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Best of HCV From AASLD 2013

Best of HCV From AASLD 2013. Kimberly A. Brown, MD Detroit, Michigan, USA. This activity has been supported by an independent medical education grant from Bristol Myers Squibb .

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Best of HCV From AASLD 2013

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  1. Best of HCVFrom AASLD 2013 Kimberly A. Brown, MD Detroit, Michigan, USA This activity has been supported by an independent medical education grant from Bristol Myers Squibb . 2013 IC-HEP Educational supporters include Bristol Myers Squibb and Janssen Therapeutics EMEA.  Supporters do not influence IC-HEP faculty selection or educational content.

  2. Abstract #LB-1 Phase 2b study of the interferon-free and ribavirin-free combination of daclatasvir, asunaprevir, and BMS-791325 for 12 weeks in treatment-naïve patients with chronic HCV genotype 1 infection Gregory T. Everson1, Karen D. Sims2, Paul J. Thuluvath3, Eric Lawitz4, Tarek Hassanein5,Maribel Rodriguez-Torres6, Trevor Hawkins7, Howard Schwartz8, Vinod K. Rustgi9, Federico Hinestrosa10, James M. Levin11, Zobair M. Younossi12, Lynn R. Webster13, Timothy Eley2, Shu-Pang Huang14,Fiona McPhee15, Dennis M. Grasela2, David F. Gardiner2 1. University of Colorado Denver, Aurora, CO, United States. 2. Bristol-Myers Squibb, Hopewell, NJ, United States. 3. Mercy Medical Center, Baltimore, MD, United States. 4. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States. 5. Southern California Liver Centers, Coronado, CA, United States. 6. Fundación de Investigación, San Juan, Puerto Rico,United States. 7. Southwest CARE Center, Santa Fe, NM, United States. 8. Miami Research Associates, South Miami, FL, United States. 9. Metropolitan Research, Arlington, VA, United States. 10. Orlando Immunology Center, Orlando, FL, United States. 11. Dean Foundation for Health, Research and Education, Inc, Madison, WI, United States. 12. Inova Fairfax Hospital, Center for Liver Diseases,Falls Church, VA, United States. 13. CRI Lifetree, Salt Lake City, UT, United States. 14. Bristol-Myers Squibb, Princeton, NJ, United States. 15. Bristol-Myers Squibb, Wallingford, CT, United States.

  3. Direct-Acting Antiviral Agents • Daclatasvir (DCV) • NS5A replication complex inhibitor with potent, pan-genotypic activity in vitro • Studied in over 5500 patients • Asunaprevir (ASV) • NS3 protease inhibitor active against genotypes (GT) 1, 4, 5, and 6 in vitro • Studied in over 2000 patients • BMS-791325 • Non-nucleoside, NS5B polymerase inhibitor active against GT 1, 3, 4, 5, and 6 in vitro • Studied in over 500 patients Everson GT, et al. Abstract #LB-1, AASLD 2013

  4. Randomized, Phase 2b Open-Label Study (AI443-014) Primary endpoint: SVR12 DCV 30 mg BID + ASV 200 mg BID + BMS-791325 75 mg BID 12-week follow-up Additional follow-up to SVR48 N = 80 DCV 30 mg BID + ASV 200 mg BID + BMS-791325 150 mgBID N = 86 Week 12 24 0 • Patients: treatment-naive, stratified by GT 1a/1b and presence of biopsy-confirmed cirrhosis (82% GT1a and 9% cirrhotics). • Primary end point: HCV RNA < LLOQ 12 weeks post-treatment (SVR12) • Observed analysis: breakthrough, relapse, addition of pegIFNα/RBV = failure • Modified intent-to-treat analysis: missing, breakthrough, relapse or addition of pegIFNα/RBV = failure Everson GT, et al. Abstract #LB-1, AASLD 2013

  5. Efficacy Through SVR12 (Observed) 97.5 94.2 92.2 91.7 92.4 91.7 DCV + ASV + ‘325 75 mg DCV + ASV + ‘325 150 mg Response, % of patients 78/80 81/86 73/79 77/84 71/77 77/84 End of Treatment SVR4 SVR12 Everson GT, et al. Abstract #LB-1, AASLD 2013

