1

Mark Sulkowski, MD Johns Hopkins Medical Center

Baltimore, MD

United States

2

Effectiveness of Hepatitis C Virus (HCV) Testing

for Persons Born During 1945-1965 – Summary

Results from Three Randomized Controlled Trials

Bryce D. Smith1; Anthony K. Yartel2; Kimberly Ann Brown3; Katherine Krauskopf4; Omar I. Massoud5;

Cynthia E. Jordan5; Natalie Kil4; Alex D. Federman4; David R. Nerenz3; Danielle Liffmann6;

David B. Rein6

1. Centers for Disease Control and Prevention, Atlanta, GA

2. CDC Foundation, Atlanta, GA

3. Henry Ford Hospital, Detroit, MI

4. Icahn School of Medicine at Mount Sinai, New York, NY

5. University of Alabama at Birmingham, Birmingham, AL

6. NORC at the University of Chicago, Atlanta, GA

Abstract #194

3

CDC and US Preventive

Services Taskforce

recommend:

One-time testing for HCV

without prior ascertainment

of HCV risk

4

• From December 2012 to February 2014, we conducted HCV (BC)

testing trials at 3 large primary care healthcare centers using

variations of the randomized controlled trial design.

• Across centers, patients born during 1945-1965 with no clinical

documentation of prior HCV test or infection were randomly

assigned (individually or in defined clusters) to receive a 1-time HCV

test (intervention) or the prevailing screening protocol (control).

• We estimated the risk ratio (RR) of identifying patients with HCV

antibody or RNA positive results (HCV+) using BC testing versus

control for each trial, with adjustment for correlated data.

• We applied meta-analysis to summarize individual risk ratios into a

pooled effect estimate.

5

Meta-analysis of Risk Ratios Across Two Sites:

Birth Cohort vs. Usual Care

N=17,464 Log (Risk Ratio) Log (SE) Risk Ratio (95%CI)

Trial #1 2.08 0.79 8.0 (1.7-37.7)

Trial #2 1.17 0.45 3.2 (1.3–7.8)

Pooled Estimate --- --- 4.0 (1.9-8.7)

• Probability of identifying HCV+ patients was 4

times higher using birth cohort testing versus

usual care

6

The Use of All Oral Regimens for Treatment of

Chronic Hepatitis C (CHC) Coupled with Birth

Cohort Screening Is Highly Cost Effective:

The Health and Economic Impact on the

U.S. Population

Zobair Younossi1,3; Mendel Singer2; Linda Henry3; Sharon L. Hunt1,3; Thomas Jeffers1,3;

Spencer Frost1,3; Brian P. Lam1

1. Center for Liver Disease, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA

2. Health Services Research and Policy, Case Western University, Cleveland, OH

3. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA

Abstract #116

7

• As new treatments for HCV are being developed, it

is important that these regimens are assessed

beyond the cost of a pill and assessed for their

“cost per cure” and incremental cost effectiveness

ratio (ICER)

• The economic impact of an effective screening

strategy followed by highly effective treatment of

HCV(+) patients with all oral anti-HCV regimens

have not been fully evaluated

8

• The cost and health benefits of a hepatitis C

screening/treatment program were examined by

computer simulation

• The birth cohort (1945-1965) was modeled over

time using a Markov decision analytic model

• Health outcomes and costs were compared

between Birth Cohort Screening and Risk-Based

Screening

9

• Birth cohort screening followed by treating all

HCV positive patients with all oral anti-HCV

regimens save more than 4 million life years at

an incremental cost of ~$37,000 per QALY

• This strategy is the most cost-effective strategy

from the societal perspective (ICER<$50,000

per QALY)

• Even when considering a very pessimistic

scenario, birth cohort screening-treat all

strategy remains the most cost-effective

strategy

10

Safety and Efficacy of Sofosbuvir-Containing

Regimens for Hepatitis C: Real-World Experience

in a Diverse, Longitudinal Observational Cohort

Donald M. Jensen1; Jacqueline G. O’Leary2; Paul J. Pockros3; Kenneth E. Sherman4; Paul Y. Kwo5;

Mark E. Mailliard6; Kris V. Kowdley7; Andrew J. Muir8; Rolland C. Dickson9; Ananthakrishnan Ramani10,

Michael P. Manns11; Anna S. Lok12; Lucy Akuskevich13; David R. Nelson14; Michael W. Fried13

1. Center for Liver Disease, Univ of Chicago Medical Center,

Chicago, IL

2. Baylor University Medical Center, Dallas, TX

3. Scripps Clinic, LaJolla, CA

4. University of Cincinnati, Cincinnati, OH

5. Indiana University, Indianapolis, IN

6. University of Nebraska Medical Center, Omaha, NE

7. Virginia Mason Medical Center, Seattle, WA

8. Duke University, Durham, NC

9. Dartmouth Hitchcock Medical Center, Lebanon, NH

10. Mountainview Medical Center, Hudson, NY

11. Hannover Medical School, Hannover, Germany

12. University of Michigan Health System, Ann Arbor, MI

13. University of North Carolina, Chapel Hill, NC

14. University of Florida, Gainesville, FL

Abstract #45

11

N=1994

SOF SMV

53.1%

Genotype 1

SOF/SMV/RBV

14.9%

SOF/PEG/R

BV 23.1%

SOF/RBV

8.8%

Genotype 3

SOF/PEG/RBV

8.5%

SOF/RBV

91.5%

Genotype 2

SOF/PEG/RBV

0.9%

SOF/RBV

99.1%

12

SOF PEG

RBV SOF

RBV SOF SMV

SOF SMV

RBV Total*

n(%) N=384 N=667 N=784 N=228 N=2063

MALE 253(66.2) 422 (63.6) 478 (62.0) 147 (65.3) 1300 (63.7)

