1 Geoffrey Dusheiko, MD London, UK This activity is supported by
an independent medical education grant from AbbVie, Bristol-Myers
Squibb and Gilead Sciences Slide 2 2 All Oral Fixed-Dose
Combination Ledipasvir/Sofosbuvir With or Without Ribavirin for 12
or 24 Weeks in Treatment- Experienced Genotype 1 HCV-Infected
Patients: The Phase 3 ION-2 Study Nezam Afdhal 1, Rajender K. Reddy
2, Paul Pockros 3, Adrian M. Di Bisceglie 4, Sanjeev Arora 5, Jenny
C. Yang 6, Hadas Dvory-Sobol 6, Yanni Zhu 6, Phil S. Pang 6,
William T. Symonds 6, John G. McHutchison 6, Mark Sukowski 7, Paul
Kwo 8 1 Beth Israel Deaconess Medical Center, Boston, MA, USA; 2
University of Pennsylvania, Philadelphia, PA, USA; 3 Scripps
Clinic, La Jolla, CA; 4 St Louis University, Saint Louis, MO, USA;
5 University of New Mexico, Albuquerque, NM; 6 Gilead Sciences,
Inc., Foster City, CA; 7 Johns Hopkins Medical Center, Baltimore,
MD, USA; 8 Indiana University School of Medicine, Indianapolis, IN,
USA Slide 3 3 GT 1 HCV patients who had failed prior IFN-based
therapy, including regimens containing a NS3/4A protease inhibitor
Broad inclusion criteria Targeted 20% enrollment of patients with
cirrhosis No upper age or BMI limit Platelet count 50,000/mm 3, no
neutrophil minimum 440 patients randomized 1:1:1:1 across four arms
Stratified by HCV subtype (1a or 1b), cirrhosis, prior treatment
response Wk 0 Wk 12Wk 36Wk 24 LDV/SOF SVR12 LDV/SOF + RBV LDV/SOF
LDV/SOF + RBV SVR12 Afdhal, N. et al. EASL 2014, Abstract #O109
Slide 4 4 Arms were balanced with respect to demographics and
baseline characteristics Afdhal, N. et al. EASL 2014, Abstract
#O109 12 Weeks24 Weeks LDV/SOF n=109 LDV/SOF+RBV n=111 LDV/SOF
n=109 LDV/SOF+RBV n=111 Mean age, y (range)56 (2467)57 (2775)56
(2568)55 (2870) Male, n (%)74 (68)71 (64)74 (68)68 (61) Black, n
(%)24 (22)16 (14)17 (16)20 (18) Hispanic, n (%)7 (6)12 (11)11 (10)
Mean BMI, kg/m 2 (range)29 (1947)28 (1945)28 (1941)28 (1950) IL28B
CC, n (%)10 (9)11 (10)16 (15)18 (16) GT 1a, n (%)86 (79)88 (79)85
(78)88 (79) Mean HCV RNA, log 10 IU/mL (range) 6.5 (5.07.5)6.4
(4.67.3)6.4 (4.77.4)6.5 (3.17.4) HCV RNA 800,000 IU/mL103 (95)98
(88)93 (85)96 (87) Prior non-responders, n (%)49 (45)46 (41)49
(45)51 (46) Prior protease inhibitor failures, n (%) 66 (61)64
(58)50 (46)51 (46) Cirrhosis, n (%)22 (20) Slide 5 5 Error bars
represent 95% confidence intervals. Afdhal, N. et al. EASL 2014,
Abstract #O109 107/111 12 Weeks24 Weeks LDV/SOF + RBV 102/109
108/109 SVR12 (%) 110/111 LDV/SOF + RBV LDV/SOF Slide 6 6 Error
bars represent 95% confidence intervals. Afdhal, N. et al. EASL
2014, Abstract #O109 Failed PEG/RBVFailed Protease Inhibitor SVR12
(%) 40/43 62/6645/4762/64 58/58 49/50 58/59 51/51 12 Weeks24 Weeks
LDV/SOF + RBV LDV/SOF Slide 7 7 Absence of CirrhosisCirrhosis SVR12
(%) 83/8719/2289/8918/2286/8722/2288/8922/22 12 Weeks24 Weeks
LDV/SOF + RBV LDV/SOF Error bars represent 95% confidence
intervals. Afdhal, N. et al. EASL 2014, Abstract #O109 Slide 8 8
Ledipasvir/Sofosbuvir With and Without Ribavirin for 8 Weeks
Compared to Ledipasvir/Sofosbuvir for 12 Weeks in Treatment-Nave
Noncirrhotic Genotype-1 HCV-Infected Patients: The Phase 3 ION-3
Study Kris V. Kowdley 1, Stuart C. Gordon 2, K. Rajender Reddy 3,
Lorenzo Rossaro 4, David E. Bernstein 5, Di An 6, Evguenia S.