  6. Safety Outcomes Everson GT, et al. Abstract #LB-1, AASLD 2013

  7. Conclusions The all oral, interferon and ribavirin-free combination of DCV, ASV and BMS-791325 in treatment naïve Genotype 1 resulted in overall SVR12 rates of 91.7-92.2% The combination was well tolerated with 1.1% of patients discontinuing treatment due to AE Excellent safety was observed with 1.6% of patients experiencing a serious AE with only 1 patient experiencing a Grade 3/4 AE during the study Everson GT, et al. Abstract #LB-1, AASLD 2013

  8. Abstract #76 High Efficacy and Safety of the All-Oral Combination Regimen, MK-5172/MK-8742 +/- RBV for 12 Weeks in HCV Genotype 1 Infected Patients: The C-WORTHY Study Eric Lawitz1, John M. Vierling2, Abel Murillo3, Marcelo Kugelmas4, Jan Gerstoft5, Peter Winkle6, Luis A. Balart7, Peer B. Christensen8, Reem H. Ghalib9, Ronald Nahass10, Melissa Shaughnessy11, Xiao Sun11, Peggy Hwang11, Janice Wahl11, Michael Robertson11, Barbara Haber11 1. University of Texas Health Science Center, Texas Liver Institute, San Antonio, TX, United States. 2. Baylor College of Medicine, Houston, TX, United States. 3. Advanced Intervention & Pain Management Research Clinic, Miami, FL, United States. 4. South Denver Gastroenterology, PC, Englewood, CO, United States. 5. Epidemiklinikken, Rigshospitalet, Copenhagen, Denmark. 6. Anaheim Clinical Trials, Anaheim, CA, United States. 7. Tulane University Medical Center, New Orleans, LA, United States. 8. Infektionsmed. Afd Q 2 sal, Odense Universitets Hospital, Odense, Denmark.

  9. Background MK-5172 is a selective inhibitor of hepatitis C virus NS3/4a protease which is effective across genotypes and resistant variants MK-8742 is an investigational HCV NS5A replication complex inhibitor Lawitz E, et al. Abstract #76, AASLD 2013

  10. Study Design Follow-up MK-5172 (100 mg) + MK-8742 (20 mg) + RBV; G1a & G1b n=25 Follow-up MK-5172 (100 mg) + MK-8742 (50 mg) + RBV; G1a & G1b n=27 Follow-up MK-5172 (100 mg) + MK-8742 (50 mg); G1b n=13 Genotype 1a and 1b treatment naïve, non-cirrhotic Lawitz E, et al. Abstract #76, AASLD 2013 TW12 SVR24 SVR4 SVR8 SVR12 TW4 D1

  11. Virologic Responses 13 13 25 25 25 27 13 13 24 25 25 27 13 13 13 13 24 25 24 27 24 25 24 27 Treatment Follow-up Lawitz E, et al. Abstract #76, AASLD 2013

  12. Common Adverse Events During Treatment* * Incidence ≥10% in all arms Lawitz E, et al. Abstract #76, AASLD 2013

  13. Conclusions 12 week treatment with a combination of MK-5172 and MK-8742 plus RBV resulted in high SVR 12 rates in GT 1a and 1b non-cirrhotic patients of 89-96% 12 week treatment with MK-5172 and MK-8742 without RBV resulted in a 100% SVR 12 in GT 1b non-cirrhotic patients Treatment overall was well tolerated with good safety Lawitz E, et al. Abstract #76, AASLD 2013

  14. Abstract #73 Once Daily Sofosbuvir/Ledipasvir Fixed Dose Combination with or without Ribavirin: the ELECTRON trial Edward J. Gane1, Catherine A. Stedman2, Robert H. Hyland3, Xiao Ding3, EvgueniaS. Svarovskaia3, Phil S. Pang3, William T. Symonds3 1. Auckland Clinical Studies, Auckland, New Zealand. 2. Christchurch Clinical Studies Trust, Christchurch, New Zealand. 3. Gilead Science, Inc, Foster City, CA, United States.

