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Geoffrey Dusheiko, MDLondon, UK
This activity is supported by an independent medical education grant from AbbVie, Bristol-Myers Squibb and Gilead Sciences
Oral Fixed-Dose Combination Ledipasvir/Sofosbuvir With or Without Ribavirin for 12 or 24 Weeks in Treatment-Experienced Genotype 1 HCV-Infected Patients:
The Phase 3 ION-2 StudyNezam 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 ontaining a NS3/4A protease inhibitor oad inclusion criteria
– Targeted 20% enrollment of patients with cirrhosis– No upper age or BMI limit– Platelet count ≥50,000/mm3, no neutrophil minimum40 patients randomized 1:1:1:1 across four armsratified 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
ms were balanced with respect to demographics and baseline characteristics
12 Weeks 24 WeeksLDV/SOF
n=109LDV/SOF+RBV
n=111LDV/SOF
n=109LDV/SOF+RBV
n=111Mean 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)
GT 1a, n (%) 86 (79) 88 (79) 85 (78) 88 (79)Mean HCV RNA,og10 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)
r bars represent 95% confidence intervals.
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
ars 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 Weeks
LDV/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
ars represent 95% confidence intervals.
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
tz E, et al. Lancet. 2014;383:515-23.
hort, safe, and effective interferon- and ribavirin-free eatment options for patients with chronic HCV GT 1 fection are currently lacking
DV/SOF ± RBV for 8 weeks and LDV/SOF for 12 weeks emonstrated high SVR rates in the Phase 2 LONESTAR tudy in treatment-naïve HCV patients without cirrhosis1
o evaluate whether LDV/SOF for 8 weeks is effective for CV treatment-naïve, non-cirrhotic, GT 1 patients or if RBV r a longer treatment duration of 12 weeks is required to chieve high SVR rate
T 1 treatment-naïve patients without cirrhosisroad inclusion criteria– No upper age or BMI limit– Opiate substitution therapy allowed47 patients randomized 1:1:1 across three armstratified 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
bars represent 95% confidence intervals.
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
Safety and Efficacy of Treatment With the Interferon-free, Ribavirin-free Combination of Sofosbuvir+GS-5816 For 12
Weeks in Treatment Naïve Patients With Genotype 1-6 HCV Infection
G.T. Everson1, T.T. Tran2, W.J. Towner3, M.N. Davis4, D. Wyles5, R. Nahass6, J. McNally7,M. Brainard7, L. Han7, B. Doehle7, E. Mogalian7, W.T. Symonds7, J.G. McHutchison7, T. Morgan8,
R.T. Chung9
niversity of Colorado Denver, Aurora, CO, 2Cedars-Sinai Medical Center, 3Kaiser Permanente, Los les, CA, 4Digestive CARE, South Florida Center of Gastroenterology, LLC, Wellington, FL, 5University
California, San Diego, CA, 6ID CARE, Hillsborough, NJ, 7Gilead Sciences, Inc., Foster City, 8VA Long Beach, Long Beach, CA, 9Massachusetts General Hospital, Boston, MA, United States
GT 1(N=55)
GT 3(N=54)
GT 2-6(N=45)
SOF + GS-5816 25 mg
SOF + GS-5816 100 mg
SOF + GS-5816 25 mg
SOF + GS-5816 100 mg
SOF + GS-5816 25 mg
SOF + GS-5816 100 mg
Wk 0 Wk 12 Wk 24
SVR12