Svarovskaia 6, Robert H. Hyland 6, Phillip S. Pang 6, William T.
Symonds 6, John G. McHutchison 6, Andrew J. Muir 7, Paul J. Pockros
8, David C. Pound 9, Michael W. Fried 10 1 Virginia Mason Medical
Center, Seattle, WA, USA; 2 Henry Ford Health System, Detroit, MI,
USA; 3 Gastroenterology and Hepatology, University of Pennsylvania,
Philadelphia, PA, USA; 4 University of California Davis Medical
Center, Sacramento, CA, USA; 5 North Shore University Hospital,
Manhasset, NY, USA; 6 Gilead Sciences, Inc., Foster City, CA; 7
Division of Gastroenterology and Duke Clinical Research Institute,
Duke University School of Medicine, Durham, NC, USA; 8 Scripps
Clinic, La Jolla, CA; 9 Indianapolis Gastroenterology Research
Foundation, Indianapolis, IN, USA; 10 University of North Carolina
at Chapel Hill, Chapel Hill, NC, USA Slide 9 9 1. Lawitz E, et al.
Lancet. 2014;383:515-23. Kowdley, K. et al. EASL 2014, Abstract
#O56 Short, safe, and effective interferon- and ribavirin-free
treatment options for patients with chronic HCV GT 1 infection are
currently lacking LDV/SOF RBV for 8 weeks and LDV/SOF for 12 weeks
demonstrated high SVR rates in the Phase 2 LONESTAR study in
treatment-nave HCV patients without cirrhosis 1 To evaluate whether
LDV/SOF for 8 weeks is effective for HCV treatment-nave,
non-cirrhotic, GT 1 patients or if RBV or a longer treatment
duration of 12 weeks is required to achieve high SVR rate Slide 10
10 GT 1 treatment-nave patients without cirrhosis Broad inclusion
criteria No upper age or BMI limit Opiate substitution therapy
allowed 647 patients randomized 1:1:1 across three arms Stratified
by HCV subtype (1a or 1b) LDV/SOF LDV/SOF + RBV Wk 0 Wk 8Wk 12Wk
24Wk 20 SVR12 Kowdley, K. et al. EASL 2014, Abstract #O56 Slide 11
11 206/216 8 Weeks12 Weeks LDV/SOF LDV/SOF + RBV
201/216202/215206/216 SVR12 (%) p=0.52 Kowdley, K. et al. EASL
2014, Abstract #O56 Error bars represent 95% confidence intervals.
Slide 12 12 Kowdley K, et al. NEJM In Press Kowdley, K. et al. EASL
2014, Abstract #O56 LDV/SOF RBV for 8 or 12 weeks results in high
SVR12 rates No difference in efficacy among the groups was observed
Host and viral factors traditionally associated with lower SVR
rates did not affect SVR12 rates LDV/SOF RBV was safe and well
tolerated RBV contributed to a higher incidence of AEs and
laboratory abnormalities An 8 week LDV/SOF treatment regimen is a
safe and effective treatment for treatment-nave non-cirrhotic
patients with HCV GT 1 infection Slide 13 13 Sofosbuvir/Ledipasvir
Fixed Dose Combination is Safe and Effective in Difficult-to-treat
Populations Including Genotype-3 Patients, Decompensated Genotype-1
Patients, and Genotype-1 Patients With Prior Sofosbuvir Treatment
Experience E.J. Gane 1, R.H. Hyland 2, D. An 2, P.S. Pang 2, W.T.
