevir/ Ritonavir + Dasabuvir Simeprevir + Sofosbuvir Genotype 1a, no cirrhosis12 wks12 wks + RBV12 wks ± RBV Genotype 1a, cirrhosis24 wks 12 wks + RBV 24 wks + RBV24 wks ± RBV Genotype 1b, no cirrhosis12 wks 12 wks ± RBV Genotype 1b, cirrhosis24 wks 12 wks + RBV 24 wks ± RBV http://www.hcvguidelines.org

17. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 1 HCV Previous PI Failure  AASLD-IDSA guidelines –1 regimen recommended Ledipasvir/ Sofosbuvir Ombitasvir/ Paritaprevir/ Ritonavir + Dasabuvir Simeprevir + Sofosbuvir ± Ribavirin Genotype 1a, no cirrhosis12 wksNone Genotype 1a, cirrhosis24 wks 12 wks + RBV None Genotype 1b, no cirrhosis12 wksNone Genotype 1b, cirrhosis24 wks 12 wks + RBV None http://www.hcvguidelines.org

18. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 1 HCV Previous PI Failure RegimenCirrhosisWksStudySVR Ledipasvir/sofosbuvirNo12ION-2 [1] 50/52 (96%) Ledipasvir/sofosbuvirYes24ION-2 [1] 14/14 (100%) Ledipasvir/sofosbuvirYes24SIRIUS [2] 75/77 (97%) Ledipasvir/sofosbuvir, ribavirinYes12SIRIUS [2] 74/77 (96%) Sofosbuvir + daclatasvirMix24AI444040 [3] 21/21 (100%) Sofosbuvir, daclatasvir, ribavirinMix24AI444040 [3] 19/20 (95%) 1. Afdhal N, et al. N Engl J Med. 2014;370:1483-1493. 2. Bourlière M, et al. Lancet Infect Dis. 2015;15:397- 404. 3. Sulkowski M, et al. N Engl J Med. 2014;370:211-221.

19. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium TURQUOISE II: OBV/PTV/RTV + DSV + RBV in Cirrhotic Pts With GT1 HCV  Pts (N = 380): –Treatment-naive and experienced pts –All compensated cirrhosis  Design –Open-label phase III  Regimen –Paritaprevir/ritonavir, dasabuvir, ombitasvir, ribavirin –Duration: 12 vs 24 wks Safety Outcome 12 Wks (n = 208) 24 Wks (n = 172) SAE, n (%)13 (6.2)8 (4.7) AE leading to d/c, n (%) 4 (1.9)4 (2.3) Fatigue, %32.746.5 Headache, %27.930.8 Poordad F, et al. N Engl J Med. 2014;370:1973-1982.

20. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium SIRIUS: LDV/SOF in Pts With GT1 HCV and Previous PegIFN/RBV ± PI Failure  Pts: –Treatment-experienced, failure of both pegIFN/RBV and PI + pegIFN/RBV regimens –Compensated cirrhosis  Design –Randomized, double-blinded  Regimens –Placebo 12 weeks followed by LDV/SOF + RBV for 12 wks –LDV/SOF + Placebo for 24 wks  2 AEs higher with LDV/SOF vs placebo during first 12 wks –Headache: 35% vs 21% –Fatigue: 17% vs 4% 75 77 Safety Outcome, % Placebo 12 wks Then LDV/SOF + RBV 12 wks (n = 78) LDV/SOF 24 wks (n = 77) SAE510 AE leading to d/c 10 Headache2740 Fatigue919 Bourlière M, et al. Lancet Infect Dis. 2015;15:397-404.

21. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205834s001lbl.pdf. http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/205123s008lbl.pdf. Update to sofosbuvir and ledipasvir/sofosbuvir US package inserts Update to simeprevir US package insert LDV/SOF. simeprevir.

22. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium LDV/SOF + RBV in Pts With Genotype 1 HCV and Previous Sofosbuvir Failure  Pts –GT1 treatment-experienced pts who experienced failure of prior SOF regimens (n = 51) –SOF + pegIFN/RBV: 49% –SOF + RBV: 39% –SOF placebo + pegIFN/RBV: 10% –GS-0938 monotherapy: 2% –16% black –59% GT1a –27% cirrhosis  Design –Open-label cohort  Regimen –Ledipasivr/sofosbuvir + RBV for 12 wks  1 pt relapsed: genotype 3a Wyles D, et al. Hepatology. 2015;[Epub ahead of print]. Wyles DL, et al. AASLD 2014. Abstract 235. Prior RegimenSVR12, n/N (%) PegIFN/RBV/ SOF 25/25 (100) SOF/RBV19/20 (95)

23. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotypes 2 and 3  AASLD-IDSA guidelines Genotype 2Sofosbuvir + RibavirinPeginterferon-α, Ribavirin + Sofosbuvir Treatment naive12 wks (16 wks for cirrhosis) None PegIFN/RBV nonresponders12-16 wks12 wks (alternative) http://www.hcvguidelines.org Genotype 3Sofosbuvir + RibavirinPeginterferon-α, Ribavirin + Sofosbuvir Treatment naive24 wks12 wks (alternative) PegIFN/RBV nonresponders24 wks12 wks (alternative)

24. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Treatment Naive Treatment Experienced BOSON: SVR12 With SOF-Based Regimens in GT3 by Tx History and Cirrhosis Status Foster GR, et al. EASL 2015. Abstract LO5. 58/ 70 65/ 72 68/ 71 12/ 21 18/ 22 21/ 23 26/ 34 17/ 36 30/ 35 44/ 54 49/ 52 41/ 54 No CirrhosisCirrhosisNo CirrhosisCirrhosis 83 90 96 57 82 91 76 82 94 47 77 86 100 80 60 40 20 0 SVR12 (%) SOF + RBV 16 wksSOF + RBV 24 wksSOF + PegIFN/RBV 12 wks n/N =

25. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Sofosbuvir + PegIFN/RBV or RBV in Pts With GT3 HCV and Previous SOF Failure  Pts –SOF + RBV treatment failures from FISSION, POSITRON, FUSION –Cirrhosis included  Design –Open-label cohorts –Pt/investigator selected regimen  Regimen –Sofosbuvir + ribavirin for 24 wks –PegIFN/RBV + sofosbuvir for 12 wks Esteban R, et al. EASL 2014. Abstract O8. n/N = 100 80 60 40 20 0 91 63 20/ 22 24/ 38 SVR12 (%)SOF + PegIFN/ RBV SOF + RBV

26. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium 0 LDV/SOF + RBV in Treatment-Experienced Pts With Genotype 3 HCV  Ledipasvir/sofosbuvir? –No data in sofosbuvir failure  Pts: –Treatment naive and experienced –With and without cirrhosis  Design –Open-label cohorts  Regimen –Ledipasvir/sofosbuvir + RBV for 12 wks Gane E, et al. EASL 2014. Abstract O6. Gane E, et al. AASLD 2014. Abstract LB-11. n/N = 100 80 60 40 20 NaiveNo Cirrhosis Cirrhosis 100 89 73 26/ 26 25/ 28 16/ 22 SVR12 (%)

27. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Daclastavir + Sofosbuvir in Tx-Naive and Tx-Exp’d Pts With Genotype 3 HCV ALLY-3 [1]  Pts: –Treatment naive and experienced –Prior sofosbuvir and alisporivir included –Prior NS5A inhibitors excluded –Cirrhosis: 21%  Design –2 open-label cohorts –Phase III  Regimen –Daclatasvir + sofosbuvir once daily for 12 wks  EASL recommendations for DCV + SOF in GT3 [2] –No cirrhosis: DCV + SOF for 12 wks –Compensated cirrhosis: DCV + SOF + RBV for 24 wks 1. Nelson DR, et al. Hepatology. 2015;61:1127-1135. 2. EASL HCV Guidelines. April 2015. 73 75 32 34 No Cirrhosis Cirrhosis SVR12 (%)NaiveExperienced 97 58 94 69 0 100 80 60 40 20

28. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 4 HCV Treatment Experienced RegimenWks FDA Approved AASLD/IDSAStudySVR12 Sofosbuvir + pegIFN/RBV 12YesRecommendedNEUTRINO [1] 27/28* (96%) Sofosbuvir + ribavirin24NoRecommendedRuane et al 2] 13/15 (87%) Ledipasvir/sofosbuvir12NoRecommendedMultiple [3,4] 19/20 †[3] ; 20/22 [4] (91-95%) Ombitasvir/paritaprevir/ ritonavir, ribavirin 12NoRecommendedPEARL-I [5] 49/49 (100%) 1. Lawitz E, et al. N Engl J Med. 2013;368:1878-1887. 2. Ruane PJ, et al. J Hepatol. 2015;62:1040-1046. 3. Kapoor R, et al. AASLD 2014. Abstract 240. 4. Abergel A, et al. EASL 2015. Abstract O056. 5. Hézode C, et al. Lancet. 2015;[Epub ahead of print]. *Study included treatment-naive pts only. † Treatment-naive and treatment-experienced pts.

29. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Genotype 5/6 HCV Treatment Naive  AASLD-IDSA guidelines Recommended RegimenDuration Genotype 5 Sofosbuvir + ribavirin + peginterferon 12 wks Genotype 6 Ledipasvir/ sofosbuvir 12 wks Alternative RegimenDuration Genotype 5Peginterferon + ribavirin48 wks Genotype 6 Sofosbuvir + ribavirin + peginterferon 12 wks http://www.hcvguidelines.org

30. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Sofosbuvir + ribavirin Sofosbuvir + ledipasvir Simeprevir + sofosbuvir Paritaprevir/ ritonavir + dasabuvir + ombitasvir Sofosbuvir + GS-5816 Sofosbuvir + daclatasvir Grazoprevir + elbasvir Daclatasvir + asunaprevir + beclabuvir

31. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Future HCV Treatment: Shorter Duration With Triple-Drug Regimens  Pts –Treatment naive, genotype 1 (N = 60)  Design –Single-center, open-label, phase IIA trial  Regimens –12 wks of SOF + LDV –6 wks of SOF, LDV, GS-9669 –6 wks of SOF, LDV, GS-9451 Kohli A, et al. Lancet. 2015;385:1107-1113. 20/2019/20 n/N = SOF + LDV 20/2019/20 100 95 100 80 60 40 20 0 SVR12 (%) SOF + LDV + GS-9669 SOF + LDV + GS-9451 12 wks6 wks

32. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Tx Naive, No Cirrhosis Txt Naive, Cirrhosis Txt Exp’d, +/- Cirrhosis Tx Naive, No Cirrhosis Short-Duration Sofosbuvir/GS-5816 + GS-9857: Efficacy Results  All pts who did not achieve SVR12 relapsed  SVR12 rates for treatment-experienced pts: no cirrhosis, 68% (17/25 pts); cirrhosis, 60% (3/5 pts) Gane EJ, et al. EASL 2015. Abstract LP03. 6 Wks 100 80 60 40 20 0 SVR12 (%) 93 87 67 14/1513/1520/30 n/N = 4 Wks 27 4/15

33. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium UNITY-1: Efficacy of 12-Wk DCV/ASV/BCV in Noncirrhotic GT1 by Treatment Experience Treatment-Naive PtsTreatment-Experienced Pts 100 80 60 40 20 0 SVR12 (%) AllGT1aGT1b 92 90 98 287/ 312 206/ 229 81/ 83 AllGT1aGT1b 92/ 103 64/ 75 28/ 28 89 85 100 Poordad F, et al. JAMA. 2015;313:1728-1735. n/N =

34. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium C-SWIFT: Short-Duration GZR/EBV + SOF in GT1 or 3 HCV Infection  Pts: treatment-naive, genotype 1 (n = 102) or genotype 3 (n = 41)  Design: multicenter, open-label, phase II trial  Regimen: grazoprevir/elbasvir FDC + sofosbuvir –GT1 noncirrhotic: 4 vs 6 wks; cirrhotic: 6 vs 8 wks –GT3 noncirrhotic: 8 vs 12 wks; cirrhotic: 12 wks Poordad F, et al. EASL 2015. Abstract O006. SVR12 (%) 100 80 60 40 20 0 4 Wks 6 Wks 8 Wks 12 Wks Genotype 1Genotype 3 33 26/ 30 16/ 20 17/ 18 14/ 15 14/ 14 10/ 11* 87 80 94 93 100 91 10/ 30* *Excluded pts who discontinued due to reasons other than virologic failure. Noncirrhotic Cirrhotic n/N =

35. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium C-EDGE: Grazoprevir/Elbasvir for Tx-Naive and Tx-Experienced Pts 1. Zeuzem Z, et al. EASL 2015. Abstract G07. 2. Kwo P, et al. EASL 2015. Abstract P0886. Tx-Naive: Grazoprevir/Elbasvir for 12 Wks in GT1, 4, or 6 HCV [1] SVR12 (%) All PtsGT1aGT1bGT4GT6 95 92 99 100 80 299/ 316 144/ 157 129/ 131 18/ 18 8/ 10 n/N = 100 80 60 40 20 0 Tx-Exp’d: Grazoprevir/Elbasvir ± RBV for 12 or 16 Wks in GT1, 4, or 6 HCV [2] 0 100 80 60 40 20 GZR/ EBV GZR/EBV + RBV GZR/ EBV 92 97/ 105 98/ 104 97/ 105 103/ 106 94 97 92 12 Wks 16 Wks

36. clinicaloptions.com 25th Annual CCO HIV and Hepatitis C Symposium Sofosbuvir + ribavirin Sofosbuvir + ledipasvir Simeprevir + sofosbuvir Paritaprevir/ ritonavir + dasabuvir + ombitasvir Sofosbuvir + GS-5816 Sofosbuvir + daclatasvir Grazoprevir + elbasvir Daclatasvir + asunaprevir + beclabuvir Many other DAA combinations currently under investigation

37. Go Online for More CCO Content on HCV Management! Video Modules featuring case-based expert roundtable discussions of key HCV management issues Additional downloadable PowerPoint slides on other important HCV topics, including strategies for managing challenging patient populations and areas of unmet need in HCV infection clinicaloptions.com/hepatitis