pen label– SOF 400 mg + GS-5816 25 mg for 12 weeksor– SOF 400 mg + GS-5816 100 mg for 12 weeksreatment-naïve patients with HCV GT 1-6 without cirrhosiso ribavirin administered
96 91 93100 100 93
0
20
40
60
80
100
SOF + GS-5816 25 mg SOF + GS-5816 100 mg
GT 1 GT 2 GT 3
26/27 28/28 10/11 10/10 25/27 25/27
100 100 100
86
100
0
20
40
60
80
100
SOF + GS-5816 25 mg SOF + GS-5816 100 mg
GT 4 GT 5 GT 6
7/7 6/7 10/10 4/4 5/51/1
OF + GS-5816 for 12 weeks resulted in SVR12 ates >90% in all HCV genotypes (1-6)– Relapse was observed more often in patients treated with
GS-5816 25 mg (N=3) compared to GS-5816 100 mg (N=1)he presence of pre-treatment NS5A variants was ot predictive of failure to achieve SVR 12OF + GS-5816 was well tolerated with no iscontinuations due to AEshe combination of SOF 400 mg and GS-5816 100
mg is being evaluated in treatment-experienced atients and patients with cirrhosis
SAPPHIRE-I: Phase 3 Placebo-Controlled Study of nterferon-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
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; asabuvir, 250 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=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%
455/473 307/322 148/151
GT1a GT1b
ent, n/N (%)3D + RBV(N=473)
R12 455/473 (96.2)
n-SVR12 18/473 (3.8)
irologic failure
Breakthrough 1/473 (0.2)
Relapse 7/463 (1.5)
rematurely discontinued study drug* 7/473 (1.5)
ost to follow-up after completion of treatment 3/473 (0.6)
reakthrough and relapse rates of 0.2% and 1.5%, respectivelynts (n=7) who prematurely discontinued without breakthrough; 2 due to adverse events, 5 withdrew consent/ follow-up.
RQUOISE-II: SVR12 Rates of 92%-96% in 380 Hepatitis C us Genotype 1-Infected Adults With Compensated Cirrhosis eated With ABT-450/r/ABT-267 and ABT-333 Plus Ribavirin
(3D+RBV)F. Poordad1, C. Hezode2, R. Trinh3, K.V. Kowdley4, S. Zeuzem5, K. Agarwal6, M.L. Shiffman7,
H. Wedemeyer8, 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; dasabuvir, 250 mg BID
BV: 1000-1200 mg daily according to body weight (<75 kg nd >75kg, respectively)
ay 0 Week 24Week 12
SVR12
SVR12
3D + RBV(N=208)
3D + RBV(N=172)
All patients to be followed through 48 weeks post-treatment
0
20
40
60
80
100
SVR
12, %
Pat
ient
s
12 Weeks3D + RBV
91.8
191/208
95.9
165/172
24 Weeks3D + RBV
P=0.089
0
20
40
60
80
00 92.2
12-week arm24-week arm
92.9
Naïve Prior RelapseResponse
3D + RBV
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
Results Of The Phase 2 Study M12-999:Interferon-Free Regimen Of ABT-450/r/ABT-267+ABT-
333+Ribavirin In Liver Transplant Recipients With Recurrent HCV Genotype 1 Infection
. Kwo1, P. Mantry2, E. Coakley3, H. Te4, H. Vargas5, R. Brown Jr.6, F. Gordon7, J. Levitsky8, N. Terrault9, J. Burton Jr10, W. Xie3, C. Setze3, P. Badri3, R.A. Vilchez3, X. Forns11
iana University, Indianapolis, IN, 2The Liver Institute at Methodist Dallas Medical Center, Dallas, TX, bbVie Inc., North Chicago, 4University of Chicago Medicine, Chicago, IL, 5Mayo Clinic, Phoenix, AZ, umbia University Medical Center Center for Liver Disease and Transplantation, New York, NY, 7Lahey pital & Medical Center, Burlington, MA, 8Northwestern University Comprehensive Transplant Center,