Symonds 2, J.G. McHutchison 2, C.A. Stedman 3 1 Auckland Clinical
Studies, Auckland, New Zealand; 2 Gilead Sciences, Inc., Foster
City, CA, United States; 3 Christchurch Clinical Studies Trust,
Christchurch, New Zealand Slide 14 14 Wk 0 Wk 12Wk 24 SVR12 LDV/SOF
+ RBV, n=26 LDV/SOF, n=25 GT 3 Treatment nave Randomized 1. HCV GT
1, relapsed after previous treatment with SOF-containing regimens
in ELECTRON-1 2. HCV GT 1 decompensated cirrhosis (Child Pugh
Turcotte B) 3. HCV GT 3, treatment nave LDV/SOF + RBV, n=19 GT 1
Prior SOF exposure GT 1 CPT class B LDV/SOF, n=20 Gane, E. et al.
EASL 2014, Abstract #O6 Slide 15 15 19/19 SVR12 (%) Re-treatment
GS-9669 + SOF +RBV 12 wk Treatment Nave SOF+RBV 12 wk Prior Null
Responders n=6 n=4 n=8 n=1 LDV/SOF +RBV 6 wk Treatment Nave SOF+RBV
12 wk Treatment Nave 19/19 All 19 previous SOF-regimen failures had
relapsed Gane, E. et al. EASL 2014, Abstract #O6 Slide 16 16 SVR12
(%) 13/20 GT 1 CPT Class B Median total bilirubin, mg/dL (range)
1.5 (0.7-3.7) Median serum albumin, g/dL (range) 3.1 (2.3-3.8)
Median INR (range) 1.2 (1.0-3.0) Ascites, n (%)4 (20) Hepatic
encephalopathy, n (%) 6 (30) Median platelet count, 10 3 /L (range)
84 (44-162) 7 relapsers Gane, E. et al. EASL 2014, Abstract #O6
Error bar represents the 95% confidence interval. Slide 17 17 SVR12
(%) 16/2526/26 100 64* 0 20 40 60 80 100 LDV/SOF + RBV 12 Weeks
26/2616/25 LDV/SOF 12 Weeks *Failure due to relapse (n=8) or
discontinuation due to AE (n=1) Gane, E. et al. EASL 2014, Abstract
#O6 Slide 18 18 Gane, E. et al. EASL 2014, Abstract #O6 LDV/SOF
regimens for 12 weeks are safe and effective IFN-free treatments
for many diverse and difficult-to-treat patient populations
including: Patients infected with HCV GT 1 who have failed previous
SOF-containing regimens Patients infected with HCV GT 1 with
decompensated cirrhosis Patients infected with HCV GT 3 Slide 19 19
Safety and Efficacy of Treatment With the Interferon-free,
Ribavirin-free Combination of Sofosbuvir+GS-5816 For 12 Weeks in
Treatment Nave Patients With Genotype 1-6 HCV Infection G.T.
Everson 1, T.T. Tran 2, W.J. Towner 3, M.N. Davis 4, D. Wyles 5, R.
Nahass 6, J. McNally 7, D.M. Brainard 7, L. Han 7, B. Doehle 7, E.
Mogalian 7, W.T. Symonds 7, J.G. McHutchison 7, T. Morgan 8, R.T.
Chung 9 1 University of Colorado Denver, Aurora, CO, 2 Cedars-Sinai
Medical Center, 3 Kaiser Permanente, Los Angeles, CA, 4 Digestive
CARE, South Florida Center of Gastroenterology, LLC, Wellington,
FL, 5 University of California, San Diego, CA, 6 ID CARE,
Hillsborough, NJ, 7 Gilead Sciences, Inc., Foster City, 8 VA Long
Beach, Long Beach, CA, 9 Massachusetts General Hospital, Boston,
MA, United States Slide 20 20 Everson, G. et al. EASL 2014,
Abstract #O111 GT 1 (N=55) GT 3 (N=54) GT 2-6 (N=45) SOF + GS-5816
25 mg SOF + GS-5816 100 mg SOF + GS-5816 25 mg SOF + GS-5816 100 mg
SOF + GS-5816 25 mg SOF + GS-5816 100 mg Wk 0Wk 12Wk 24 SVR12 Open
label SOF 400 mg + GS-5816 25 mg for 12 weeks or SOF 400 mg +
GS-5816 100 mg for 12 weeks Treatment-nave patients with HCV GT 1-6
without cirrhosis No ribavirin administered Slide 21 21 Everson, G.
