Catherine Stedman, MD · afael Esteban1, Lisa Nyberg 2, Jay Lalezari3, Liyun Ni4, Brian Doehle4,...

1

Catherine Stedman, MDChristchurch, New Zealand

This activity is supported by an independent medical education grant from AbbVie, Bristol-Myers Squibb and Gilead Sciences

2

Successful Retreatment of HCV Genotype-1 Infected Patients Who Failed Prior Therapy with Peg-interferon + Ribavirin Plus

1 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

1Universite Paris Decartes, Hopital Cochin, Paris, France; 2John Hopkins University, Baltimore, MD, USA; 3Southern 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

l patients were previously treated with PEG+RBV and an investigational otease inhibitor (GS-9451 or GS-9256) +/- one or two additional DAA

– Tegobuvir (NS5b non-nucleoside polymerase inhibitor)

– Ledipasvir (NS5a inhibitor)

o patients had documented cirrhosis as per the prior protocols

SVR 12SOF + PEG/RBV

Wk 0 Wk 12 Wk 24

12 weeks SOF + PEG/RBV

n=80Mean age, y (range) 55 (21–72)Male, n (%) 60 (75)Black, n (%) 11 (14)Mean BMI, kg/m2 (range) 28 (21–43)IL28B CC, n (%) 13 (16)Mean ALT, U/L (range) 74 (24-298)GT 1a, n (%) 68 (85)Mean baseline HCV RNA, log10 IU/mL (range) 6.6 (5.0–7.3)Mean duration of prior therapy, weeks (range) 25 (1–60)Courses of prior therapy, n (%)

1 44 (55)≥2 36 (45)

Prior DAA Exposure, n (%)1 DAA 15 (19)2 DAA 41 (51)3 DAA 24 (30)

Patients with ≥1 resistance associated variant (RAV), n(%) 72 (90)

Prior response, n (%)Relapse 48 (48)On-treatment failure 36 (45)

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

hree quarters (74%) of DAAs-experienced patients achieved an SVR th 12 weeks of SOF + PEG/RBV therapy despite multiple resistance

ariants and prior courses of therapy

he presence of baseline RAVs against any or all 3 non structural oteins (NS3, NS5a, NS5b) did not impact overall SVR

he 12-week SOF + PEG/RBV regimen was safe and well tolerated

ofosbuvir-containing regimens are effective in these patients with no her currently approved alternatives

ccessful Retreatment With Sofosbuvir-containing Regimens r HCV Genotype 2 or 3 Infected Patients who Failed Prior

Sofosbuvir Plus Ribavirin Therapy

afael 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; Quest Clinical Research, San Francisco, CA, USA; 4Gilead Sciences, Inc., Foster City, CA, USA; dacion de Investigacion, San Juan, Puerto Rico; 6JW Goethe University Hospital, Frankfurt, Germany

pen-label study offered to all GT 2 or 3 treatment failures from FISSION, OSITRON and FUSION

atients offered 2 possible treatment options

– Choice based on patient’s eligibility for IFN and patient/investigator recommendation

cluded patients with compensated cirrhosis

SVR 12

SOF + PEG/RBV SVR 12

SOF + RBV

Wk 0 Wk 12 Wk 24 Wk 36

12 weeks SOF + PEG/RBV

n=34

24 weeks SOF + RBV

n=73Mean age, y (range) 53 (31–70) 53 (38-63)Male, n (%) 26 (77) 63 (86)Black, n (%) 1 (1%) 0Mean BMI, kg/m2 (range) 29 (22–39) 28 (20-41)Cirrhosis* n (%) 14 (41) 25 (34)IL28B CC, n (%) 11 (32) 27 (37)Mean ALT, U/L (range) 96 (14-325) 89 (18-310)Genotype, n (%)

2 6 (18) 5 (7)

3 28 (82) 68 (93)Mean baseline HCV RNA, log10 IU/mL (range) 6.3 (4.8-7.8) 6.6 (4.4–7.6)

*Cirrhosis status determined in parent protocol.

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.