ago, IL, 9University of California, San Francisco, San Francisco, CA, 10University of Colorado, Denver, urora, CO, United States, 11Liver Unit, Hospital Clinic, IDIBAPS and CIBEREHD, Barcelona, Spain
D: co-formulated ABT-450/r/ombitasvir, 150 mg/100 mg/25 mg QD; dasabuvir, 250 mg BID
RBV: dosing was managed at the discretion of the nvestigator and closely monitored per protocol
ay 0 Week 24
SVR12
To Week 72
3D + RBV(N=34)
ased on previous drug-drug interaction findings, ecommended dosing during 3D treatment was:– TAC
• 0.5 mg once weekly or
• 0.2 mg every 3 days
– CYA• 1/5 of the daily pre-3D treatment dose given once daily
o patient had breakthroughne patient had a relapse (post-treatment day 3)
At the time of relapse, this patient had R155K in NS3 protease, M28T+Q30R in NS5A, and G554S+G557R in NS5B, none of which were present at baseline
0
20
40
60
80
100100%
34/34
97.0%
34/34
100% 96.2%
32/33 25/26
SVR4 SVR12RVR(Week 4)
EOTR(Week 24)
n IFN-free, 24-week regimen of ABT-450/r/ombitasvir + asabuvir + RBV achieved high response rates in
mmunosuppressed liver transplant recipients with recurrent CV GT1 infection
n this on-going study:– 100% achieved RVR (34/34) and EOTR (34/34)
– 97.0% (32/33) achieved SVR4 and 96.2% (25/26) achieved SVR12
he regimen was generally well tolerated with 1 patient scontinuing study drug due to AEs– No deaths, graft losses, or episodes of rejection
NI dosing was manageable over the period of the study
Results From the Phase 2 PEARL-I Study: nterferon-Free Regimens of ABT-450/R + ABT-267 With or ithout Ribavirin in Patients With HCV Genotype 4 Infection
Hezode1, P. Marcellin2, S. Pol3, T. Hassanein4, K. Fleischer-Stepniewska5, T. Baykal6, T. Wang6,S.S. Lovell6, T. Pilot-Matias6, R.A. Vilchez6
tance Publique Hopitaux de Paris, Paris, 2Hopital Beaujon Inserm Crb3 - U 773 - Service Hepatologie, y, 3Groupe Hospitalier Cochin-Saint Vincent de Paul, Paris, France, 4Southern California Liver Centers Southern California Research Center, Coronado, CA, United States, 5EMC Instytut Medyczny Spolka
Akcyjna, Wroclaw, Poland, 6AbbVie Inc., North Chicago, IL, United States
bstudy 1*Cirrhosis
bstudy 2*mpensatedhosis
ned number of patients: 40 per treatment arm450/r (150/100 mg qd); ombitasvir (25 mg QD); RBV (weight-based 1000 or 1200 mg/day divided BID)
atients followed through 48 weeks post-treatment
Group 1 (GT4)(n=44)
Group 2 (GT1b)(n=42)
Group 3 (GT1b)(n=40)
Group 4 (GT4)(n=42)
Group 5 (GT4)
Group 6 (GT4)(n=49)
Baseline Week 12 Week 24
ABT-450/r + OmbitasvirTreatment-Naïve
ABT-450/r + OmbitasvirNull Responders
ABT-450/r + Ombitasvir + RBVTreatment-Naïve
ABT-450/r + OmbitasvirPartial/Null Responders & Relapsers
ABT-450/r + Ombitasvir + RBVPartial/Null Responders & Relapsers
Group 7 (GT1b)(n=47)
Group 8 (GT1b)(n=52)
ABT-450/r + OmbitasvirTreatment-Naïve
ABT-450/r + OmbitasvirPartial/Null Responders & Relapsers
ABT-450/r + OmbitasvirTreatment-Naïve
0
20
40
60
80
00 97.7%
ABT-450/r + Ombitasvir(N=44)
ABT-450/r + Ombitasvir+ RBV(N=42)
SVR4
SVR12
RVR (Week 4)
EOTR (Week 12)
95.5% 93.2% 90.9%97.6% 100% 100% 100%
4344
4244
4144
4044
4142
4242
4242
4242
0
20
40
60
80
00
ABT-450/r + Ombitasvir + RBV(N=49)
100% 100% 100%
49/49 49/49 37/37
SVR4
RVR (Week 4)