et al. EASL 2014, Abstract #O111 GT 1GT 2GT 3
26/2728/2810/1110/1025/27 Slide 22 22 Everson, G. et al. EASL 2014,
Abstract #O111 GT 4GT 5GT 6 7/76/710/104/45/51/1 Slide 23 23 SOF +
GS-5816 for 12 weeks resulted in SVR12 rates >90% in all HCV
genotypes (1-6) Relapse was observed more often in patients treated
with GS-5816 25 mg (N=3) compared to GS-5816 100 mg (N=1) The
presence of pre-treatment NS5A variants was not predictive of
failure to achieve SVR 12 SOF + GS-5816 was well tolerated with no
discontinuations due to AEs The combination of SOF 400 mg and
GS-5816 100 mg is being evaluated in treatment-experienced patients
and patients with cirrhosis Everson, G. et al. EASL 2014, Abstract
#O111 Slide 24 24 SAPPHIRE-I: Phase 3 Placebo-Controlled Study of
Interferon-Free, 12-Week Regimen of ABT-450/r/ABT-267, ABT-333, and
Ribavirin in 631 Treatment-Nave Adults With Hepatitis C Virus
Genotype 1 J.J. Feld 1, K.V. Kowdley 2, E. Coakley 3, S. Sigal 4,
D. Nelson 5, D. Crawford 6,7, O. Weiland 8, H. Aguilar 9, J. Xiong
3, B. DaSilva-Tillmann 3, L. Larsen 3, T. Podsadecki 3 1 Toronto
Western Hospital Liver Centre, Toronto, ON, Canada, 2 Digestive
Disease Institute, Virginia Mason Medical Center, Seattle, WA, 3
AbbVie Inc., North Chicago, IL, 4 NYU Langone Medical Center, New
York, NY, 5 University of Florida College of Medicine, Gainesville,
FL, United States, 6 Gallipoli Medical Research Foundation, 7 The
University of Queensland, Brisbane, QLD, Australia, 8 Karolinska
University Hospital Huddinge, Karolinska Institutet, Stockholm,
Sweden, 9 Louisiana Research Center, LLC, Shreveport, LA, United
States Slide 25 25 3D: co-formulated ABT-450/r/ombitasvir, 150
mg/100 mg/25 mg QD; dasabuvir, 250 mg BID RBV: 1000-1200 mg daily
according to body weight ( 75kg, respectively) Week 0Week 12Week
24Week 60Week 72 3D + RBV (n=473) Placebo (n=158) 3D + RBV
Double-Blind Treatment Period Open-Label Treatment Period Primary
Analysis: SVR12 48-Week Follow-Up 48-Week Follow-Up Feld, J. et al.
EASL 2014, Abstract #O60 Slide 26 26 SVR12, % Patients All Patients
96.2% 95.3% 98.0% 455/473307/322148/151 GT1a GT1b Feld, J. et al.
EASL 2014, Abstract #O60 Slide 27 27 Event, n/N (%) 3D + RBV
(N=473) SVR12455/473 (96.2) Non-SVR1218/473 (3.8) Virologic failure
Breakthrough 1/473 (0.2) Relapse 7/463 (1.5) Prematurely
discontinued study drug* 7/473 (1.5) Lost to follow-up after
completion of treatment 3/473 (0.6) Breakthrough and relapse rates
of 0.2% and 1.5%, respectively *Patients (n=7) who prematurely
discontinued without breakthrough; 2 due to adverse events, 5
withdrew consent/ lost to follow-up. Feld, J. et al. EASL 2014,
Abstract #O60 Slide 28 28 TURQUOISE-II: SVR12 Rates of 92%-96% in
380 Hepatitis C Virus Genotype 1-Infected Adults With Compensated
Cirrhosis Treated With ABT-450/r/ABT-267 and ABT-333 Plus Ribavirin
(3D+RBV) F. Poordad 1, C. Hezode 2, R. Trinh 3, K.V. Kowdley 4, S.