MEAN Age, y (range) 53.9 (23 - 79) 56.9 (21 - 82) 59.5 (20 - 83) 58.8 (29 - 80) 57.6 (20 - 83)

Age 65+ 31 (8.1) 131 (19.7) 190 (24.6) 40 (17.8) 392 (19.2)

CAUCASIAN 270 (70.3) 539 (80.8) 584 (74.5) 177 (77.6) 1570 (76.1)

BLACK 68 (17.8) 37 (5.6) 96 (12.5) 33 (14.7) 234 (11.5)

TREATMENT STATUS

NAIVE 211 (54.9) 371 (55.6) 318 (40.6) 82 (36.0) 982 (47.6)

EXPERIENCED 172 (44.8) 296 (44.4) 465 (59.3) 144 (63.2) 1077 (52.2)

PI FAILURE 47 (27.3) 25 (8.4) 76 (24.8) 45 (31.3) 193 (17.9)

CIRRHOSIS 120 (31.3) 302 (45.3) 440 (56.1) 137 (60.1) 999 (48.4)

Hx Decompensation 12 (11.4) 136 (49.5) 167 (44.8) 60 (50.8) 375 (43.1)

MELD >10 18 (17.1) 120 (43.6) 122 (32.7) 34 (28.8) 294 (33.8)

LIVER CANCER 25 (6.5) 66 (9.9) 88 (11.2) 32 (14.0) 211 (10.2)

LIVER TRANSPLANT 27 (7.0) 57 (8.5) 111 (14.2) 32 (14.0) 227 (11.0)

HIV 14 (3.6) 18 (2.7) 8 (1.0) 7 (3.1) 47 (2.3)

13

SOF + PEG + RBV

N=209

Latest Available HCV RNA BLOQ

88% (177/200) Latest Available HCV RNA Quantified

12% (23/200)

VBT

0%

(0/164)

Relapse

13%

(21/164)

SVR4 evaluable

164/200

SVR4+ 85% 140/164

Non-Response

1.2%

(2/164)

SVR4+

No cirrhosis: 90% (114/127)

Cirrhosis: 70% (26/37)

Lost to f/u

0.6%

(1/164)

14

Latest Available HCV RNA BLOQ

91% (335/369) Latest Available HCV RNA Quantified

9% (34/369)

VBT

0.33%

(1/303)

Relapse

8.9%

(27/303)

SVR4+

evaluable

303/369

SVR4+ 89% 269/303

Non-Response

2%

(6/303)

SVR4+

No cirrhosis: 92% (113/123)

Cirrhosis: 87% (156/180)

Prior decomp: 75% (61/81)

SVR4+

G1a: 89% (47/53)

G1b: 95% (88/93)

Lost to f/u

0%

(0/303)

SOF + PEG + RBV

N=378

15

86 85 89

84

92 89

85 87 83

90

82

93 87 86

0

20

40

60

80

100

Overall Cirrhotic Non-cirrhotic Genotype 1a Genotype 1b Naïve Experienced

without RBV with RBV

16

• ABT-450 - a potent NS3/4A protease inhibitor.

– Co-dosing of ABT-450 with ritonavir (r; ABT-450/r)

increases the peak, trough, and overall drug

exposures of ABT-450

• Ombitasvir - a potent NS5A inhibitor

• Dasabuvir - a non-nucleoside NS5B

polymerase inhibitor

17

Integrated Efficacy Analysis of Four Phase 3

Studies in HCV Genotype 1a-Infected Patients

Treated with ABT- 450/r/Ombitasvir and Dasabuvir

With or Without Ribavirin

Gregory T. Everson1; Geoffrey Dusheiko2; Eoin Coakley3; Stephen D. Shafran4; Fabien Zoulim5;

Moises Diago6; Bradley Freilich7; Ravi Ravinuthala8; Suzanne Norris9; Junyuan J. Xiong3; Roger Trinh3;

Tolga Baykal3; Yan Luo3; Mark S. Sulkowski10

1. University of Colorado Denver, Aurora, CO

2. The Royal Free Hospital, London, United Kingdom

3. AbbVie Inc., North Chicago, IL

4. University of Alberta, Edmonton, AB, Canada

5. Hospices Civils de Lyon, Lyon, France

6. Hospital Quirón de Valencia, Valenci, Spain

7. Kansas City Gastroenterology & Hepatology, Kansas City, MO

8. Consultants for Clinical Research, Cincinnati, OH

9. St. James’s Hospital, Dublin, Ireland

10.Johns Hopkins University, Baltimore, MD

Abstract #83

18

• Patients infected with GT 1a in the

PEARL-IV, SAPPHIRE-I, SAPPHIRE-II, or

TURQUOISE-II trials

• 363/1058 (25%) of GT 1a treated patients had

cirrhosis

19

90.1 90.1

96.0 96.0

0

20

40

60

80

100

All Patients Treatment Naïve

Pro

port

ion o

f patients

with S

VR

12 (

%)