EOTR (Week 12)
All-oral, IFN-free, 12-week regimens of ABT-450/r + ombitasvir resulted in:
– High SVR12 rates in treatment-naïve HCV GT4-infected patients• 90.9% with ABT-450/r + ombitasvir• 100% with ABT-450/r + ombitasvir + RBV
– An SVR4 rate of 100% in treatment-experienced patients receiving ABT-450/r + ombitasvir + RBV
2-week regimens of ABT-450/r + ombitasvir +/-RBV were generally well-tolerated, with no study
rug discontinuations or interruptions due to AEs, nd few decreases in hemoglobin <10 g/dL
Safety and Efficacy of the All-oral Regimen of MK-5172/MK-8742 + Ribavirin in Treatment-naïve, Non-cirrhotic Patients With Hepatitis C Virus Genotype 1
Infection: The C-WORTHy StudyHezode1, L. Serfaty2, J.M. Vierling3, M. Kugelmas4, B. Pearlman5, W. Sievert6, W. Ghesquiere7,Zuckerman8, F. Sund9, M. Shaughnessy10, P. Hwang10, J. Wahl10, M.N. Robertson10, B. Haber10
epartment of Hepatology-Gastroenterology, Henri Mondor Hospital, University of Paris-Est, Creteil, troenterology and Hepatology, H_pital Saint Antoine, APHP and INSERM UMR_938, Universit_ Pierre Marie Curie, Paris, France, 3Hepatology, Baylor College of Medicine, Houston, TX, 4South Denver oenterology, PC, Englewood, CO, 5Center for Hepatitis C, Atlanta Medical Center, Atlanta, GA, United
ates, 6Gastrointestinal and Liver Unit, Monash University, Clayton, VIC, Australia, 7Vancouver Island h Authority, Victoria, BC, Canada, 8Carmel Medical Center, Technion Faculty of Medicine, Haifa, Israel, ectious Diseases, Uppsala University Hospital, Uppsala, Sweden, 10Merck, Whitehouse Station, NJ,
United States
o assess the efficacy/safety of an 8- to 12-week regimen of MK-5172 + K-8742 ± weight-based ribavirin in treatment-naïve, noncirrhoticatients with HCV G1 infection
ey inclusion/exclusion criteria:– Treatment-naïve patients ≥ 18 years old with chronic HCV G1a or G1b infection– Liver biopsy or noninvasive test (METAVIR F0-F3)– Minimum baseline hemoglobin: 12 g/dL (females) or 13 g/dL (males)– HIV and hepatitis B virus negative– Alanine aminotransferase (ALT) as aspartate aminotransferase (AST) <350 IU/L
Treatment-naïve, noncirrhotic12 weeks ± RBV
(n=65)
atment-naïve oncirrhoticweeks ± RBV(n=94)
Treatment-naïveCirrhotic
12-18 weeks ± RBV(n=123)
Null respondersCirrhotic/noncirrhotic
12-18 weeks ± RBV(n=130)
HIV/HCV coinfectedNoncirrhotic
12 weeks ± RBV(n=59)
ustained virologic response; TW = treatment week.
RBV-Containing Regimen RBV-Free Regimen
MK-5172 (100 mg)MK-8742 (20 mg)+ RBV
MK-5172 (100 mg)MK-8742 (50 mg)+ RBV
MK-5172 (100 mg)MK-8742 (50 mg)+ RBV
MK-5172 (100 mg)MK-8742 (50 mg)
MK-5172 (100 mg)MK-8742 (50 mg)
MK-5172 (100 mg)MK-8742 (50 mg)+ RBV
PART ASVR24
(AASLD 2013)
PART BFollow-up ongoing
SVR4/8
at ≥SVR4(28/30 SVR8)
100% at SVR8
Study Week
G1a/bN=25
G1a/bn=27
G1bn=13
G1an=30
G1a/bn=33
G1an=31
D1 TW4 TW8 TW12 SVR4 SVR8 SVR12 SVR24
100 100
83
95 96 94100 100 98
0
25
50
75
00
Treatment Week 4 End of Treatment SVR
8 weeks with RBV 12 weeks with RBV 12 weeks (no RBV)
: 100% of patients have completed SVR24; Part B: 8-week arm, 93% of patients have completed SVR8; ek arms, 100% of patients have completed SVR8; 2 patients (Part A), 2 patients (Part B) discontinued early re counted as failures).
