1
Rafael Esteban, MDBarcelona, Spain
This activity is supported by an independent medical education grant from AbbVie, Bristol-Myers Squibb and Gilead Sciences
2
Simeprevir Plus Sofosbuvir With/Without Ribavirin inHCV Genotype-1 Prior Null-responder /
Treatment-naïve Patients (COSMOS Study): Primary Endpoint (SVR12) Results in Patients With METAVIR F3-4 (Cohort 2)
E. Lawitz1, R. Ghalib2, M. Rodriguez-Torres3, Z.M. Younossi4, A. Corregidor5, M.S. Sulkowski6,E. DeJesus7, B. Pearlman8, M. Rabinovitz9, N. Gitlin10, J.K. Lim11, P.J. Pockros12, B. Fevery13,T. Lambrecht14, S. Ouwerkerk-Mahadevan13, K. Callewaert13, W.T. Symonds15, G. Picchio16,
K. Lindsay16, M. Beumont-Mauviel13, I.M. Jacobson17
1Texas Liver Institute, San Antonio, 2Medicine and Gastroenterology and Hepatology, The Liver Institute, Dallas, TX, 3Fundaci_n de Investigaci_n, San Juan, PR, 4Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, 5Borland-Groover Clinic, 4800 Belfort Rd, Jacksonville, FL, 6Johns Hopkins University School of Medicine, Baltimore, MD, 7Orlando Immunology Center, Orlando, FL, 8Atlanta Medical Center,
Atlanta, GA, 9University of Pittsburgh Medical Center, Pittsburgh, PA, 10Atlanta Gastroenterology Association, Atlanta, GA, 11Yale School of Medicine, New Haven, CT, 12Scripps Clinic, La Jolla, CA, United
States, 13Janssen Research & Development, Beerse, 14Novellas Healthcare, Zellik, Belgium, 15Gilead Sciences Inc, Foster City, CA, 16Janssen Research & Development LLC, Titusville, NJ, 17Weill Cornell
Medical College, New York, NY, United States
ohort 1: METAVIR F0-F2, prior null respondersohort 2: METAVIR F3-F4, prior null responders or treatment-naïve
Stratified by treatment history, HCV GT 1a/1bimary endpoint: SVR12
econdary endpoints: RVR, on-treatment failure, relapse rate, safety and tolerability wice daily; GT, genotype; QD, once daily; RBV, ribavirin; RVR, rapid virologic response;
imeprevir; SOF, sofosbuvir; SVR12, sustained virologic response 12 weeks after end of treatment
0 4 12 24 36 48Week
SMV + SOF + RBV Post-treatment follow-up
SMV + SOF Post-treatment follow-up
Post-treatment follow-up
Post-treatment follow-upSMV + SOF
Arm 1
Arm 2ndomised2:1:2:1
Arm 3
Arm 4
SMV + SOF + RBV
SMV 150 mg QD + SOF 400 mg QD±RBV 1000/1200 mg/day (BID)
F, patients who did not achieve SVR12 for reasons other than virologic failureent-to-treat; Non-VF, Non-virologic failure; RBV, ribavirin; SMV, simeprevir; SOF, sofosbuvir; SVR12, ed virologic response 12 weeks after planned treatment end
wice daily; GT, genotype; QD, once daily; RBV, ribavirin; RVR, rapid virologic response; SMV, simeprevir; ofosbuvir; SVR12, sustained virologic response 12 weeks after end of treatment
7% 7% 7%
0
20
40
60
80
100
SMV/SOF±RBV
Prop
ortio
n of
pat
ient
s (%
)
SMV/SOF + RBV SMV/SOF + RBVSMV/SOF SMV/SOF24 weeks 12 weeks Overall
SVR12 Non-VF Relapse
93% 100% 93%93% 94%
2/30 1/142/27 3/872/87
28/30 16/16 13/1425/27 82/87
3%2%
MV/SOF QD led to SVR12 rates of 93-100% (ITT) HCV GT 1 infected treatment-naïve and prior ull-responder patients with METAVIR F3-4
VR12 rates were high, regardless of baseline haracteristics:– HCV GT 1 subtype, Q80K polymorphism, METAVIR score,
IL28B GT, prior treatment history
MV/SOF QD +/- RBV was safe and well tolerated
wo Phase 3 trials investigating SMV/SOF without BV are ongoing (OPTIMIST-1 and -2)
notype; ITT, Intent-to-treat; QD, once daily; RBV, ribavirin; SMV, simeprevir; ofosbuvir; SVR12, sustained virologic response 12 weeks after end of treatment
ofosbuvir and Ribavirin for the Treatment of Chronic HCV With Cirrhosis and Portal Hypertension With and Without Decompensation: Early Virologic Response and Safety
am Afdhal,1 Gregory Everson,2 Jose Luis Calleja,3 Geoffrey McCaughan,4 William T. Symonds,5