3D + PBO

3D + RBV

Logistic regression:

baseline BMI and

treatment regimen

(+/- RBV) were

significant variables

for not achieving SVR

94.0

100 95.4

Relapse PR NR

12 Weeks

Prior PegIFN/RBV Response

p=0.004 p=0.006

182/

202

569/

593

182/

202

403/

420

47/

50

36/

36

83/

87

20

88.7 92.4 93.3

100

80

95.0 94.6 100 100

92.9

0

20

40

60

80

100

All Patients TreatmentNaïve

Relapse PartialResponder

NullResponder

Pro

port

ion o

f patients

with S

VR

12 (

%)

12 weeks

24 weeks

3D + RBV

Logistic regression:

IL28B TT, prior null,

North American region

and history of IDU

were significant

variables for not

achieving SVR

p=0.08 p=0.73 p=0.13

126

/14

2

115/

121

61/

66

53/

56

14/

15

13/

13

11/

11

10/

10

40/

50

39/

42

Prior PegIFN/RBV Response

21

• GT 1a patients without cirrhosis benefit from

RBV inclusion in 12 week treatment regimen

(SVR12=96%)

• GT 1a patients with cirrhosis achieved

SVR12 rates >90% with 3D + RBV regimen

but 24 weeks should be needed in

experienced patients.

22

SVR12 Rate of 98.6% in 992 HCV Genotype 1b-

Infected Patients Treated with ABT-450/r/Ombitasvir

and Dasabuvir With or Without Ribavirin

Massimo Colombo1; Ola Weiland2; Daniel E. Cohen3; Jean-Francois J. DuFour4; Hendrik Reynaert5;

Moises Diago6; Erica Villa7; Adrian Streinu-Cercel8; Wangang Xie3; Tolga Baykal3; Jeffrey Enejosa3;

Eoin Coakley3; Roger Trinh3; Thomas Podsadecki3

Abstract #1931

1. Fondazione IRCCS Cà Granda Ospedale Maggiore

Policlinico, Università degli Studi di Milano, Milan, Italy

2. Karolinska University Hospital Huddinge, Karolinska

Institutet, Stockholm, Sweden

3. AbbVie Inc., North Chicago, IL

4. Inselspital Bern, Bern, Switzerland

5. Universitair Ziekenhuis Brussel, Brussels, Belgium

6. Hospital Quirón de Valencia, Valencia, Spain

7. A.O.U. Policlinico di Modena, Modena, Italy

8. Carol Davila University of Medicine and Pharmacy, National

Institute for Infectious Diseases “Prof. Dr. Matei Bals”,

Bucharest, Romania

23

• Reporting efficacy of 3D regimen + RBV in GT 1b-

infected patients treated for 12 or 24 weeks

• Data collated from 5 Phase 3 trials

– PEARL-II, PEARL-III, SAPPHIRE-I, SAPPHIRE-II or

TURQUOISE-II

• Included 992 patients in analysis

– US: 214

– Europe: 582

– Rest of world: 196

24

• 3D alone in GT 1b noncirrhotics: 99.3% (299/301)

• 3D + RBV in GT 1b for 12 or 24 weeks: 98.3%

(679/691)

– Includes 67/68 (98.5%) with cirrhosis treated for 12 weeks

• All patients with both cirrhosis and prior PEG/RBV

null response achieved SVR12 with 3D+RBV for 12

or 24 weeks

25

• The 12 week 3D regimen with or without RBV

achieved optimal efficacy in all GT 1b-infected

patients, including those with prior null response

and/or cirrhosis.

• The addition of RBV to the 3D regimen did not

provide additional benefit in patients without

cirrhosis, nor did longer treatment duration in

patients with cirrhosis treated with 3D+RBV.

26

Interferon-Free Regimens of Ombitasvir and ABT-

450/r With or Without Ribavirin in Patients With

HCV Genotype 4 Infection:

PEARL-I Study Results

Stanislas Pol1; K. Rajender Reddy2; Tolga Baykal3; Christophe Hezode4; Tarek Hassanein5; Patrick

Marcellin6; Marina Berenguer7; Katarzyna M. Fleischer-Stepniewska8; Coleen Hall3;

Christine Collins3; Regis A. Vilchez3

1. Groupe Hospitalier Cochin-Saint Vincent De Paul,

Paris, France

2. University of Pennsylvania, Philadelphia, PA

3. AbbVie, Inc., North Chicago, IL

4. Hôpital Henri Mondor, Créteil, France

5. Southern California Liver Centers and Southern California

Research Center, Coronado, CA

6. Hopital Beaujon Inserm Crb3 - U773 - Service Hepatologie,

Clichy, France

7. Hospital Universitario La Fe, Valencia, Spain

8. EMC Instytut Medyczny Spolka Akcyjna, Wroclaw, Poland

Abstract #1928

27

• GT4 constitutes approximately 20% of all HCV infections

worldwide

• GT4 is prevalent in the Middle East and Sub-Saharan

Africa and constitutes approximately 90% of HCV

infections in Egypt

• Prevalence of GT4 is increasing in several European

countries

• Report the safety and efficacy in non-cirrhotic, treatment-

naïve and treatment-experienced GT4 patients

28

91 100

100

0

20

40

60

80

100

Ombitasvir + ABT-450/r Ombitasvir + ABT-450/r +RBV

Ombitasvir + ABT-450/r +RBV

SV

R12 (

%)