4-24
30/30 81/85 44/44 30/30 82/85 44/44 25/30 80/85 43/44
fficacy
– MK-5172/MK8742 once daily with or without RBV for 12 weeks is highly efficacious with a SVR of 94%-98%
– MK-5172/MK-8742 + RBV for 8 weeks in patients with HCV G1a infection had an SVR44/8 of 83%
– Most common type of virologic failure was relapse after a treatment duration of 8 weeks
afety
– All treatment regimens were generally safe and well-tolerated
– There were no early discontinuations due to drug-related Aes
– No grade 3 or 4 laboratory abnormalities
fficacy and Safety of the All-Oral Regimen, MK-5172/MK-8742 +/- RBV For 12 Weeks in GT1 HCV/HIV Co-Infected
Patients: The C-WORTHY Study
k Sulkowski1, Josep Mallolas2, Marc Bourliere3, Jan Gerstoft4, Oren Shibolet5, Ronald Nahass6, Edwin DeJesus7, Melissa Shaughnessy8, Peggy Hwang8, Barbara Haber8
ohns Hopkins University School of Medicine, Baltimore, MD, USA; 2Hospital de Dia. Enfermedadesiosas, Barcelona, Spain; 3Service d'hépato-gastroentérologie, Hôpital Saint-Joseph, Marseille, France;
epartment of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark; 5Liver Unit, Department of stroenterology, Tel-Aviv Medical Center, Tel-Aviv, Israel; 6ID Care, Hillsborough, NJ, USA; 7Orlando
Immunology Center, Orlando, Florida; 8Merck & Co., Inc., Whitehouse Station, NJ, USA.
obally, ~7 million patients are co-infected with HIV and HCV(1)
V/HCV co-infected patients have a higher rate of progression to cirrhosis and hepatic compensation than HCV mono-infected patients(1-4)
K-5172 and MK-8742 can be dosed with raltegravir + dual NRTI (tenofovir or abacavir + tricitabine or lamivudine) without dosage adjustments
K-5172/MK-8742 has the potential to provide an all-oral, highly efficacious, simple, and ll-tolerated regimen
C-WORTHy: MK-5172/MK-8742 ± RBV in 471 HCV G1-infected patients
Treatment-naive, non-cirrhotic12 weeks ± RBV
(n = 65)
atment-naive on-cirrhotic
2 weeks ± RBV(n = 94)
Treatment-naive Cirrhotic
12-18 weeks ± RBV(n = 123)
HIV/HCV co-infectedNon-cirrhotic
12 weeks ± RBV(n = 59)
Null responders Cirrhotic / Non-cirrhotic
12-18 weeks ± RBV(n = 130)
owski, et al., Clin Infect Dis. 30 (Suppl 1):S77, 2000; 2. Rockstroh JK, et al., Am J Gastroenterol. 91:2563, 1996; HS Antiretroviral Guidelines; for Adults and Adolescents. February, 2013; 4. Naggie S, et al. Gastroenterology. 24, 2012
MK-5172 + MK-8742 + RBV
MK-5172 + MK-8742 (No RBV)
= 29
= 30
Follow-up
Follow-up
D1 TW12 SVR12TW4TW2 TW8 SVR24SVR4
Primary endpoint
72 (100 mg QD) + MK-8742 (50 mg QD); 12 weeks
100 100 100 9710090 90 90
0102030405060708090
100
TW4 TW8 TW12 SVR4Week
MK-5172 +MK-8742 +RBV (n=29)
MK-5172 +MK-8742(No RBV;n=30)29
2928 29
2929
2929
3030
2629*
2730
2730
logic Failures: 1 relapse in +RBV arm; 2 breakthrough and 1 lost to follow up in No RBV arm
ne patient has not yet reached FU4
cacyTreatment with MK-5172 + MK-8742 ± RBV for 12 weeks demonstrated high efficacy (90-97% 4 weeks after end-of-treatment; SVR4)Three of 59 patients experienced virologic failure
– 1 relapse, 2 breakthrough
etyMK-5172 + MK-8742 ± RBV was generally safe and well tolerated in co-infected patientsThe most common AEs in co-infected patients were headache and astheniaAll co-infected patients had suppressed HIV and stable CD4 countsThere were no early discontinuations due to drug-related adverse events
erallObserved efficacy and safety in patients with HIV/HCV coinfection was similar to other patient populations in C-WORTHy