Diana Brainard,5 Jill Denning,5 Theo Brandt-Sarif,5 Lindsay McNair,5 John G. McHutchison,5Arterburn,5 Jaime Bosch,10 Michael Charlton,6 Rajender Reddy,7 Tarik Asselah,8 Edward Gane,9
Xavier Forns10
th Israel Deaconess Medical Center, Boston, MA, USA; 2University of Colorado Denver, Aurora, CO, ; 3Hospital Puerta de Hierro, Madrid, Spain; 4Royal Prince Alfred Hospital, University of Sydney, New outh Wales, Australia; 5Gilead Sciences, Inc., Foster City, CA, USA; 6Mayo Clinic, Rochester, MN, 7University of Pennsylvania, Philadelphia, PA, USA; 8Hopital Beaujon, INSERM U 773 and University
s-Diderot, Clichy, France; 9Auckland City Hospital, Grafton, Auckland, New Zealand; 10Hospital Clinic, t d’Investigacions Biomèdiques August Pi i Sunyer, and Centro de Investigación Biomédica en Red de
Enfermedades Hepáticas y Digestivas, Barcelona, Spain
m: To explore the safety and efficacy of SOF+RBV in HCV-infected patients th portal hypertension ± decompensated liver diseaseimary objective: SVR12
econdary objectives– Effects of 48 weeks of treatment on hepatic portal pressure and function– Safety and clinical improvement as measured by clinical outcomes, CPT, MELD, and
biochemical test results
udy results through the first 24 weeks are presented
SOF 400 mg + RBV 1000-1200 mgSVR 12
SOF 400 mg + RBV 1000-1200 mg
Wk 0 Wk 24 Wk 48 Wk 96Wk 72
HVPG at Day 0 and Week 48
HVPG at Day 0, and Weeks 24 and 72
Arm 1N=25
Arm 2N=25
SVR 12
Observation
ent was a non-responder at Week 8.
56
100 100 100 100
44
75
94* 94 93
0
20
40
60
80
100
2 4 8 12 24Week
CPT A CPT B
5/9 7/16 9/9 12/16 8/8 15/16 8/8 15/16 7/7 14/15
n HCV-infected patients with portal hypertension with nd without hepatic decompensation, treatment with OF+RBV for up to 24 weeks resulted in:
– High rates of virologic suppression irrespective of severity of liver disease
– Decreased necroinflammation with ALT normalization– Improvements in platelet count and albumin– Improvement in ascites and hepatic encephalopathyOF+RBV for up to 24 weeks was generally safe and
well tolerated with low rates of treatment discontinuation ue to AEs– No patients developed worsening or new onset hepatic
decompensation
Sofosbuvir Compassionate Use Program for Patients with evere Recurrent Hepatitis C Including Fibrosing Cholestatic
Hepatitis Following Liver Transplantation
avier Forns1, Martín Prieto2, Michael Charlton3, John G. McHutchison4, William T. Symonds4, a Brainard4, Jill Denning4, Theo Brandt-Sarif4, Paul Chang4, Valerie Kivett4, Robert J. Fontana5,
Thomas F. Baumert6, Audrey Coilly7, Lluís Castells8, François Habersetzer6
Unit, IDIBAPS, CIBEREHD, Hospital Clinic, Barcelona, Spain; 2Hepatology Unit, CIBEREHD, Hospital rsitari i Politècnic La Fe, Valencia, Spain; 3Mayo Clinic, Rochester, MN, USA; 4Gilead Sciences, Foster CA, USA; 5University of Michigan, Ann Arbor, MI, USA; 6Hôpitaux Universitaires de Strasbourg, Inserm110, Strasbourg, France; 7Centre Hépato-Bilaire, Hôpital Paul Brousse, Inserm UMR-S785, Villejuif, e; 8Liver Unit‒Internal Medicine Department, CIBEREHD, Hospital Universitari Vall Hebron, Barcelona
Severe acute hepatitis/early recurrence (<12 months from liver transplant with typical biochemical
and histological findings)n=48
Post transplant compensated and decompensated cirrhosis (liver
biopsy (F4) or clinical decompensation)
n=56
Completed 24-48 weeks treatmentn=72
Early term due to AEn=7
Liver transplantn=12
Deathn=13
SOF Compassionate Use ProgramSOF + RBV ± PEG
n=104
87
62
0
20
40
60
80
100
EOT SVR12
Patients were excluded from this analysis if received a liver transplant (n=8 at EOT; n=12 at SVR12)and/or no data was available (n=3 at EOT; n=7 at SVR12).