93

74

88

47

0

20

40

60

80

00

12 weeks SOF + PEG/RBV 24 weeks SOF+RBV

No Cirrhosis Cirrhosis

13/14 7/8 17/23 7/15

etreatment with an extended duration of SOF + RBV to 24 weeks or e addition of IFN to a 12 week regimen resulted in high SVR rates in T 2 and GT 3 patients who previously failed SOF+RBV-containing gimens

he 12-week regimen containing IFN had higher overall rates of SVR nd was more effective in patients with cirrhosis

he 24-week IFN-free regimen was safe and well tolerated and offers a treatment option for those ineligible to receive IFN

Simeprevir Plus Sofosbuvir With/Without Ribavirin inHCV Genotype-1 Prior Null-responder /

atment-naïve Patients (COSMOS Study): Primary Endpoint SVR12) Results in Patients With METAVIR F3-4 (Cohort 2)

. 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

xas Liver Institute, San Antonio, 2Medicine and Gastroenterology and Hepatology, The Liver Institute, as, TX, 3Fundacion de Investigacion, San Juan, PR, 4Department of Medicine, Inova Fairfax Hospital, s Church, VA, 5Borland-Groover Clinic, 4800 Belfort Rd, Jacksonville, FL, 6Johns Hopkins University ool of Medicine, Baltimore, MD, 7Orlando Immunology Center, Orlando, FL, 8Atlanta Medical Center, Atlanta, GA, 9University of Pittsburgh Medical Center, Pittsburgh, PA, 10Atlanta Gastroenterology ciation, Atlanta, GA, 11Yale School of Medicine, New Haven, CT, 12Scripps Clinic, La Jolla, CA, United ates, 13Janssen Research & Development, Beerse, 14Novellas Healthcare, Zellik, Belgium, 15Gilead iences 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%

*Excluding patients who discontinued

SMV/SOF±RBVSMV/SOF + RBV SMV/SOF + RBVSMV/SOF SMV/SOF

24 weeks 12 weeks Overall

GT 1b

6/6 11/11 11/11 4/4 7/7 4/4 5/5 13/14 7/8 3/3 7/8 3/3 18/18 38/40 25/26

100

80

40

20

0

60

100 100 100 100 100

notype; non-VF, non-virologic failure; RBV, ribavirinimeprevir; SOF, sofosbuvir; SVR12, sustained virologicse 12 weeks after planned treatment end


GT 1a without Q80K

100 100

9388

95100 100

88

10096



GT 1b

6/6 11/11 11/11 4/4 7/7 4/4 5/5 13/14 7/8 3/3 7/8 3/3 18/18 38/40 25/26

100

80

40

20

0

60

100 100 100 100 100



GT 1a without Q80K

100 100

9388

95

GT 1a with Q80K

100 100

88

10096



GT 1b

6/6 11/11 11/11 4/4 7/7 4/4 5/5 13/14 7/8 3/3 7/8 3/3 18/18 38/40 25/26

100

80

40

20

0

60

100 100 100 100 100




100 100

80

10096

100 100 100

67

94

0

20

40

60

80

100



9/9 3/3 4/4 5/5 4/5 6/6 4/4 2/3 21/22 16/17

Null responders Treatment naïves

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)

enotype; ITT, Intent-to-treat; QD, once daily; RBV, ribavirin; SMV, simeprevir; ofosbuvir; SVR12, sustained virologic response 12 weeks after end of treatment

Oral Fixed-Dose Combination Ledipasvir/Sofosbuvir With Or Without Ribavirin for 12 or 24 Weeks in

Treatment-Naive Genotype 1 HCV-Infected Patients: the Phase 3 ION-1 Study

Alessandra Mangia,1 Patrick Marcellin,2 Paul Kwo,3Graham R. Foster,4 Maria Buti,5 Norbert Bräu,6 Andrew Muir,7

Jenny C. Yang,8 Hongmei Mo,8 Xiao Ding,8 Phil S. Pang,8William T. Symonds,8 John G. McHutchison,8 Stefan Zeuzem,9 Nezam Afdhal10

sa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy; 2Centre Hospitalier Universitaire jon, Clichy-sous-Bois, France; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Queen

s University of London, Barts Health, UK; 5Hospital Universitario Valle de Hebrón, Barcelona, Cataluña, 6Mount Sinai School of Medicine, New York, NY, USA; 7Duke University Medical Center, Durham, NC,

A;6Gilead Sciences, Inc., Foster City, CA; 9Johann Wolfgang Goethe University, Frankfurt, Germany; 10Beth Israel Deaconess Medical Center, Boston, MA, USA