  15. Direct Acting Antiviral Agents Sofosbuvir/LedipasvirFDC • Once daily, oral fixed-dose (400/90 mg) combination tablet • No food effect • >2000 patients treated SOF Nucleotide Polymerase inhibitor LDV NS5A inhibitor GS-9669 HCV NS5B non-nucleoside inhibitor, binding at thumb site II of the polymerase Potent antiviral activity with QD dosing Nanomolar potency against GT 1a and 1b Gane EJ, et al. Abstract #73, AASLD 2013

  16. Study Design Wk 0 Wk 6 Wk 12 SOF/LDV FDC (n=10) F4 Randomized SOF/LDV FDC + RBV (n=10) GT 1 Experienced SVR12 SOF/LDV FDC + RBV (n=25) F3/F4 Randomized SOF/LDV FDC + GS-9669 (n=25) GT 1 Naïve SOF/LDV FDC + RBV (n=25) F0/F1/F2 Primary endpoint: SVR12 (HCV RNA <LLOQ) Patients enrolled in ELECTRON or ELECTRON 2 (GT1, F3/F4) All groups were open label Gane EJ, et al. Abstract #73, AASLD 2013

  17. SVR 12 Results: GT 1 Treatment-Experienced Patients with Advanced Fibrosis/Cirrhosis 7/10 9/9 25/25* 26/26* Duration (wk) 12 12 12 12 F4 only F3/F4 *From ELECTRON 2 Gane EJ, et al. Abstract #73, AASLD 2013

  18. SVR12 Results: Treatment DurationGenotype 1, Treatment-naïve, No Cirrhosis 25/25 21/21 17/25 † Duration (wk) 12 8 6 *Gane et al. EASL 2013. †Lawitz et al, Abstract #215, AASLD 2013 (LONESTAR)

  19. Conclusions In treatment-experienced patients with advanced fibrosis/cirrhosis, either RBV or GS-9669 may enhance the efficacy of SOF/LDV given for 12 weeks The optimal duration of SOF/LDV in treatment-naïve GT 1 patients, even with the addition of RBV, is more than 6 weeks Regimens of SOF/LDV alone, or with RBV or GS-9669, were safe and well tolerated Gane EJ, et al. Abstract #73, AASLD 2013

  20. Abstract #75 Interferon- and Ribavirin-free Regimen of ABT-450/r + ABT-267 in HCV Genotype 1b-infected Treatment-naïve Patients and Prior Null Responders Eric Lawitz1, Christophe Hezode2, Peter Varunok3, Paul J. Thuluvath4, Tolga Baykal5, Mudra Kapoor5, Sandra S. Lovell5, Tianli Wang5, Tami Pilot-Matias5, Regis A. Vilchez5, Barry Bernstein5 1. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States. 2. Assistance PubliqueHopitaux de Paris, Paris, France. 3. Premier Medical Group of the Hudson Valley, PC, Poughkeepsie, NY, United States. 4. The Institute for Digestive Health and Liver Disease at Mercy, Baltimore, MD, United States. 5. AbbVie Inc., North Chicago, IL, United States.

  21. Background and Aims ABT-450 is an HCV protease inhibitor (dosed with ritonavir 100 mg, ABT-450/r) ABT-267 is an NS5A inhibitor Both compounds have shown potent antiviral activity in vitro against HCV genotypes (GT) 1-4 and 6. Lawitz E, et al. Abstract #75, AASLD 2013

  22. PEARL-I Study Design PlannedN HCV Genotype/Regimen Treatment Experience Week 12 Week 24 BL Group 1 40 Group 2 40 Group 3 40 Group 4 40 Group 5 40 Group 6 40 Group 7 40 Group 8 40 GT4 ABT-450/r + ABT-267 Treatment-naïve GT1b ABT-450/r + ABT-267 Treatment-naïve Substudy 1: Patients Without Cirrhosis GT1b ABT-450/r + ABT-267 Null Responders GT4 ABT-450/r + ABT-267 + rbv Treatment-naïve GT4 ABT-450/r + ABT-267 Partial/Null Responders & Relapsers GT4 ABT-450/r + ABT-267 + rbv Partial/Null Responders & Relapsers Substudy 2: Patients With Compensated Cirrhosis GT1b ABT-450/r + ABT-267 Treatment-naïve GT1b ABT-450/r + ABT-267 Partial/Null Responders & Relapsers Lawitz E, et al. Abstract #75, AASLD 2013

  23. Efficacy: Treatment-Naïve Patients, ITT 100 97.6 97.6 95.2 100 80 60 Percentage of Patients (%) 40 20 42/42 41/42 41/42 40/42 0 Week 4 Week 12 (EOTR) SVR4 SVR12 Lawitz E, et al. Abstract #75, AASLD 2013