81/93 53/85
reatment with SOF + RBV ± PEG in patients with severe ecurrent HCV who have no other treatment options esulted in:
– Higher rates of sustained virologic response than prior standard therapies
– Improved liver function tests in the majority of patients
– Improved clinical outcomes as defined by a decrease in clinical decompensating events
OF + RBV for up to 48 weeks was generally safe and ell tolerated
ccessful Retreatment of HCV Genotype-1 Infected Patients ho Failed Prior Therapy with Peg-interferon + Ribavirin Plus or 2 Other Direct-Acting Antiviral Agents with Sofosbuvir
Stanislas Pol1, Mark Sulkowski2, Tarek Hassanein3, Ed Gane4, Liyun Ni5, Hongmei Mo5, Bittoo Kanwar5, Diana Brainard5, GM Subramanian5, William T. Symonds5,
John G. McHutchison5, Michael Bennett6, Ira M. Jacobson7
versite Paris Decartes, Hopital Cochin, Paris, France; 2John Hopkins University, Baltimore, MD, USA; outhern California Liver Center, Coronado, CA, USA; 4Aukland City Hospital, Auckland, NZ; 5Gilead Sciences, Inc., Foster City, CA, USA; 6Medical Associates Research Group, San Diego, CA, USA;
7Weill Cornell Medical College, New York, NY, USA
15
• All patients were previously treated with PEG+RBV and an investigational protease inhibitor (GS-9451 or GS-9256) +/- one or two additional DAA
– Tegobuvir (NS5b non-nucleoside polymerase inhibitor)
– Ledipasvir (NS5a inhibitor)
• No patients had documented cirrhosis as per the prior protocols
SVR 12SOF + PEG/RBV
Wk 0 Wk 12 Wk 24
Pol, S. et al. EASL 2014, Abstract #O55
16
99 10074
0
20
40
60
80
100
Week 4 End of Treatment SVR12
HC
V R
NA
< LL
OQ
(%)
66/67 67/67 37/50
Pol, S. et al. EASL 2014, Abstract #O55
17
• SVR12 results by prior exposure to different DAA mechanisms of action
50
75
93
0
20
40
60
80
100
6/12 18/24 13/14
SV
R12
(%)
NS3 NS3 + NS5a NS3 + NS5a + NS5b(NNI)
+ PEG/RBV
Pol, S. et al. EASL 2014, Abstract #O55
18
• Three quarters (74%) of DAAs-experienced patients achieved an SVR with 12 weeks of SOF + PEG/RBV therapy despite multiple resistance variants and prior courses of therapy
• The presence of baseline RAVs against any or all 3 non structural proteins (NS3, NS5a, NS5b) did not impact overall SVR
• The 12-week SOF + PEG/RBV regimen was safe and well tolerated
• Sofosbuvir-containing regimens are effective in these patients with no other currently approved alternatives
Pol, S. et al. EASL 2014, Abstract #O55
19
Successful Retreatment With Sofosbuvir-containing Regimens for HCV Genotype 2 or 3 Infected Patients who Failed Prior
Sofosbuvir Plus Ribavirin Therapy
Rafael Esteban1, Lisa Nyberg2, Jay Lalezari3, Liyun Ni4, Brian Doehle4, Bittoo Kanwar4, Diana Brainard4, GM Subramanian4, William T. Symonds4, John G. McHutchison4,
Maribel Rodriquez-Torres5, Stefan Zeuzem6
1Vall d’Hebron Hospital, Barcelona, Spain; 2Kaiser Permanente, San Diego, CA, USA; 3Quest Clinical Research, San Francisco, CA, USA; 4Gilead Sciences, Inc., Foster City, CA, USA;
5Fundacion de Investigacion, San Juan, Puerto Rico; 6JW Goethe University Hospital, Frankfurt, Germany
20
• Open-label study offered to all GT 2 or 3 treatment failures from FISSION, POSITRON and FUSION
• Patients offered 2 possible treatment options
– Choice based on patient’s eligibility for IFN and patient/investigator recommendation
• Included patients with compensated cirrhosis
SVR 12
SOF + PEG/RBV SVR 12
SOF + RBV
Wk 0 Wk 12 Wk 24 Wk 36
Esteban, R. et al. EASL 2014, Abstract #O8
21
100 100 92100 100
63
0
20
40
60
80
100
Week 4 End of Treatment SVR 12
Patie
nts
with
< L
LOQ
(%)
12 weeks SOF+PEG/RBV 24 weeks SOF+RBV
28/28 50/50 24/26 25/4028/28 50/50
• Relapse accounted for all virologic failuresError bars represent 95% confidence intervals.