T 1 HCV treatment-naïve patients in Europe and USAoad inclusion criteria

– Targeted 20% enrollment of patients with cirrhosis– No upper age or BMI limit– Platelet count ≥50,000/mm3, no neutrophil minimum

65 patients randomized 1:1:1:1 across four arms ratified by HCV subtype (1a or 1b) and cirrhosis

Wk 0 Wk 12 Wk 36Wk 24

LDV/SOF SVR12

LDV/SOF + RBV

LDV/SOF

LDV/SOF + RBV

SVR12

SVR12

SVR12

ms were balanced with respect to demographics and baseline characteristics

12 Weeks 24 WeeksLDV/SOF

n=214LDV/SOF+RBV

n=217LDV/SOF

n=217LDV/SOF+RBV

n=217n age, y (range) 52 (18–75) 52 (18–78) 53 (22–80) 53 (24–77)

e, n (%) 127 (59) 128 (59) 139 (64) 119 (55)

k, n (%) 24 (11) 26 (12) 32 (15) 26 (12)

anic, n (%) 26 (12) 20 (9) 29 (13) 26 (12)

on Europe 89 (42) 99 (46) 85 (39) 80 (37)

n BMI, kg/m2 (range) 27 (18–41) 27 (18–42) 27 (18–48) 26 (18–48)

hosis 34 (16) 33 (15) 33 (15) 36 (17)

B CC, n (%) 55 (26) 76 (35) 52 (24) 73 (34)

feron ineligible 14 (7) 20 (9) 19 (9) 14 (7)

a, n (%) 144 (67) 148 (68) 146 (67) 143 (66)

n HCV RNA,IU/mL (range) 6.4 (1.6–7.5) 6.4 (4.4–7.6) 6.3 (3.7–7.4) 6.3 (3.2–7.5)

V RNA ≥800,000 IU/mL 169 (79) 173 (80) 168 (77) 173 (80)

99 97 98 99

0

20

40

60

80

100

211/217

12 Weeks 24 Weeks

LDV/SOF + RBV

211/214 212/217

SVR

12 (%

)

215/217

LDV/SOF + RBVLDV/SOF LDV/SOF

r bars represent 95% confidence intervals.

DV/SOF for 12 weeks achieved SVR12 rate of 99% in eatment-naive GT 1 patients – Adding RBV and/or extending LDV/SOF treatment duration to 24 weeks did not

increase SVR12 rates

– Cirrhotic patients achieved SVR12 rates of 94 - 100% with 12-24 weeks of treatment with LDV/SOF with or without RBV

DV/SOF with or without RBV was safe and well tolerated– Addition of RBV contributed to higher incidence of AEs and laboratory

abnormalities

single tablet regimen with the fixed-dose combination LDV/SOF for 2 weeks achieved SVR in most GT 1 previously un-treated patients

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

h Israel Deaconess Medical Center, Boston, MA, USA; 2University of Pennsylvania, Philadelphia, PA, 3Scripps Clinic, La Jolla, CA; 4St Louis University, Saint Louis, MO, USA; 5University of New Mexico,

querque, NM; 6Gilead Sciences, Inc., Foster City, CA; 7Johns Hopkins Medical Center, Baltimore, MD, USA; 8Indiana University School of Medicine, Indianapolis, IN, USA

T 1 HCV patients who had failed prior IFN-based therapy, including regimens containing a NS3/4A otease inhibitor oad inclusion criteria

Targeted 20% enrollment of patients with cirrhosisNo upper age or BMI limitPlatelet count ≥50,000/mm3, no neutrophil minimum

0 patients randomized 1:1:1:1 across four armsatified by HCV subtype (1a or 1b), cirrhosis, prior treatment response

Wk 12 Wk 36Wk 24

DV/SOF SVR12

DV/SOF + RBV

DV/SOF

DV/SOF + RBV

SVR12

SVR12

SVR12

Arms were balanced with respect to demographics and baseline characteristics

12 Weeks 24 Weeks

LDV/SOFn=109

LDV/SOF+RBVn=111

LDV/SOFn=109

LDV/SOF+RBVn=111

Mean age, y (range) 56 (24–67) 57 (27–75) 56 (25–68) 55 (28–70)