49/49 42/42 40/44

29

• Ledipasvir

– Once-daily, oral, 90-mg

NS5A inhibitor

• Sofosbuvir

– Once-daily, oral, 400-mg

NS5B inhibitor

• Ledipasvir/Sofosbuvi

r FDC

– Once-daily, oral, fixed-

dose (90/400 mg)

combination tablet

– Single-tablet regimen for

hepatitis C

LDV

NS5A

inhibitor

SOF

nucleotide

polymerase

inhibitor

LDV

NS5A

inhibitor

SOF

nucleotide

polymerase

inhibitor

30

Ledipasvir/Sofosbuvir Fixed-Dose Combination is

Safe and Efficacious in Cirrhotic Patients Who Have

Previously Failed Protease-Inhibitor Based

Triple Therapy Marc Bourlière1; Jean-Pierre Bronowicki2; Victor de Ledinghen3; Christophe Hézode4; Fabien Zoulim5;

Philippe Mathurin6; Albert Tran7; Dominique G. Larrey8; Vlad Ratziu9; Laurent Alric10; Robert H. Hyland11;

Deyuan Jiang11; Brian Doehle11; Phillip S. Pang11; William T. Symonds11; Mani Subramanian11; John G. McHutchison11;

Patrick Marcellin12; François Habersetzer13; Dominique Guyader14; Jean-Didier Grange15; Veronique Loustaud-Ratti16;

Lawrence Serfaty17; Sophie Metivier18; Vincent Leroy19; Armando Abergel20; Stanislas Pol21

Abstract #LB-6

1. Hôpital Saint Joseph, Marseilles, France

2. CHU de Nancy-Hôpital Brabois Adulte,

Vandoeuvre-lès-Nancy, France

3. CHU de Bordeaux, Pessac, France

4. Hôpital Henri Mondor, Créteil, France

5. Hôpital de La Croix Rousse, Lyon, France

6. CHRU Lille, Lille, France

7. CHU de Nice, Nice, France

8. Hôpital Saint Eloi, Montpellier, France

9. Hôpital de la Pitié Salpétrière, Paris, France

10. Hôpital Purpan, Toulouse, France

11. Gilead Science, Inc., Foster City, CA

12. Hôpital Beaujon, Clichy, France

13. Hôpitaux Universitaires de Strasbourg, Strasbourg, France

14. Hôpital Pontchaillou, Rennes, France

15. Hôpital Tenon, Paris, France

16. Hôpital Universitaire Dupuytren, Limoges, France

17. Hôpital Saint Antoine, Paris, France

18. Hôpital Purpan, Toulouse, France

19. CHU de Grenoble, Grenoble, France

20. CHU Estaing, Clermont-Ferrand, France

21. Department of Hepatology, Hôpital Cochin et Université Paris-

René Descartes, Paris, France

31

• Double-blinded

• Treatment-experienced patients with compensated

cirrhosis who did not achieve SVR following

sequential PEG/RBV and PI/PEG/RBV regimens

• 2 Arms

– Placebo 12 weeks followed by LDV/SOF + RBV for

12 weeks

– LDV/SOF + Placebo RBV for 24 weeks

32

96 97

0

20

40

60

80

100

LDV/SOF + RBV 12 Weeks LDV/SOF 24 Weeks

SV

R12 (

%)

75/77 74/77

33

• Only 2 AEs occurred at a higher frequency with

LDV/SOF compared with placebo (comparison

during first 12 weeks of placebo-controlled double

blind portion)

– Headache: 21% placebo vs 35% LDV/SOF

– Fatigue: 4% placebo vs 17% LDV/SOF

34

An Integrated Safety and Efficacy Analysis of >500

Patients with Compensated Cirrhosis Treated with

Ledipasvir/ Sofosbuvir with or without Ribavirin

Marc Bourlière1; Mark S. Sulkowski2; Masao Omata3; Stefan Zeuzem4; Jordan J. Feld5; Eric Lawitz6;

Patrick Marcellin7; Robert H. Hyland8; Xiao Ding8; Jenny C. Yang8; Steven J. Knox8; Phillip S. Pang8;

Mani Subramanian8; William T. Symonds8; John G. McHutchison8; Alessandra Mangia9;

Edward J. Gane10; K. Rajender Reddy11; Masashi Mizokami12; Stanislas Pol13; Nezam H. Afdhal14