Esteban, R. et al. EASL 2014, Abstract #O8
22
93
74
88
47
0
20
40
60
80
100
12 weeks SOF + PEG/RBV 24 weeks SOF+RBV
Patie
nts
with
< L
LOQ
(%)
No Cirrhosis Cirrhosis
13/14 7/8 17/23 7/15
Esteban, R. et al. EASL 2014, Abstract #O8
23
• Retreatment with an extended duration of SOF + RBV to 24 weeks or the addition of IFN to a 12 week regimen resulted in high SVR rates in GT 2 and GT 3 patients who previously failed SOF+RBV-containing regimens
• The 12-week regimen containing IFN had higher overall rates of SVR and was more effective in patients with cirrhosis
• The 24-week IFN-free regimen was safe and well tolerated and offers a retreatment option for those ineligible to receive IFN
Esteban, R. et al. EASL 2014, Abstract #O8
24
All Oral Fixed-Dose Combination Ledipasvir/SofosbuvirWith or Without Ribavirin for 12 or 24 Weeks in Treatment-
Experienced Genotype 1 HCV-Infected Patients: The Phase 3 ION-2 Study
Nezam Afdhal1, Rajender K. Reddy2, Paul Pockros3, Adrian M. Di Bisceglie4, Sanjeev Arora5,Jenny C. Yang6, Hadas Dvory-Sobol6, Yanni Zhu6, Phil S. Pang6, William T. Symonds6,
John G. McHutchison6, Mark Sukowski7, Paul Kwo8
1Beth Israel Deaconess Medical Center, Boston, MA, USA; 2University of Pennsylvania, Philadelphia, PA, USA; 3Scripps Clinic, La Jolla, CA; 4St Louis University, Saint Louis, MO, USA; 5University of New Mexico, Albuquerque, NM; 6Gilead Sciences, Inc., Foster City, CA; 7Johns Hopkins Medical Center, Baltimore, MD,
USA; 8Indiana University School of Medicine, Indianapolis, IN, USA
25
• 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/mm3, 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 12 Wk 36Wk 24
LDV/SOF SVR12
LDV/SOF + RBV
LDV/SOF
LDV/SOF + RBV
SVR12
SVR12
SVR12
Afdhal, N. et al. EASL 2014, Abstract #O164
26
94 96 99 99
0
20
40
60
80
100
107/111
12 Weeks 24 Weeks
LDV/SOF + RBV
102/109 108/109
SVR
12 (%
)
110/111
LDV/SOF + RBVLDV/SOF LDV/SOF
Afdhal, N. et al. EASL 2014, Abstract #O164
Error bars represent 95% confidence intervals.
27
93 96 100 9894 97 98 100
0
20
40
60
80
100
Failed PEG/RBV Failed Protease Inhibitor
SVR
12 (%
)
40/43 62/66 45/47 62/64 58/58 49/50 58/59 51/51
12 Weeks 24 WeeksLDV/SOF + RBV LDV/SOF + RBVLDV/SOF LDV/SOF
Afdhal, N. et al. EASL 2014, Abstract #O164
Error bars represent 95% confidence intervals.
28
95 100 99 9986 82100 100
0
20
40
60
80
100
Absence of Cirrhosis Cirrhosis
SVR
12 (%
)
83/87 19/22 89/89 18/22 86/87 22/22 88/89 22/22
12 Weeks 24 Weeks
LDV/SOF + RBV LDV/SOF + RBVLDV/SOF LDV/SOF
Afdhal, N. et al. EASL 2014, Abstract #O164
Error bars represent 95% confidence intervals.