Male, n (%) 74 (68) 71 (64) 74 (68) 68 (61)

lack, n (%) 24 (22) 16 (14) 17 (16) 20 (18)

ispanic, n (%) 7 (6) 12 (11) 11 (10) 11 (10)

Mean BMI, kg/m2 (range) 29 (19–47) 28 (19–45) 28 (19–41) 28 (19–50)

L28B CC, n (%) 10 (9) 11 (10) 16 (15) 18 (16)

T 1a, n (%) 86 (79) 88 (79) 85 (78) 88 (79)

Mean HCV RNA,g10 IU/mL (range) 6.5 (5.0–7.5) 6.4 (4.6–7.3) 6.4 (4.7–7.4) 6.5 (3.1–7.4)

CV RNA ≥800,000 IU/mL 103 (95) 98 (88) 93 (85) 96 (87)

rior non-responders, n (%) 49 (45) 46 (41) 49 (45) 51 (46)

rior protease inhibitor ailures, n (%) 66 (61) 64 (58) 50 (46) 51 (46)

irrhosis, n (%) 22 (20) 22 (20) 22 (20) 22 (20)

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

bars represent 95% confidence intervals.

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


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


ngle tablet fixed dose combination of LDV/SOF with or without RBV treatment-experienced GT 1 patients resulted in an SVR of 94 -99%

aseline NS5a or NS3/4 mutations had no effect on SVR

BV did not enhance SVR rates, alter viral kinetics or prevent relapse

he majority of subjects who relapsed had cirrhosis

DV/SOF ± RBV was safe and well tolerated

– Addition of RBV contributed to higher incidence of AEs and laboratory abnormalities

N, et al. NEJM In Press

Ledipasvir/Sofosbuvir With and Without Ribavirin for 8 Weeks Compared to Ledipasvir/Sofosbuvir for 12 Weeks in

Treatment-Naïve Noncirrhotic Genotype-1 HCV-Infected Patients: The Phase 3 ION-3 Study

V. Kowdley1, Stuart C. Gordon 2, K. Rajender Reddy3, Lorenzo Rossaro4, David E. Bernstein5,Di An6, Evguenia S. Svarovskaia6, Robert H. Hyland6, Phillip S. Pang6,

William T. Symonds6, John G. McHutchison6, Andrew J. Muir7, Paul J. Pockros8, David C. Pound9, Michael W. Fried10

Virginia Mason Medical Center, Seattle, WA, USA; 2Henry Ford Health System, Detroit, MI, USA; Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA; 4University of ornia Davis Medical Center, Sacramento, CA, USA; 5North Shore University Hospital, Manhasset, NY, A; 6Gilead Sciences, Inc., Foster City, CA; 7Division of Gastroenterology and Duke Clinical Research te, Duke University School of Medicine, Durham, NC, USA; 8Scripps Clinic, La Jolla, CA; 9Indianapolis oenterology Research Foundation, Indianapolis, IN, USA; 10University of North Carolina at Chapel Hill,

Chapel Hill, NC, USA

T 1 treatment-naïve patients without cirrhosisoad inclusion criteria

– No upper age or BMI limit– Opiate substitution therapy allowed47 patients randomized 1:1:1 across three armsratified by HCV subtype (1a or 1b)

LDV/SOF

LDV/SOF

LDV/SOF + RBV

Wk 8 Wk 12 Wk 24Wk 20

SVR12

SVR12

SVR12

94 93 95

0

20

40

60

80

100

p=0.70 p=0.30

206/216

8 Weeks 12 WeeksLDV/SOFLDV/SOF LDV/SOF + RBV

201/216202/215 206/216

SVR

12 (%

)

p=0.52


ey K, et al. NEJM In Press

DV/SOF ± RBV for 8 or 12 weeks results in highVR12 rateso difference in efficacy among the groups was observedost and viral factors traditionally associated with lower VR rates did not affect SVR12 ratesDV/SOF ± RBV was safe and well tolerated– RBV contributed to a higher incidence of AEs and laboratory

abnormalities

n 8 week LDV/SOF treatment regimen is a safe and ffective treatment for treatment-naïve non-cirrhotic atients with HCV GT 1 infection

Sofosbuvir/Ledipasvir Fixed Dose Combination is Safe and ffective in Difficult-to-treat Populations Including Genotype-3 tients, Decompensated Genotype-1 Patients, and Genotype-1