  24. Efficacy: Prior Null Responders, ITT 97.5 97.5 92.5 90.0 100 80 60 Percentage of Patients (%) 40 20 39/40 39/40 37/40 36/40 0 Week 4 SVR4 SVR12 Week 12 (EOTR) Lawitz E, et al. Abstract #75, AASLD 2013

  25. Treatment-Emergent Adverse Events (AEs) Occurring in >10% of Patients in Either Group Lawitz E, et al. Abstract #75, AASLD 2013

  26. Conclusions Treatment of both naïve and cirrhotic GT 1b patients with a combination of ABT 450/r and ABT 267 resulted in high SVR12 rates (95.2% and 90%) The combination was well tolerated with good safety Lawitz E, et al. Abstract #75, AASLD 2013

  27. Abstract #LB-4 Sofosbuvir in Combination With PegIFN and Ribavirin for 12 Weeks Provides High SVR Rates in HCV-Infected Genotype 2 or 3 Treatment Experienced Patients with and without Compensated Cirrhosis: Results from the LONESTAR-2 Study Eric Lawitz1, 2, Fred Poordad1, 2, Diana M. Brainard3, Robert H. Hyland3, Di An3, William T. Symonds3, John G. McHutchison3, Fernando E. Membreno1, 2 1. Texas Liver Institute, San Antonio, TX, United States. 2. University of Texas Health Science Center, San Antonio, TX, United States. 3. Gilead Science, Inc, Foster City, CA, United States.

  28. Study Design Wk 0 Wk 12 Wk24 Wk36 SOF + PEG/RBV GT 2/3(N=47) SVR12 • Study population • HCV GT 2 or 3 • Failed treatment with pegylated interferon and ribavirin • Approximately 50% with compensated cirrhosis • HIV and HBV coinfected patients excluded Lawitz E, et al. Abstract #LB-4, AASLD 2013

  29. Results: SVR12 by HCV Genotype SVR12 (%) 42/47 22/23 20/24 Overall GT 2 GT 3 Lawitz E, et al. Abstract #LB-4, AASLD 2013

  30. Results: SVR12 by Cirrhosis Status SVR12 (%) 9/9 13/14 10/12 10/12 Error bars represent 95% confidence intervals. Lawitz E, et al. Abstract #LB-4, AASLD 2013

  31. Results: Adverse Events Lawitz E, et al. Abstract #LB-4, AASLD 2013

  32. Conclusions Lawitz E, et al. Abstract #LB-4, AASLD 2013 • SOF + PEG/RBV for 12 weeks demonstrated high efficacy in treatment-experienced GT 2/3 patients who have historically low response rates and limited treatment options • SVR rates were similar in patients with and without cirrhosis • SOF + PEG/RBV was generally safe and well tolerated • Safety profile consistent with PEG/RBV treatment • Low discontinuation rates

  33. Abstract #215 Once Daily Sofosbuvir/Ledipasvir Fixed Dose Combination with or without Ribavirin Resulted in ≥95% Sustained Virologic Response In Patients with HCV Genotype 1, Including Patients with Cirrhosis: the LONESTAR trial Eric Lawitz1, Fred Poordad1, Robert H. Hyland2, Xiao Ding2, Christy Hebner2, Phil S. Pang2,William T. Symonds2, John G. McHutchison2, Fernando E. Membreno1 1. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States. 2. Gilead Science, Inc, Foster City, CA, United States.

  34. Study Design Wk 8 Wk 12 Wk20 Wk24 Wk 0 SVR12 SVR12 • Treatment Naïve(Nocirrhosis) SOF/LDV SVR12 COHORT 1 (n=60) SOF/LDV + RBV SVR12 Randomized 1:1:1 SVR12 SOF/LDV • PI Failures • (50% cirrhosis) SOF/LDV COHORT 2 (n=40) Randomized 1:1 SOF/LDV + RBV Lawitz E, et al. Abstract #215, AASLD 2013 • Single center study of GT 1 patients • Broad inclusion criteria • No upper limit to age or BMI • Platelets ≥50,000/mm3

  35. Results: Demographics of Patients Who Previously Failed PI Therapy Lawitz E, et al. Abstract #215, AASLD 2013 • All patients were required to have experienced virologic failure • Patients who stopped prior therapy due to an AE were excluded