29
• Single tablet fixed dose combination of LDV/SOF with or without RBV in treatment-experienced GT 1 patients resulted in an SVR of 94 -99%
• Baseline NS5a or NS3/4 mutations had no effect on SVR
• RBV did not enhance SVR rates, alter viral kinetics or prevent relapse
• The majority of subjects who relapsed had cirrhosis
• LDV/SOF ± RBV was safe and well tolerated
– Addition of RBV contributed to higher incidence of AEs and laboratory abnormalities
Afdhal N, et al. NEJM In PressAfdhal, N. et al. EASL 2014, Abstract #O164
30
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-Naïve Adults With
Hepatitis C Virus Genotype 1
J.J. Feld1, K.V. Kowdley2, E. Coakley3, S. Sigal4, D. Nelson5, D. Crawford6,7, O. Weiland8, H. Aguilar9,J. Xiong3, B. DaSilva-Tillmann3, L. Larsen3, T. Podsadecki3
1Toronto Western Hospital Liver Centre, Toronto, ON, Canada; 2Digestive Disease Institute, Virginia Mason Medical Center, Seattle, WA; 3AbbVie Inc., North Chicago, IL; 4NYU Langone Medical Center, New York, NY;
5University of Florida College of Medicine, Gainesville, FL, United States; 6Gallipoli Medical Research Foundation; 7The University of Queensland, Brisbane, QLD, Australia; 8Karolinska University Hospital
Huddinge, Karolinska Institutet, Stockholm, Sweden; 9Louisiana Research Center, LLC, Shreveport, LA, United States
D: co-formulated ABT-450/r/ombitasvir, 150 mg/100 mg/25 mg QD; dasabuvir, 250 mg BID
BV: 1000-1200 mg daily according to body weight (<75 kg nd >75kg, respectively)
eek 0 Week 12 Week 24 Week 60 Week 72
3D + RBV(n=473)
Placebo(n=158) 3D + RBV
Double-BlindTreatment Period
Open-LabelTreatment Period
Primary Analysis: SVR12
48-WeekFollow-Up
48-WeekFollow-Up
SVR
12, %
Pat
ient
s
All Patients
96.2% 95.3% 98.0%
455/473 307/322 148/151GT1a GT1b
e ITT SVR12 rate was 96.2% (455/473) for treatment-ïve GT1-infected patients receiving 12 weeks of co-mulated ABT-450/r/ombitasvir + dasabuvir + RBV
R12 rates (ITT) were high regardless of HCV subtype
e rate of virologic failure was low:
– 0.2% breakthrough rate
– 1.5% relapse rate
e regimen was generally well-tolerated, with a low rate study drug discontinuation due to AE(s) (0.6%)
SAPPHIRE II: Phase 3 Placebo-Controlled Study Of nterferon-Free, 12-Week Regimen Of ABT-450/r/ABT-267, T-333, And Ribavirin In Treatment-Experienced Adults With
Hepatitis C Virus Genotype 1 Zeuzem1, I. Jacobson2, T. Baykal3, R.T. Marinho4, F. Poordad5, M. Bourliere6, M. Sulkowski7, H. emeyer8, E. Tam9, P. Desmond10, D. Jensen11, A.M. Di Bisceglie12, P. Varunok13, T. Hassanein14, J.