Patients With Prior Sofosbuvir Treatment Experience

J. Gane1, R.H. Hyland2, D. An2, P.S. Pang2, W.T. Symonds2, J.G. McHutchison2, C.A. Stedman3

kland Clinical Studies, Auckland, New Zealand; 2Gilead Sciences, Inc., Foster City, CA, United States; 3Christchurch Clinical Studies Trust, Christchurch, New Zealand

Wk 0 Wk 12 Wk 24

SVR12

LDV/SOF + RBV, n=26

LDV/SOF, n=25GT 3

Treatment naïve

Ran

dom

ized

HCV GT 1, relapsed after previous treatment with SOF-containing regimens in ELECTRON-1HCV GT 1 decompensated cirrhosis (Child Pugh Turcotte B)HCV GT 3, treatment naïve

LDV/SOF + RBV, n=19GT 1

rior SOF exposure

GT 1CPT class B LDV/SOF, n=20

100

0

20

40

60

80

100

LDV/SOF + RBV

12 Weeks

19/19

SVR

12 (%

)

Re-treatment

9669 + SOFBV 12 wkment Naïve

+RBV 12 wk rior Nullsponders

n=6n=4

n=8

n=1

LDV/SOF +RBV6 wk

Treatment Naïve

SOF+RBV 12 wk Treatment Naïve

19/19

l 19 previous SOF-regimen failures had relapsed

65

0

20

40

60

80

100

LDV/SOF 12 Weeks

SVR

12(%

)

13/20

GT 1CPT 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 INRrange) 1.2 (1.0-3.0)

Ascites, n (%) 4 (20)

Hepatic encephalopathy, n (%) 6 (30)

Median platelet count,103/µL (range) 84 (44-162)

7 relapsers

bar represents the 95% confidence interval.

SVR

12 (%

)

16/25 26/26

100

64*

0

20

40

60

80

100

LDV/SOF + RBV 12 Weeks

26/2616/25

LDV/SOF 12 Weeks

e due to relapse (n=8) or discontinuation due to AE (n=1)

V/SOF regimens for 12 weeks are safe and ective IFN-free treatments for many diverse and ficult-to-treat patient populations including:

atients infected with HCV GT 1 who have failed revious SOF-containing regimens

atients infected with HCV GT 1 with ecompensated cirrhosis

atients infected with HCV GT 3

SAPPHIRE I: Phase 3 Placebo-Controlled Study of nterferon-Free, 12-Week Regimen Of ABT-450/r/ABT-267, BT-333, and Ribavirin in 631 Treatment-Naïve Adults With

Hepatitis C Virus Genotype 1

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

nto Western Hospital Liver Centre, Toronto, ON, Canada; 2Digestive Disease Institute, Virginia Mason al Center, Seattle, WA; 3AbbVie Inc., North Chicago, IL; 4NYU Langone Medical Center, New York, NY; niversity of Florida College of Medicine, Gainesville, FL, United States; 6Gallipoli Medical Research undation; 7The University of Queensland, Brisbane, QLD, Australia; 8Karolinska University Hospital dinge, 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

genotype and subtype were assessed using the Versant HCV Genotype Inno-LiPA Assay, v2.0.

3D + RBV(N=473)

Placebo(N=158)

e, n (%) 271 (57.3) 73 (46.2)e, n (%)hite 428 (90.5) 144 (91.1)ack 26 (5.5) 8 (5.1)

panic/Latino ethnicity, n (%) 27 (5.7) 5 (3.2)dian age, years (range) 52.0 (18.0-70.0) 52.0 (21.0-70.0)dian BMI, kg/m2 (range) 25.2 (18.0-38.4) 25.5 (18.5-39.4)osis stage, n (%)0-F1 363 (76.7) 116 (73.4)2 70 (14.8) 27 (17.1)3 40 (8.5) 15 (9.5)

8B non-CC genotype, n (%) 329 (69.6) 108 (68.4)V subtype, n (%)a 322 (68.1) 105 (66.5)b 151 (31.9) 53 (33.5)dian HCV RNA, log10 IU/mL (range) 6.51 (3.58-7.60) 6.64 (3.71-7.51)

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, 6Hopital 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

3D + RBV(N=297)