  36. SVR12 Results Patients (%) 19/20 21/21 18/19 18/19 21/21 RBV ─ + ─ ─ + Duration (week) 8 8 12 12 12 Treatment Naïve (No Cirrhosis) PI Failures (50% Cirrhosis) Lawitz E, et al. Abstract #215, AASLD 2013

  37. Patients Who Previously Failed Protease Inhibitor Therapy: With and Without Cirrhosis Patients (%) 18/19 21/21 8/8 10/10 10/11 11/11 RBV ─ + ─ + ─ + 12 Duration (week) 12 12 Overall No Cirrhosis Cirrhosis Lawitz E, et al. Abstract #215, AASLD 2013

  38. Results: Safety Summary *Peptic ulcer, spinal compression fracture; †Delirium, suicidal ideation. Lawitz E, et al. Abstract #215, AASLD 2013

  39. Conclusions Lawitz E, et al. Abstract #215, AASLD 2013 Once daily SOF/LDV Fixed Dose Combination with or without RBV resulted in ≥95% SVR12 in patients with HCV GT 1, including patients with cirrhosis Patients with cirrhosis previously failing PI therapy had 100% SVR12 with the combination of SOF/LDV fixed dose combination with RBV for 12 weeks Similarly to prior reports, the combination was well tolerated with an excellent safety profile

  40. Abstract #LB-3 SVR results of a once-daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naïve and prior null responder patients: The COSMOS study Ira M. Jacobson1, Reem H. Ghalib2, Maribel Rodriguez-Torres3, Zobair M. Younossi4, Ana Corregidor5, Mark S. Sulkowski6, Edwin DeJesus7, Brian Pearlman8, Mordechai Rabinovitz9, Norman Gitlin10, Joseph K. Lim11, Paul J. Pockros12, Bart Fevery13, Tom Lambrecht14, Sivi Ouwerkerk-Mahadevan13, Katleen Callewaert13, William T. Symonds15, Gaston Picchio16, Karen Lindsay16, Maria Beumont-Mauviel13, Eric Lawitz17 1. Weill Cornell Medical College, New York, NY, United States. 2. Medicine and Gastroenterology and Hepatology, The Liver Institute, Dallas, TX, United States. 3. Fundación de Investigación, San Juan, Puerto Rico, United States. 4. Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, United States. 5. Borland-Groover Clinic, 4800 Belfort Rd, Jacksonville, FL, United States. 6. Johns Hopkins University School of Medicine, Baltimore, MD, United States. 7. Orlando Immunology Center, Orlando, FL, United States. 8. Atlanta Medical Center, Atlanta, GA, United States. 9. University of Pittsburgh Medical Center, Pittsburgh, PA, United States. 10. Atlanta Gastroenterology Association, Atlanta, GA, United States. 11. Yale School of Medicine, New Haven, CT, United States. 12. Scripps Clinic, La Jolla, CA, United States. 13. Janssen Research & Development, Beerse, Belgium. 14. Novellas Healthcare, Zellik, Belgium. 15. Gilead Sciences Inc, Foster City, CA, United States. 16. Janssen Research & Development LLC, Titusville, NJ, United States. 17. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX, United States.

  41. Background Simeprevir (TMC435) is an investigational, one pill, once-daily, potent oral HCV NS3/4A protease inhibitor recently approved in Japan and currently under regulatory review in North America and Europe Sofosbuvir (GS-7977) is an HCV nucleotide NS5B polymerase inhibitor also currently under regulatory review COSMOS is a Phase IIa, randomized, open-label study investigating simeprevir + sofosbuvir +/- ribavirin Interim analysis Jacobson IM, et al. Abstract #LB-3, AASLD 2013

  42. COSMOS: Study design N=14 0 4 12 24 36 48 N=24 Week N=14 SMV + SOF + RBV Post-treatment follow-up Arm 1 N=27 Enrollment ratio 2:1:2:1 Post-treatment follow-up SMV + SOF Arm 2 Post-treatment follow-up SMV + SOF + RBV Arm 3 Post-treatment follow-up SMV + SOF Arm 4 • Cohort 1: Prior null responders (METAVIR F0-F2) • Final SVR12 for all arms • Cohort 2: Treatment-naïve and prior null responders (METAVIR F3-F4) • Interim SVR4 for Arms 3 and 4 Jacobson IM, et al. Abstract #LB-3, AASLD 2013