Xiong3, B. DaSilva-Tillmann3, L. Larsen3, T. Podsadecki3
. Goethe University, Frankfurt, Germany, 2Weill Cornell Medical College, New York, NY, 3AbbVie Inc., h Chicago, IL, United States, 4Centro Hospitalar de Lisboa Norte, Lisbon, Portugal, 5The Texas Liver
ute, University of Texas Health Science Center, San Antonio, TX, United States, 6H_pital Saint Joseph, rseille, France, 7Johns Hopkins University, Baltimore, MD, United States, 8Medizinische Hochschuleover, Hannover, Germany, 9LAIR Centre, Vancouver, BC, Canada, 10St Vincent's Hospital (Melbourne), y, VIC, Australia, 11Center for Liver Diseases, University of Chicago Medical Center Chicago, Chicago, IL, 12Saint Louis University, St. Louis, MO, 13Premier Medical Group of the Hudson Valley, PC,
keepsie, NY, 14Southern California Liver Centers and Southern California Research Center, Coronado, CA, United States
D: co-formulated ABT-450/r/ombitasvir, 150 mg/100 mg/25 mg QD; dasabuvir, 50 mg BIDBV: 1000-1200 mg daily according to body weight (<75 kg and >75kg, spectively)
eek 0 Week 12 Week 24 Week 60 Week 72
3D + RBV(n=297)
Placebo(n=97) 3D + RBV
Double-BlindTreatment Period
Open-LabelTreatment Period
48-WeekFollow-Up
48-WeekFollow-Up
Primary Analysis: SVR12
0
20
40
60
80
100
SVR
12, %
Pat
ient
s
All Patients
96.3% 96.0% 96.7%
286/297 166/173 119/123GT1a GT1b
0
20
40
60
80
100
SVR
12, %
Pat
ient
s
PriorRelapse
95.3% 100% 95.2%
82/86 65/65 139/146Prior
PartialResponse
PriorNull
Response
he ITT SVR12 rate was 96.3% (286/297) for eatment-experienced GT1-infected patients
eceiving 12 weeks of ABT-450/r/ombitasvir + asabuvir + RBV
igh SVR12 rates regardless of HCV subtype and cross all prior pegIFN/RBV response groups
he regimen was generally well-tolerated, with a ow rate of study drug discontinuation due to AE(s) 1.0%)
TURQUOISE-II:SVR12 Rate of 92-96% in 380 Hepatitis C Virus Genotype 1-infected Adults With Compensated
rrhosis Treated With ABT-450/R/ABT-267 and ABT-333 Plus Ribavirin
Poordad1, C. Hezode2, R. Trinh3, K.V. Kowdley4, S. Zeuzem5, K. Agarwal6, M.L. Shiffman7, H. meyer8, T. Berg9, E.M. Yoshida10, X. Forns11, S.S. Lovell3, B. Da Silva-Tillmann3, A.L. Campbell3,
T. Podsadecki3
Texas Liver Institute/University of Texas Health Science Center, San Antonio, TX, United States, 2Henri or Hospital, APHP, University Paris-Est, Inserm U955, Creteil, France, 3AbbVie Inc., North Chicago, IL, gestive Disease Institute, Virginia Mason Medical Center, Seattle, WA, United States, 5J.W. Goethe rsity, Frankfurt, Germany, 6Institute of Liver Studies, Kings College Hospital, London, United Kingdom, Liver Institute of Virginia, Newport News, VA, United States, 8Medizinische Hochschule Hannover, over, 9Universit_tsklinikum Leipzig, Leipzig, Germany, 10University of British Columbia, Vancouver, BC,
Canada, 11Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain
40
• 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 (<75 kg and >75kg, respectively)
Day 0 Week 24Week 12
SVR12
SVR12
3D + RBV(N=208)
3D + RBV(N=208)
3D + RBV(N=172)
3D + RBV(N=172)
Poordad, F. et al. EASL 2014, Abstract #O163
All patients to be followed through 48 weeks post-treatment
41
0
20
40
60
80
100
SVR
12, %
Pat
ient
s
12 Weeks3D + RBV
91.8
191/208
95.9
165/17224 Weeks3D + RBV
P=0.089
Poordad, F. et al. EASL 2014, Abstract #O163
42
0
20
40
60
80
10092.2 92.9
Naïve Prior RelapseResponse
SVR
12, %
Pat
ient
s
59/64 14/1552/56 13/13
93.3 100 100 100 80.0 92.9
11/11 40/5010/10 39/42
Prior PartialResponse
Prior NullResponse
HCV Subtype 1a
12-week arm24-week arm
3D + RBV
Poordad, F. et al. EASL 2014, Abstract #O163
43
• First dedicated trial of IFN-free regimen in cirrhotic patients, including patients often ineligible for clinical trials (low platelets, low albumin, radiographic ascites)
• SVR rates of 92% to 96% with 12 and 24 weeks of treatment, with high SVR rates in all subgroups analyzed