Zeuzem 5, K. Agarwal 6, M.L. Shiffman 7, H. Wedemeyer 8, T. Berg 9,
E.M. Yoshida 10, X. Forns 11, S.S. Lovell 3, B. Da Silva-Tillmann
3, A.L. Campbell 3, T. Podsadecki 3 1 The Texas Liver
Institute/University of Texas Health Science Center, San Antonio,
TX, United States, 2 Henri Mondor Hospital, APHP, University
Paris-Est, Inserm U955, Creteil, France, 3 AbbVie Inc., North
Chicago, IL, 4 Digestive Disease Institute, Virginia Mason Medical
Center, Seattle, WA, United States, 5 J.W. Goethe University,
Frankfurt, Germany, 6 Institute of Liver Studies, Kings College
Hospital, London, United Kingdom, 7 Liver Institute of Virginia,
Newport News, VA, United States, 8 Medizinische Hochschule
Hannover, Hannover, 9 Universit_tsklinikum Leipzig, Leipzig,
Germany, 10 University of British Columbia, Vancouver, BC, Canada,
11 Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona,
Spain Slide 29 29 3D: co-formulated ABT-450/r/ombitasvir, 150
mg/100 mg/25 mg QD; dasabuvir, 250 mg BID RBV: 1000-1200 mg daily
according to body weight ( 75kg, respectively) Day 0Week 24Week 12
SVR12 3D + RBV N=208 (N=208) 3D + RBV (N=172) All patients to be
followed through 48 weeks post-treatment Poordad, F. et al. EASL
2014, Abstract #O163 Slide 30 30 Poordad, F. et al. EASL 2014,
Abstract #O163 SVR12, % Patients 12 Weeks 3D + RBV 91.8 191/208
95.9 165/172 24 Weeks 3D + RBV P=0.089 Slide 31 31 92.2 12-week arm
24-week arm 92.9 NavePrior Relapse Response 3D + RBV SVR12, %
Patients 59/64 14/15 52/56 13/13 93.3100 80.092.9 11/11 40/50 10/10
39/42 Prior Partial Response Prior Null Response HCV Subtype 1a
Poordad, F. et al. EASL 2014, Abstract #O163 Slide 32 32 Results Of
The Phase 2 Study M12-999: Interferon-Free Regimen Of
ABT-450/r/ABT-267+ABT- 333+Ribavirin In Liver Transplant Recipients
With Recurrent HCV Genotype 1 Infection P. Kwo 1, P. Mantry 2, E.
Coakley 3, H. Te 4, H. Vargas 5, R. Brown Jr. 6, F. Gordon 7, J.
Levitsky 8, N. Terrault 9, J. Burton Jr 10, W. Xie 3, C. Setze 3,
P. Badri 3, R.A. Vilchez 3, X. Forns 11 1 Indiana University,
Indianapolis, IN, 2 The Liver Institute at Methodist Dallas Medical
Center, Dallas, TX, 3 AbbVie Inc., North Chicago, 4 University of
Chicago Medicine, Chicago, IL, 5 Mayo Clinic, Phoenix, AZ, 6
Columbia University Medical Center Center for Liver Disease and
Transplantation, New York, NY, 7 Lahey Hospital & Medical
Center, Burlington, MA, 8 Northwestern University Comprehensive
Transplant Center, Chicago, IL, 9 University of California, San
Francisco, San Francisco, CA, 10 University of Colorado, Denver,
Aurora, CO, United States, 11 Liver Unit, Hospital Clinic, IDIBAPS
and CIBEREHD, Barcelona, Spain Slide 33 33 3D: co-formulated
ABT-450/r/ombitasvir, 150 mg/100 mg/25 mg QD; dasabuvir, 250 mg BID
RBV: dosing was managed at the discretion of the investigator and
closely monitored per protocol Day 0Week 24 SVR12 To Week 72 3D +
RBV (N=34) Kwo, P. et al. EASL 2014, Abstract #O114 Slide 34 34
Kwo, P. et al. EASL 2014, Abstract #O114 Based on previous
drug-drug interaction findings, recommended dosing during 3D
treatment was: TAC 0.5 mg once weekly or 0.2 mg every 3 days CYA
1/5 of the daily pre-3D treatment dose given once daily Slide 35 35
No patient had breakthrough One patient had a relapse
(post-treatment day 3) At the time of relapse, this patient had
R155K in NS3 protease, M28T+Q30R in NS5A, and G554S+G557R in NS5B,
none of which were present at baseline Kwo, P. et al. EASL 2014,
Abstract #O114 % Patients 100% 34/34 97.0% 34/34 100% 96.2% 32/33
25/26 SVR4 SVR12 RVR (Week 4) EOTR (Week 24) Slide 36 36 An
IFN-free, 24-week regimen of ABT-450/r/ombitasvir + dasabuvir + RBV
achieved high response rates in immunosuppressed liver transplant
recipients with recurrent HCV GT1 infection In this on-going study:
100% achieved RVR (34/34) and EOTR (34/34) 97.0% (32/33) achieved
SVR4 and 96.2% (25/26) achieved SVR12 The regimen was generally
well tolerated with 1 patient discontinuing study drug due to AEs
No deaths, graft losses, or episodes of rejection CNI dosing was
manageable over the period of the study Kwo, P. et al. EASL 2014,
Abstract #O114 Slide 37 37 Results From the Phase 2 PEARL-I Study:
Interferon-Free Regimens of ABT-450/R + ABT-267 With or Without
Ribavirin in Patients With HCV Genotype 4 Infection C. Hezode 1, P.