1. Hôpital Saint Joseph, Marseilles, France

2. Johns Hopkins University, Baltimore, MD

3. Yamanashi Prefectural Hospital Organization, Yamanashi,

Japan

4. Johann Wolfgang Goethe University, Frankfurt am Main,

Germany

5. Sandra Rotman Centre for Global Health, University of

Toronto, Toronto, ON, Canada

6. Texas Liver Institute, University of Texas Health Science

Center, San Antonio, TX

7. Hôpital Beaujon, University of Paris, Paris, France

8. Gilead Science, Inc, Foster City, CA

9. Liver Unit, Casa Sollievo della Sofferenza Hospital, San

Giovanni Rotondo, Italy

10. New Zealand Liver Transplant Unit, Auckland City Hospital,

Auckland, New Zealand

11. University of Pennsylvania, Philadelphia, PA

12. Research Center for Hepatitis and Immunology, National

Center for Global Health and Medicine, Chiba, Japan

13. Department of Hepatology, Université Paris-René Descartes,

Paris, France

14. Beth Israel Deaconess Medical Center, Boston, MA

Abstract #82

35

• 513 patients with GT 1, compensated cirrhosis

• Pooled data from Phase 2 and 3 LDV/SOF ±

RBV studies

– LONESTAR, ELECTRON, ELECTRON-2, 337-0113,

ION-1, ION-2, SIRIUS

36

Patients, % Treatment

Naïve

(n=161)

Treatment

Experienced

(n=352)

Total

(n=513)

Male 63% 68% 67%

Black 8% 4% 5%

Asian 17% 15% 15%

GT 1a 53% 63% 60%

Prior PI Failure NA 68% 47%

Region

US 50% 31% 37%

Ex-US 50% 69% 63%

37

96 95 98

0

20

40

60

80

100

Overall 12 Weeks 24 Weeks

SV

R12 (

%)

188/191 305/322 493/513

38

• Among treatment-experienced patients, 12 weeks

of LDV/SOF without RBV resulted in only 90%

SVR rate

• Adding RBV or extending treatment duration

increased this rate to ≥96%

• Platelet count <75 x 103/uL was associated with a

lower SVR rate among treatment-experienced

patients with cirrhosis

39

Ledipasvir/Sofosbuvir with Ribavirin for the

Treatment of HCV in Patients with Decompensated

Cirrhosis: Preliminary Results of a Prospective,

Multicenter Study

Steven L. Flamm1; Gregory T. Everson2; Michael Charlton3; Jill M. Denning4; Sarah Arterburn4;

Theo Brandt-Sarif4; Phillip S. Pang4; John G. McHutchison4; K. Rajender Reddy5; Nezam H. Afdhal6

Abstract #239

1. Northwestern Feinberg School of Medicine, Chicago, IL

2. University of Colorado Denver, Aurora, CO

3. Intermountain Medical Center, Murray, UT

4. Gilead Sciences, Raleigh, NC

5. University of Pennsylvania School of Medicine, Philadelphia, PA

6. Beth Israel Deaconess Medical Center, Boston, MA

40

• 108 GT 1 or 4 treatment naïve or treatment experienced

patients with decompensated cirrhosis (Child-Pugh class

B[7-9]) or C[10-12])

• Inclusion/exclusion

– No history of major organ transplant, including liver

– No HCC

– Total bili <10 mg/dL, hemoglobin >10 g/dL

– CLcr >40 mL/min, platelets >30,000 x 103/uL

• LDV/SOF (ledipasvir/sofosbuvir)+ RBV for 12 or 24 weeks

41

87 87 86 89 89 90

0

20

40

60

80

100

Overall CPT B CPT C

12 Weeks

24 Weeks

45/52 42/47 26/30 24/2

7 19/22 18/2

0

SV

R1

2 (

%)

42

Related SAEs: Anemia, hepatic encephalopathy, peritoneal hemorrhage

CPT B CPT C

Patients, %

12 Weeks

(n=30)

24 Weeks

(n=29)

12 Weeks

(n=23)

24 Weeks

(n=26)

Adverse Events (AE) 97% 93% 100% 100%

Grade 3-4 AE 7% 28% 26% 42%

Serious AE 10% 34% 26% 42%

Serious and Related AEs 7% 0 0 8%

Treatment discontinuation

due to AE 0 3% 0 8%

Death 3% 7% 9% 4%

43

• Extending treatment duration to 24 weeks did not

increase SVR rate

• LDV/SOF + RBV was generally safe and well

tolerated in decompensated cirrhotics

44

High Efficacy of LDV/SOF Regimens for 12 Weeks

for Patients with HCV Genotype 3 or 6 Infection

E. J. Gane1; R. H. Hyland2; D. An2; E. S. Svarovskaia2; P. S. Pang2; W. T. Symonds2;

J. G. McHutchison2; C. A. Stedman3

Abstract #LB-11

1. Auckland Clinical Studies, Auckland, New Zealand

2. Gilead Science, Inc., Foster City, CA, United States

3. Christchurch Clinical Studies Trust, Christchurch, New Zealand

45

82 89

73

96

0

20

40

60

80

100

Pati

en

ts (

%)

Overall No Cirrhosis Cirrhosis

GT 3 GT 6

41/50 25/28 16/22 24/26

LDV/SOF + RBV

12 Weeks

LDV/SOF

12 Weeks

46

• LDV/SOF + RBV for 12 weeks resulted in

SVR12 rates of 73% and 89% in treatment-

experienced GT3 patients with and without

cirrhosis, respectively

– Similar SVR12 to previous reports of SOF + RBV

(24 weeks) and SOF + PEG/RBV (12 weeks)

• LDV/SOF for 12 weeks without RBV is first

reported safe, effective, all-oral regimen for

GT6 patients

47

All Oral Treatment for Genotype 4 Chronic Hepatitis

C Infection with Sofosbuvir and Ledipasvir:

Interim Results from the NIAID SYNERGY Trial

Rama Kapoor1; Anita Kohli1; Sreetha Sidharthan2; Zayani Sims2; Tess L. Petersen2; Anu Osinusi3;

Amy K. Nelson3; Rachel Silk1; Colleen Kotb1; Kate Sugarman4; Brian P. Lam5; Phillip S. Pang6;

Mani Subramanian6; John G. McHutchison6; Henry Masur2; Shyam Kottilil3; Vinod K. Rustgi7

Abstract #240

1. Leidos Biomedical Research, Inc. (formerly SAIC–Frederick, Inc.), Frederick National Laboratory for Cancer Research,

Frederick, MD

2. Critical Care Medicine Department, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, MD

3. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health,

Bethesda, MD

4. Unity Health Care, Inc., Washington, DC

5. Center for Liver Diseases, Inova Fairfax Medical Campus, Falls Church, VA

6. Gilead Sciences Inc., Foster City, CA

7. University of Pittsburgh Medical Center, Pittsburgh, PA

48

• Patient population

– GT4 infected patients with any stage of liver fibrosis

– Treatment naïve or treatment experienced

• Regimen

– SOF/LDV for 12 weeks

• SVR12: 19 of 20 patients (95%)

49

Retreatment of Patients Who Failed Prior

Sofosbuvir- Based Regimens with All Oral

Fixed-Dose Combination Ledipasvir/Sofosbuvir

Plus Ribavirin for 12 Weeks

David L. Wyles1; Paul J. Pockros2; Jenny C. Yang3; Yanni Zhu3; Phillip S. Pang3;

John G. McHutchison3; Steven L. Flamm4; Eric Lawitz5

Abstract #235

1. University of California, San Diego, La Jolla, CA

2. Scripps Translational Science Institute, La Jolla, CA

3. Gilead Sciences, Inc, Foster City, CA

4. Northwestern University, Chicago, IL

5. The Texas Liver Institute, San Antonio, TX

50

• Evaluate whether LDV/SOF + RBV for 12 weeks is

effective in GT 1 treatment-experienced patients

who have failed prior SOF-based therapy

• 51 patients

– 16% African American

– 59% GT 1a

– 29% cirrhosis

– Prior HCV treatment • SOF + PEG/RBV: 49%

• SOF ± RBV*: 41%

• SOF placebo**: 5%

51

• 50/51 (98%) of patients achieved SVR12

• 1 patient who failed was a GT 3a patient who

relapsed (inadvertently genotyped as GT 1a

at baseline)

• No patients had SOF-associated variant,

S282T, detected at baseline

– 2 patients had NS5B treatment-emergent variant

L159F at baseline and achieved SVR

52

Once Daily Sofosbuvir with GS-5816 for 8 Weeks

with or without Ribavirin In Patients with HCV

Genotype 3 without Cirrhosis Result in High Rates

of SVR12: The ELECTRON2 Study

Edward J. Gane1; Robert H. Hyland2; Di An2; John McNally2; Diana M. Brainard2; William T. Symonds2;

John G. McHutchison2; Catherine A. Stedman3

1. Auckland Clinical Studies, Auckland, New Zealand

2. Gilead Science, Inc, Foster City, CA

3. Christchurch Clinical Studies Trust, Christchurch, New Zealand

Abstract #79

53

• Sofosbuvir (SOF) is an approved nucleotide polymerase

inhibitor with activity against HCV GT 1-6

• GS-5816 is an investigational inhibitor of the HCV NS5A

protein with picomolar antiviral activity across all HCV

genotypes 1-6

• In a Phase 2 study, 12 week treatment with SOF + GS-5816

at a dose of 25 or 100 mg/day with or without RBV was

found to be safe and effective

• Evaluate safety and efficacy in treatment naïve non-cirrhotic

GT 3 patients when administered for 8 weeks

54

SV

R12 (

%)

100 88 96 100

0

20

40

60

80

100

27/27

GS-5816, mg

RBV

21/24 26/27 26/26

25

‒

25

+

100

‒

100

+

55

• SOF + GS-5816 (25 mg or 100 mg) ± RBV for 8

weeks resulted in high SVR12 rates in treatment

naïve non-cirrhotic GT3 patients

• Regimen was well tolerated with no identified

safety signal due to SOF or GS-5816

• SOF 400 mg + GS-5816 100 mg have been co-

formulated in a fixed-dose combo for Phase 3

56

Efficacy and safety of MK-5172 and MK-8742 ±

ribavirin in hepatitis C genotype 1 infected patients

with cirrhosis or previous null response: Final

results of the C-WORTHY Study (Parts A and B) Eric Lawitz1; Edward J. Gane2; Brian Pearlman3; Edward Tam4; Wayne Ghesquiere5; Dominique Guyader6;

Laurent Alric7; Jean-Pierre Bronowicki8; Lorenzo Rossaro9; William Sievert10; Reem H. Ghalib11;

Luis A. Balart12; Fredrik Sund13; Martin Lagging14; Frank Dutko15; Anita Y. Howe15; Melissa Shaughnessy15;