  43. Cohort 1: Null responders (F0-2) 24 week treatment 12 week treatment 6.7 1/27 1/14 1/24 1/15 4/24 Patients (%) 13/14 26/27 19/24 14/15 SMV/SOF12 wks SMV/SOF/RBV12 wks SMV/SOF 24 wks SMV/SOF/RBV 24 wks Non-virologic failure SVR12 (SMV/SOF) SVR12 (SMV/SOF/RBV) Relapse Jacobson IM, et al. Abstract #LB-3, AASLD 2013

  44. Cohort 2: Naïve and prior null responders (F3-4): Interim analysis, SVR4 12 week treatment 1/27 1/15 SVR4 (SMV/SOF) SVR4 (SMV/SOF/RBV) Patients (%) Relapse 7/7 12/12 7/7 14/15 26/27 14/14 Jacobson IM, et al. Abstract #LB-3, AASLD 2013

  45. Most Common AEs: Cohorts 1 and 2 Combined aNo sun-protective measures were in place for this trialRBV, ribavirin; SMV, simeprevir; SOF, sofosbuvir Jacobson IM, et al. Abstract #LB-3, AASLD 2013

  46. Conclusion • Treatment with SMV + SOF ± RBV results in: • High SVR12 rates in HCV GT 1 null responder patients • High SVR4 rates in naïve and null-responder patients with METAVIR F3-F4 • Addition of RBV to SMV + SOF may not be needed to achieve high rates of SVR in this patient population • 12 weeks of treatment may confer similar SVR rates compared with 24 weeks of treatment • SMV + SOF ± RBV was generally well tolerated Jacobson IM, et al. Abstract #LB-3, AASLD 2013

  47. Abstract #3 Twice-Daily Telaprevir in Combination with Peginterferon Alfa-2a/Ribavirin in Genotype 1 HCV Liver Transplant Recipients: Interim Week 16 Safety and Efficacy Results of the Prospective, Multicenter REFRESH Study Kimberly Ann Brown1, Robert J. Fontana2, Mark W. Russo3, Josh Levitsky4, Eric M. Yoshida5, Hugo E. Vargas6, Mohammad Bsharat7, Raymond A. Rubin7, Robert S. Brown8 1. Henry Ford Hospital, Detroit, MI, United States. 2. University of Michigan, Ann Arbor, MI, United States. 3. Carolinas Medical Center, Charlotte, NC, United States. 4. Northwestern University, Chicago, IL, United States. 5. University of British Columbia, Chicago, IL, United States. 6. Mayo Clinic, Scottsdale, AZ, United States. 7. Vertex Pharmaceuticals Incorporated, Cambridge, MA, United States. 8. Columbia University, New York, NY, United States.

  48. REFRESH Study Design* SVR 12 Follow-up T/PR PR Week 0 4 12 24 36 48 60 Week 4 safety review before enrolling patients in Part B *The design was the same for both Parts A and B. SVR12, sustained viral virologic response at 12 weeks. Brown KA, et al. Abstract #3, AASLD 2013 • No PR lead-in used • Patients received T/PR (TVR, 1125 mg twice daily; Peg-IFN 180 µg/week; RBV 600 mg/day [initial dosage]) for 12 weeks, plus 36 weeks of PR • Since treatment with T/PR has not been previously studied in liver transplant recipients with HCV infection, this study was designed in two parts. After all patients in Part A reached week 4, a safety review of available safety, PK, and HCV RNA data was conducted before initiating enrollment in Part B • Dose adjustments in Peg-IFN and/or RBV permitted • All study drugs were discontinued if HCV RNA was >1000 IU/mL at weeks 4, 8, or 12, or if it was<25 IU/mL, target detected at weeks 24 or 36

  49. On-Treatment HCV Virologic Response Patients (%) n=6 n=23 n=11 n=0 n=18 n=3 n=3 Week 4 (n=43)* Week 12 (n=30)* *As the study is ongoing, data are reported for patients with HCV RNA assessments available at the time of interim analysis. LLOQ = 25 IU/mL. Brown KA, et al. Abstract #3, AASLD 2013

  50. Adverse Events and Serious Adverse Events *Patients may have reported ≥1 serious AE. †Grouped adverse event terms. Brown KA, et al. Abstract #3, AASLD 2013 Five (13%) patients in the TAC group experienced serious AEs* Two (29%) patients in the CsA group experienced serious AEs* No rejections, autoimmune hepatitis, or deaths have been reported to date

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