Marcellin 2, S. Pol 3, T. Hassanein 4, K. Fleischer-Stepniewska 5,
T. Baykal 6, T. Wang 6, S.S. Lovell 6, T. Pilot-Matias 6, R.A.
Vilchez 6 1 Assistance Publique Hopitaux de Paris, Paris, 2 Hopital
Beaujon Inserm Crb3 - U 773 - Service Hepatologie, Clichy, 3 Groupe
Hospitalier Cochin-Saint Vincent de Paul, Paris, France, 4 Southern
California Liver Centers and Southern California Research Center,
Coronado, CA, United States, 5 EMC Instytut Medyczny Spolka
Akcyjna, Wroclaw, Poland, 6 AbbVie Inc., North Chicago, IL, United
States Slide 38 38 Substudy 1* No Cirrhosis Substudy 2* Compensated
Cirrhosis *Planned number of patients: 40 per treatment arm
ABT-450/r (150/100 mg qd); ombitasvir (25 mg QD); RBV (weight-based
1000 or 1200 mg/day divided BID) All patients followed through 48
weeks post-treatment Group 1 (GT4) (n=44) Group 2 (GT1b) (n=42)
Group 3 (GT1b) (n=40) Group 4 (GT4) (n=42) Group 5 (GT4) Group 6
(GT4) (n=49) BaselineWeek 12 Week 24 ABT-450/r + Ombitasvir
Treatment-Nave Null Responders ABT-450/r + Ombitasvir + RBV
Treatment-Nave ABT-450/r + Ombitasvir Partial/Null Responders &
Relapsers ABT-450/r + Ombitasvir + RBV Partial/Null Responders
& Relapsers Group 7 (GT1b) (n=47) Group 8 (GT1b) (n=52)
ABT-450/r + Ombitasvir Treatment-Nave ABT-450/r + Ombitasvir
Partial/Null Responders & Relapsers ABT-450/r + Ombitasvir
Treatment-Nave Hezode, C. et al. EASL 2014, Abstract #O58 Slide 39
39 97.7% Patients (%) ABT-450/r + Ombitasvir (N=44) ABT-450/r +
Ombitasvir + RBV (N=42) SVR4 SVR12 RVR (Week 4) EOTR (Week 12)
95.5% 93.2% 90.9% 97.6% 100% 43 44 42 44 41 44 40 44 41 42 Hezode,
C. et al. EASL 2014, Abstract #O58 Slide 40 40 Patients (%)
ABT-450/r + Ombitasvir + RBV (N=49) 100% 49/49 37/37 SVR4 RVR (Week
4) EOTR (Week 12) Hezode, C. et al. EASL 2014, Abstract #O58 Slide
41 41 All-oral, IFN-free, 12-week regimens of ABT-450/r +
ombitasvir resulted in: High SVR12 rates in treatment-nave HCV GT4-
infected patients 90.9% with ABT-450/r + ombitasvir 100% with
ABT-450/r + ombitasvir + RBV An SVR4 rate of 100% in
treatment-experienced patients receiving ABT-450/r + ombitasvir +
RBV 12-week regimens of ABT-450/r + ombitasvir +/- RBV were
generally well-tolerated, with no study drug discontinuations or
interruptions due to AEs, and few decreases in hemoglobinSlide 42
42 Safety and Efficacy of the All-oral Regimen of MK- 5172/MK-8742
+ Ribavirin in Treatment-nave, Non- cirrhotic Patients With
Hepatitis C Virus Genotype 1 Infection: The C-WORTHy Study C.