Peggy Hwang15; Janice Wahl15; Michael Robertson15; Barbara A. Haber15

1. The Texas Liver Institute, University of Texas Health Science

Center, San Antonio, TX

2. Auckland Clinical Studies, Grafton, Auckland, New Zealand

3. Atlanta Medical Center, Atlanta, GA

4. LAIR Centre, Vancouver, BC, Canada;

5. Vancouver Island Health Authority, Victoria, BC, Canada

6. Department of Hepatology, Rennes University Hospital,

Rennes 1 University, Rennes, France

7. CHU Purpan, Digest Dept., UMR 152, Toulouse 3 University,

Toulouse, France

8. INSERM U954, Centre Hospitalier Universitaire de Nancy,

Université de Lorraine, Vandoeuvre-les-Nancy, France

9. University of California, Davis Medical Center, Sacramento,

CA

10.Monash University and Monash Health, Melbourne, VIC,

Australia

11.Texas Clinical Research Institute, Arlington, TX

12.Tulane University School of Medicine, New Orleans, LA

13. Infectious Diseases, Uppsala University, Uppsala, Sweden

14. Institute of Biomedicine, University of Gothenburg,

Gothenburg, Sweden

15.Merck & Co., Inc., Whitehouse Station, NJ

Abstract #196

57

• Grazoprevir (MK-5172) is a highly potent HCV-

specific NS3/4A protease inhibitor

• Elbasvir (MK-8742) is a highly potent HCV-specific

NS5A inhibitor

Treatment-naive, non-cirrhotic 12 weeks ± RBV

(n = 65) Pt. A

Treatment-naive Non-cirrhotic

8-12 weeks ± RBV (n = 94) Pt.B

Treatment-naive Cirrhotic

12-18 weeks ± RBV (n = 123) Pt.B

HIV/HCV Co-infected Non-cirrhotic

12 weeks ± RBV (n = 59) Pt.B

Null Responders Cirrhotic / Non-cirrhotic

12-18 weeks ± RBV (n = 130) Pt.B

58

90 97 97 94 94 91 100 97

0

20

40

60

80

100

SV

R12 (

%,

95%

CI)

Treatment-naïve patients with

cirrhosis

PR-Nulls with or without

cirrhosis

12 Weeks 18 Weeks 12 Weeks 18 Weeks

+ RBV No

RBV + RBV

No

RBV + RBV

No

RBV + RBV

No

RBV

59

• SVR12 was 92% (23/25) in null responders with

cirrhosis treated for 12 weeks with grazoprevir +

elbasvir ± RBV

• High efficacy without RBV and with only

12 weeks treatment

• Grazoprevir + elbasvir were generally safe and

well tolerated

60

C-SWIFT: Grazoprevir (MK-5172) + Elbasvir (MK-

8742) +Sofosbuvir in Treatment-naïve Patients With

Hepatitis C Virus Genotype 1 Infection, With and

Without Cirrhosis, for Durations of 4, 6, or 8 Weeks

(Interim Results)

Eric Lawitz1; Fred Poordad1; Julio A. Gutierrez1; Barbara Evans2; Peggy Hwang2; Anita How2;

Hwa-Ping Feng2; Michael Robertson2; Janice Wahl2; Eliav Barr2; Barbara Haber2

1. The Texas Liver Institute, University of Texas Health Science Center, San Antonio TX, USA

2. Merck & Co.

Abstract #LB-33

61

38.7

86.7 80

94.7

0

20

40

60

80

100

4 weeks 6 weeks 6 weeks 8 weeks

SV

R8 (

%)