Placebo(N=97)

e / female, n (%) 167 (56.2) / 130 (43.8) 60 (61.9) / 37 (38.1)e, n (%) 269 (90.6) 86 (88.7)ian age, years (range) 54.0 (19.0-71.0) 56.0 (30.0-69.0)ian BMI, kg/m2 (range) 26.0 (18.1-38.1) 26.1 (18.5-36.7)osis stage, n (%)0-F1 202 (68.0) 65 (67.0)2 53 (17.8) 17 (17.5)3 42 (14.1) 15 (15.5)B* non-CC genotype, n (%) 263 (88.6) 90 (92.8)

V subtype, n (%)173 (58.2) 57 (58.8)123 (41.4) 40 (41.2)

ian HCV RNA, log10 IU/mL (range) 6.66 (4.61-7.70) 6.55 (5.20-7.55)r pegIFN/RBV response, n (%)elapse 86 (29.0) 29 (29.9)rtial response 65 (21.9) 21 (21.6)ll response 146 (49.2) 47 (48.5)rs12979860

enotype and subtype assessed using the Versant HCV Genotype Inno-LiPA Assay, v2.0.NA level measured by COBAS TaqMan real-time reverse-transcriptase–polymerase-chain-reaction assay, v2.0 (Roche).

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

D: co-formulated ABT-450/r/ombitasvir, 150 mg/100 mg/25 mg QD; asabuvir, 250 mg BID

BV: 1000-1200 mg daily according to body weight (<75 kg and >75kg, spectively)

Day 0 Week 24Week 12

SVR12

SVR12

3D + RBV(N=208)

3D + RBV(N=208)

3D + RBV(N=172)

3D + RBV(N=172)

All patients to be followed through 48 weeks post-treatment

12-Week Arm(N=208)

24-Week Arm(N=172)

e (%) 70.2 70.3ite race (%) 95.7 93.6panic or Latino ethnicity (%) 12.0 11.6an age (years) 57.1 56.5an BMI (kg/m2) 27.9 27.98B non-CC (%) 83.2 80.2V genotype 1a (%) 67.3 70.3atment-naïve (%) 41.3 43.0atment-experienced (%) 58.7 57.0Relapse 13.9 13.4Partial responder 8.7 7.6Null responder 36.1 36.0

telet count <100 x 109/L (%) 21.6 19.2um albumin <3.5 g/dL (%) 12.0 10.5ld-Pugh score >5 (%) 18.3 18.6

3D + RBV

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

0

20

40

60

80

0092.2 92.9

Naïve Prior RelapseResponse

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

irst dedicated trial of IFN-free regimen in cirrhotic patients, cluding patients often ineligible for clinical trials ow platelets, low albumin, radiographic ascites)

VR rates of 92% to 96% with 12 and 24 weeks of eatment, with high SVR rates in all subgroups analyzed

2 or 24 weeks of treatment were similarly well tolerated, ith low rates of treatment discontinuation

fficacy and safety in this large cirrhotic population is similar o non-cirrhotics treated with the same regimen

All-Oral Dual Therapy With Daclatasvirand Asunaprevir in Patients With

HCV Genotype 1b Infection: Phase 3 HALLMARK-DUAL Study Results

Manns1, S. Pol2, I. Jacobson3, P. Marcellin4, S. Gordon5, C.-Y. Peng6, T.-T. Chang7, G. Everson8, J. , 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

tment of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany, 2H_pital Cochin, Paris, ce, 3Weill Cornell Medical College, New York, NY, United States, 4Hopital Beaujon, Clichy, France, 5Henry Ford Health Systems, it, MI, United States, 6School of Medicine, China Medical University, Taichung, 7National Chen Kung University Hospital, Tainan, an, 8University Of Colorado Denver, Aurora, CO, United States, 9Pusan National University Hospital, Busan, Korea, Republic of,

ersity of Duisburg-Essen, Essen, Germany, 11VAMC, Baylor College of Medicine, Houston, TX, 12Kaiser Permanente, Los Angeles, nited States, 13H_pital Saint Joseph, Marseille, 14CHU Purpan, Toulouse, France, 15Taipei Veterans General Hospital and National Ming University, Taipei, Taiwan, 16Monash Health and Monash University, Melbourne, VIC, Australia, 17INSERM Unit_ 954, Centre italier Universitaire de Nancy and Universit_ de Lorraine, Vandoeuvre-l_s-Nancy, 18H_pital Piti_-Salp_tri_re, Paris, France, 19Inje sity Busan Paik Hospital, Busan, Korea, Republic of, 20National Taiwan University Hospital, Taipei, Taiwan, 21Bristol-Myers Squibb esearch and Development, Wallingford, CT, 22Bristol-Myers Squibb Research and Development, Princeton, NJ, United States

imary endpoint: proportion of DCV + ASV-treated patients with SVR12atients infected with HCV genotype 1b