• 12 or 24 weeks of treatment were similarly well tolerated, with low rates of treatment discontinuation
• Efficacy and safety in this large cirrhotic population is similar to non-cirrhotics treated with the same regimen
44
All-Oral Dual Therapy With Daclatasvirand Asunaprevir in Patients With
HCV Genotype 1b Infection: Phase 3 HALLMARK-DUAL Study Results
M. Manns1, S. Pol2, I. Jacobson3, P. Marcellin4, S. Gordon5, C.-Y. Peng6, T.-T. Chang7, G. Everson8, J. Heo9, G. Gerken10, B. Yoffe11, W.J. Towner12, M. Bourliere13, S. Metivier14, C.-J. Chu15, W. Sievert16,
J.-P. Bronowicki17, D. Thabut18, Y.-J. Lee19, J.-H. Kao20, F. McPhee21, J. Kopit21, P. Mendez22, M. Linaberry22, E. Hughes22, S. Noviello22, HALLMARK DUAL Study Team
1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany, 2H_pital Cochin, Paris, France, 3Weill Cornell Medical College, New York, NY, United States, 4Hopital Beaujon, Clichy, France, 5Henry Ford Health Systems, Detroit, MI, United States, 6School of Medicine, China Medical University, Taichung, 7National Chen Kung University Hospital, Tainan, Taiwan, 8University Of Colorado Denver, Aurora, CO, United States, 9Pusan National University Hospital, Busan, Korea, Republic of,
10University of Duisburg-Essen, Essen, Germany, 11VAMC, Baylor College of Medicine, Houston, TX, 12Kaiser Permanente, Los Angeles, CA, United States, 13H_pital Saint Joseph, Marseille, 14CHU Purpan, Toulouse, France, 15Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan, 16Monash Health and Monash University, Melbourne, VIC, Australia, 17INSERM Unit_ 954, Centre
Hospitalier Universitaire de Nancy and Universit_ de Lorraine, Vandoeuvre-l_s-Nancy, 18H_pital Piti_-Salp_tri_re, Paris, France, 19Inje University Busan Paik Hospital, Busan, Korea, Republic of, 20National Taiwan University Hospital, Taipei, Taiwan, 21Bristol-Myers Squibb
Research and Development, Wallingford, CT, 22Bristol-Myers Squibb Research and Development, Princeton, NJ, United States
45
• Primary endpoint: proportion of DCV + ASV-treated patients with SVR12• Patients infected with HCV genotype 1b
– Treatment-naïve– Nonresponders: prior null or partial response to pegIFN/RBV– Interferon-ineligible/intolerant (treatment-naïve or -experienced) due to
• Depression• Anemia/neutropenia• Compensated advanced fibrosis/cirrhosis (F3/F4) with thrombocytopenia
Ran
dom
izat
ion
2:1
STOP
DCV + ASV 24 weeks(N = 205)
DCV + ASV 24 weeks(N = 235)
Week 24 Week 48Day 1 Week 12
Nonresponder
Ineligible/intolerant
Treatment-naïve
DCV 60 mg QD + ASV 100 mg BID 24 weeks(N = 203)a
DCV-PBO + ASV-PBO 12 weeks (N = 102)
Enter another study:DCV + ASV 24 weeks
Follow up 24 weeks
Follow up 24 weeks
Follow up 24 weeks
SVR12
a Excludes 2 patients inadvertently assigned, instead of randomized, to DCV + ASV; patients were excluded from efficacy analyses but both achieved SVR12
Manns, M. et al. EASL 2014, Abstract #O166
46
9082 82
0
20
40
60
80
100
Treatment-naïve
Nonresponders Ineligible/intolerant
SVR
12(%
of p
atie
nts)
a,b
• SVR12 rates documented on or after posttreatment Week 12– Treatment-naïve: 91%– Nonresponders: 82%– Ineligible/intolerant: 83%
a HCV RNA < lower limit of assay quantitation (25 IU/mL)b Patients with missing SVR12 data counted as treatment failuresManns, M. et al. EASL 2014, Abstract #O166
182/203 168/205 192/235
47
• All-oral DCV + ASV therapy achieved SVR12 rates up to 91% in treatment-naïve, 82% in nonresponder, and 83% in ineligible/intolerant patients with genotype 1b
– SVR12 rates were similar in non-cirrhotic (85%) and cirrhotic (84%) patients
– No differences by age, gender, race, IL28B genotype, or prior IFN/RBV treatment experience
• DCV + ASV was generally safe and well tolerated– Only 2% of patients discontinued treatment due to adverse events
• DCV is being further evaluated in all-oral combinations in multiple patient populations of high unmet need
Manns, M. et al. EASL 2014, Abstract #O166