28/31 26/34 16/32 26/30

________________________________

Noncirrhotic ________________________________

Cirrhotic

62

• Combined regimens of 3 potent antivirals may be

able to shorten treatment duration to 6-8 weeks

among cirrhotic and noncirrhotic GT1 infected

patients

• Factors that may have impacted likelihood of SVR

in 4 and 6 week arms

– GT 1a vs 1b

– Baseline viral load

– IL28B status

– PK of component medicines in the regimen

63

All-oral 12-week Combination Treatment With Daclatasvir

(DCV) and Sofosbuvir (SOF) in Patients Infected with

HCV Genotype (GT) 3: ALLY-3 Phase 3 Study

D. R. Nelson1; J. N. Cooper2; J. P. Lalezari,3; E. Lawitz4; P. J. Pockros5; N. Gitlin6; B. Freih.ch7;

Z. Younes8; W. Harlan9; R. H. Ghall10; G. I. Oguchi11; P. J. Thuluvath12; G. Ortiz-Lasanta13;

M. Rabinovitz14; D. Bernstein15; M. Bennett16; T. Hawkins17; N. Ravendhran8; A. M. Sheikh19;

P. Varunok; K. V. Kowdley; D. Hennicken; F. McPhee; K. Rana; E. A. Hughes22

1. University of Florida, Gainesville, FL, United States

2. !nova Fairfax Hospital, Falls Church, VA, United States

3. Quest Clinical Research, San Francisco, CA, United States

4. Texas Liver Institute, University of Texas Health Science

Center, San Antonio, TX, United States

5. Scripps Clinic, La Jolla, CA, United States

6. Atlanta Gastroenterology Associates, Atlanta, GA, United States

7. Kansas City Research Institute, Kansas City, MO, United States

8. Gastro One, Germantown, TN, United States

9. Asheville Gastroenterology Associates, Asheville, NC, United

States

10. Texas Clinical Research Institute, Arlington, TX, United States

11. Midland Florida Clinical Research Center, DeLand, FL, United

States

12. Mercy Medical Center, Baltimore, MD, United States

13. Fundacion de Investigacion de Diego, Santurce, Puerto Rico,

United States

14. University of Pittsburgh, Pittsburgh, PA, United States

15. Hofstra North Shore-Long Island Jewish School of Medicine,

Manhasset, NY, United States

16. Medical Associates Research Group, San Diego, CA, United

States

17. Southwest CARE Center, Santa Fe, NM, United States

18. Digestive Disease Associates, Baltimore, MD, United States

19. Gastrointestinal Specialists of Georgia, Marietta, GA, United

States

20. Premier Medical Group of Hudson Valley, Poughkeepsie, NY,

United States

21. Swedish Medical Center, Seattle, WA, United States

22. Bristol-Myers Squibb Research and Development, Princeton,

NJ, United States

Abstract #LB-3

64

• HCV genotype (GT) 3 is common worldwide and

remains a significant disease burden

• GT 3 infection is associated with increased risk of

fibrosis progression, steatosis, and hepatocellular

carcinoma in patients with cirrhosis

• Current therapies for patients with GT 3 infection

include

– US and Europe • 24 week sofosbuvir (SOF) + ribavirin (RBV)

• 12 week SOF + PEG/RBV

– Europe • 24-week daclatasvir (DCV) + SOF ± RBV

65

• Two cohorts consisting of GT 3 treatment naive or

treatment experienced patients received open-label

DCV + SOF once daily for 12 weeks

• 21% of patients were cirrhotic

66

90 86

0

20

40

60

80

100

Treatment Naive Treatment Experienced

SV

R12,

%

91/101 44/51

67

SV

R12, %

Overall

96 97 94

63 58

69

0

20

40

60

80

100

Treatment-

naive

Treatment-

experienced

Present Absent

105/109 73/75 32/34 20/32 11/19 9/13

Present Absent Present Absent

68

• DCV + SOF for 12 weeks achieved high SVR rates

– 90% in treatment naïve

– 86% in treatment experienced

– 96% in non-cirrhotics

– 63% in cirrhotics (further optimization being evaluated)

• DCV + SOF was safe and well tolerated

69

All-oral fixed-dose combination therapy with

daclatasvir/asunaprevir/BMS-791325, ± ribavirin, for

patients with chronic HCV genotype 1 infection and

compensated cirrhosis: UNITY-2 Phase 3 SVR12 results

A. Muir1; F. Poordad2; J. P. Lalezari3; G. T. Everson4; G. J. Dore5; P. Kwo6; C. Hezode7;

P. J. Pockros8; A. Tran9; A. Ramp10; R. Yang11; E. A. Hughes11; E. S. Swenson12; P. D. Yin12

1. Duke Clinical Research Institute, Duke University School of

Medicine, Durham, NC, United States

2. Texas Liver Institute, University of Texas Health Science

Center, San Antonio, TX, United States

3. Quest Clinical Research, San Francisco, CA, United States

4. University of Colorado School of Medicine, Denver, CO,

United States

5. Kirby Institute , UNSW Australia, Sydney, NSW, Australia

6. Indiana University School of Medicine, Indianapolis, IN,

United States

7. Hopital Henri Mondor , University Paris-Est, Creteil, Creteil,

France

8. Scripps Clinic, La Jolla, CA, United States

9. Centre Hospitalier Universitaire de Nice, Nice, France

10.University of British Columbia, Vancouver, BC, Canada

11.Bristol-Myers Squibb, Princeton, NJ, United States

12.Bristol-Myers Squibb, Wallingford, CT, United States

Abstract #LB-2

70

• All-oral DCV-TRIO regimen

– Daclatasvir (DCV)

• NS5A inhibitor

• Approved in Europe and Japan; under review in US

– Asunaprevir (ASV)

• NS3 protease inhibitor

• Clinical data in GT 1 and GT 4

– Beclabuvir (BCV, BMS-791325)

• Non-nucleoside NS5B polymerase inhibitor

• Clinical data in GT 1 and GT 4

• UNITY-2 Study

– DCV/ASV/BCV twice daily, fixed dose combo ± RBV in GT 1 treatment

naïve and treatment experienced compensated cirrhotics

71

93 98

87 93

0

20

40

60

80

100

DCV TRIO DCV TRIO +RBV

DCV TRIO DCV TRIO +RBV

SV

R12 (

%)

53/57

________________________________

Treatment Naive ________________________________

Treatment Experienced

54/55 39/45 42/45

72

90 97

86 91

100 100

90

100

0

20

40

60

80

100

DCV TRIO DCV TRIO +RBV

DCV TRIO DCV TRIO +RBV

SV

R12 (

%)

GT 1a

GT 1b

36/

40

17/

17

________________________________

Treatment Naive

________________________________

Treatment Experienced

38/

39

30/

35

32/

35 15/

15

9/

10

10/

10

73

• DCV-TRIO ± RBV was safe and well tolerated with

low rates of SAEs and AE discontinuations

• Most commonly observed AEs with DCV-TRIO

were headache, nausea, diarrhea, and fatigue