Hezode 1, L. Serfaty 2, J.M. Vierling 3, M. Kugelmas 4, B. Pearlman
5, W. Sievert 6, W. Ghesquiere 7, E. Zuckerman 8, F. Sund 9, M.
Shaughnessy 10, P. Hwang 10, J. Wahl 10, M.N. Robertson 10, B.
Haber 10 1 Department of Hepatology-Gastroenterology, Henri Mondor
Hospital, University of Paris-Est, Creteil, 2 Gastroenterology and
Hepatology, H_pital Saint Antoine, APHP and INSERM UMR_938,
Universit_ Pierre & Marie Curie, Paris, France, 3 Hepatology,
Baylor College of Medicine, Houston, TX, 4 South Denver
Gastroenterology, PC, Englewood, CO, 5 Center for Hepatitis C,
Atlanta Medical Center, Atlanta, GA, United States, 6
Gastrointestinal and Liver Unit, Monash University, Clayton, VIC,
Australia, 7 Vancouver Island Health Authority, Victoria, BC,
Canada, 8 Carmel Medical Center, Technion Faculty of Medicine,
Haifa, Israel, 9 Infectious Diseases, Uppsala University Hospital,
Uppsala, Sweden, 10 Merck, Whitehouse Station, NJ, United States
Slide 43 43 Hezode, C. et al. EASL 2014, Abstract #O10 To assess
the efficacy/safety of an 8- to 12-week regimen of MK-5172 +
MK-8742 weight-based ribavirin in treatment-nave, noncirrhotic
patients with HCV G1 infection Key inclusion/exclusion criteria:
Treatment-nave patients 18 years old with chronic HCV G1a or G1b
infection Liver biopsy or noninvasive test (METAVIR F0-F3) Minimum
baseline hemoglobin: 12 g/dL (females) or 13 g/dL (males) HIV and
hepatitis B virus negative Alanine aminotransferase (ALT) as
aspartate aminotransferase (AST)Slide 44 44 SVR, sustained
virologic response; TW = treatment week. Hezode, C. et al. EASL
2014, Abstract #O110 RBV-Containing RegimenRBV-Free Regimen MK-5172
(100 mg) MK-8742 (20 mg) + RBV MK-5172 (100 mg) MK-8742 (50 mg) +
RBV MK-5172 (100 mg) MK-8742 (50 mg) + RBV MK-5172 (100 mg) MK-8742
(50 mg) MK-5172 (100 mg) MK-8742 (50 mg) MK-5172 (100 mg) MK-8742
(50 mg) + RBV PART A SVR24 (AASLD 2013) PART B Follow-up ongoing
SVR4/8 at SVR4 (28/30 SVR8) 100% at SVR8 Study Week Part A Part B
G1a/b N=25 G1a/b n=27 G1b n=13 G1a n=30 G1a/b n=33 G1a n=31
D1TW4TW8TW12SVR4SVR8SVR12SVR24 Slide 45 45 *Part A: 100% of
patients have completed SVR24; Part B: 8-week arm, 93% of patients
have completed SVR8; 12-week arms, 100% of patients have completed
SVR8; 2 patients (Part A), 2 patients (Part B) discontinued early
(and are counted as failures). Hezode, C. et al. EASL 2014,
Abstract #O110 4-24 30/3081/8544/4430/3082/8544/4425/3080/8543/44
Slide 46 46 Efficacy MK-5172/MK8742 once daily with or without RBV
for 12 weeks is highly efficacious with a SVR of 94%-98%
MK-5172/MK-8742 + RBV for 8 weeks in patients with HCV G1a
infection had an SVR4 4/8 of 83% Most common type of virologic
failure was relapse after a treatment duration of 8 weeks Safety
All treatment regimens were generally safe and well-tolerated There
were no early discontinuations due to drug-related Aes No grade 3
or 4 laboratory abnormalities Hezode, C. et al. EASL 2014, Abstract
#O110 Slide 47 47 Efficacy and Safety of the All-Oral Regimen,
MK-5172/MK- 8742 +/- RBV For 12 Weeks in GT1 HCV/HIV Co-Infected
Patients: The C-WORTHY Study Mark Sulkowski 1, Josep Mallolas 2,
Marc Bourliere 3, Jan Gerstoft 4, Oren Shibolet 5, Ronald Nahass 6,
Edwin DeJesus 7, Melissa Shaughnessy 8, Peggy Hwang 8, Barbara
Haber 8 1 Johns Hopkins University School of Medicine, Baltimore,
MD, USA; 2 Hospital de Dia. Enfermedades Infecciosas, Barcelona,
Spain; 3 Service d'hpato-gastroentrologie, Hpital Saint-Joseph,
Marseille, France; 4 Department of Infectious Diseases,
Rigshospitalet, Copenhagen, Denmark; 5 Liver Unit, Department of
Gastroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; 6 ID
Care, Hillsborough, NJ, USA; 7 Orlando Immunology Center, Orlando,
Florida; 8 Merck & Co., Inc., Whitehouse Station, NJ, USA.
