Rafael Esteban, MD Barcelona, Spain · 2015. 1. 13. · Rafael Esteban, MD Barcelona, Spain This...

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Rafael Esteban, MDBarcelona, Spain

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

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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

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• 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


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


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• 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


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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

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• 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

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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.


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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


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• 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


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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

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• 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


Error bars represent 95% confidence intervals.

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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



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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



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• 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

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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

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• 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


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


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

Rafael Esteban, MD Barcelona, Spain · 2015. 1. 13. · Rafael Esteban, MD Barcelona, Spain This...

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