Treatment-naiveNonresponders: prior null or partial response to pegIFN/RBVInterferon-ineligible/intolerant (treatment-naive 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

ble/intolerant

eatment-naive

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

eter

Treatment-naiveDCV + ASV(N = 205)

Treatment-naivePlacebo(N = 102)

Nonrespondera

(N = 205)

Ineligible/intolerantb

(N = 235)edian years 55 54 58 60(%) 101 (49) 54 (53) 111 (54) 98 (42)

n (%)135 (66) 59 (58) 148 (72) 169 (72)

14 (7) 8 (8) 10 (5) 10 (4) 52 (25) 33 (32) 45 (22) 56 (24)

NA, n (%),000 log10 IU/mL 53 (26) 26 (25) 27 (13) 48 (20),000 log10 IU/mL 152 (74) 76 (75) 178 (87) 187 (80)is, n (%) 33 (16) 16 (16) 63 (31) 111 (47)

genotype, n (%)76 (37) N/A 29 (14) 82 (35)

CC 129 (63) N/A 173 (84) 143 (61)s 119 (58%) null responders, 84 (41%) partial responders, and 2 (1%) relapsers.s 71 (30%) patients with depression, 87 (37%) with anemia/neutropenia, and 77 (33%) with compensated advanced irrhosis with thrombocytopenia (6 with advanced fibrosis [F3], 70 with cirrhosis [F4], and 1 not reported).

9082 82

0

20

40

60

80

100

Treatment-naive

Nonresponders Ineligible/intolerant

SVR

12(%

of p

atie

nts)

a,b

• SVR12 rates documented on or after posttreatment Week 12– Treatment-naive: 91%– Nonresponders: 82%– Ineligible/intolerant: 83%

RNA < lower limit of assay quantitation (25 IU/mL)nts with missing SVR12 data counted as treatment failures

182/203 168/205 192/235

90

0

0

0

0

0

082 81 80

91

73

Nonresponder Ineligible/intolerantTreatment-naive

Null Partial Depression Anemia/neutropeniaa

Advancedfibrosis/cirrhosisw/ thrombocytopeniab

mia: screening hemoglobin 8.5 to < 12 (female) or < 13 (male) g/dL and/or history of anemia on pegIFN/RBV; penia: screening absolute neutrophils 0.5 to < 1.5 x 109 cells/L and/or history of neutropenia on pegIFN/RBVening platelets 50 to < 90 x 109 cells/L and/or history of thrombocytopenia on pegIFN/RBV

182/203 98/119 68/84 57/71 79/87 56/77

nts, n (%)

Treatment-naive

(N = 203)Nonresponder

(N = 205)

Ineligible/intolerant

(N = 235)21 (10) 37 (18) 43 (18)

eatment failuresogic breakthrough 9 (4) 26 (13) 20 (9)ty 0 0 1 (0.4)ctable or missing RNA at end of ment 4 (2) 3 (1) 8 (3)

eatment failurespsea 5 (3) 7 (4) 12 (6)ng RNA at posttreatment Week 3 (2) 1 (1) 2 (1)

ntages based on number of patients with undetectable HCV RNA at end of treatment (treatment-naive, n = 189; onder, n = 174; ineligible/intolerant, n = 204).

ll-oral DCV + ASV therapy achieved SVR12 rates up to 1% in treatment-naive, 82% in nonresponder, and 83% in eligible/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

CV + ASV was generally safe and well toleratedOnly 2% of patients discontinued treatment due to adverse events

CV is being further evaluated in all-oral combinations in multiple patient populations of high unmet need

Catherine Stedman, MD · afael Esteban1, Lisa Nyberg 2, Jay Lalezari3, Liyun Ni4, Brian Doehle4,...

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