Slide 48 48 Globally, ~7 million patients are co-infected with HIV
and HCV (1) HIV/HCV co-infected patients have a higher rate of
progression to cirrhosis and hepatic decompensation than HCV
mono-infected patients (1-4) MK-5172 and MK-8742 can be dosed with
raltegravir + dual NRTI (tenofovir or abacavir + emtricitabine or
lamivudine) without dosage adjustments MK-5172/MK-8742 has the
potential to provide an all-oral, highly efficacious, simple, and
well-tolerated regimen C-WORTHy: MK-5172/MK-8742 RBV in 471 HCV
G1-infected patients Treatment-naive, non-cirrhotic 12 weeks RBV (n
= 65) Treatment-naive, non-cirrhotic 12 weeks RBV (n = 65)
Treatment-naive Non-cirrhotic 8-12 weeks RBV (n = 94)
Treatment-naive Non-cirrhotic 8-12 weeks RBV (n = 94)
Treatment-naive Cirrhotic 12-18 weeks RBV (n = 123) Treatment-naive
Cirrhotic 12-18 weeks RBV (n = 123) HIV/HCV co-infected
Non-cirrhotic 12 weeks RBV (n = 59) HIV/HCV co-infected
Non-cirrhotic 12 weeks RBV (n = 59) Null responders Cirrhotic /
Non-cirrhotic 12-18 weeks RBV (n = 130) Null responders Cirrhotic /
Non-cirrhotic 12-18 weeks RBV (n = 130) 1. Sulkowski, et al., Clin
Infect Dis. 30 (Suppl 1):S77, 2000; 2. Rockstroh JK, et al., Am J
Gastroenterol. 91:2563, 1996; 3. DHHS Antiretroviral Guidelines;
for Adults and Adolescents. February, 2013; 4. Naggie S, et al.
Gastroenterology. 142:1324, 2012 Sulkowski, M. et al. EASL 2014,
Abstract #O63 Slide 49 49 MK-5172 + MK-8742 + RBV MK-5172 + MK-8742
(No RBV) N = 29 N = 30 Follow-up D1TW12SVR12TW4TW2TW8SVR24SVR4
Primary endpoint MK-5172 (100 mg QD) + MK-8742 (50 mg QD); 12 weeks
Sulkowski, M. et al. EASL 2014, Abstract #O63 Slide 50 50 29 28 29
30 26 29* 27 30 27 30 Virologic Failures: 1 relapse in +RBV arm; 2
breakthrough and 1 lost to follow up in No RBV arm * One patient
has not yet reached FU4 Sulkowski, M. et al. EASL 2014, Abstract
#O63 Slide 51 51 Efficacy Treatment with MK-5172 + MK-8742 RBV for
12 weeks demonstrated high efficacy (90-97% 4 weeks after
end-of-treatment; SVR4) Three of 59 patients experienced virologic
failure 1 relapse, 2 breakthrough Safety MK-5172 + MK-8742 RBV was
generally safe and well tolerated in co- infected patients The most
common AEs in co-infected patients were headache and asthenia All
co-infected patients had suppressed HIV and stable CD4 counts There
were no early discontinuations due to drug-related adverse events
Overall Observed efficacy and safety in patients with HIV/HCV
coinfection was similar to other patient populations in C-WORTHy
Sulkowski, M. et al. EASL 2014, Abstract #O63
