High Efficacy in Patients With Chronic Hepatitis C Virus · 2016. 11. 20. · Gastroenterology....
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Results Demographics and Characteristics • Patients from 30 countries were enrolled ( Figure 2 and Table 1 ) – 508 patients (47.5%) from Asian countries • Japan was the most heavily represented country, contributing 26.9% of all enrolled patients – 359 patients (34%) from European countries – 180 patients (17%) from the American continent – 23 patients (2%) from Australasia Figure 2. Geographic distribution of enrolled patients Romania 25 (2.3%) Greece 3 (0.3%) Estonia 1 (0.1%) Lithuania 23 (2.2%) Poland 19 (1.8%) Sweden 6 (0.6%) Norway 4 (0.4%) Denmark 6 (0.6%) Netherlands 2 (0.2%) United Kingdom 7 (0.7%) Germany 21 (2.0%) Spain 30 (2.8%) France 38 (3.6%) Czech Republic 39 (3.6%) Israel 63 (5.9%) Turkey 13 (1.2%) Hungary 19 (1.8%) Italy 17 (1.6%) Russian Federation 86 (8.0%) Canada 9 (0.8%) United States 170 (15.9%) Thailand 3 (0.3%) South Korea 74 (6.9%) New Zealand 2 (0.2%) Malaysia 1 (0.1%) Vietnam 4 (0.4%) Taiwan 75 (7.0%) Japan 288 (26.9%) Australia 21 (2.0%) Argentina 1 (0.1%) Table 1. Patient demographics All patients (N = 1070) Female, n (%) 534 (49.9) Race, n (%) Asian 462 (43.2) Black/African American 95 (8.9) White 504 (47.1) Other/missing 9 (0.8) Age, years, mean (SD) 53.7 (13.0) Treatment history, n (%) Naive 851 (79.5) Experienced 219 (20.5) Baseline viral load, n (%) ≤800,000 IU/mL 342 (32.0) >800,000 IU/mL 728 (68.0) HIV co-infection, n (%) 54 (5.1) Cirrhotic, n (%) 189 (17.7) SD, standard deviation. Presented at The Liver Meeting 2016 ® ; November 11-15, 2016; Boston, MA, USA High Efficacy in Patients With Chronic Hepatitis C Virus (HCV) Genotype 1b Infection Treated with Elbasvir/ Grazoprevir for 12 Weeks: An Integrated Analysis Zeuzem S 1 ; Serfaty L 2 ; Vierling JM 3 ; Cheng W 4 ; George J 5 ; Sperl J 6 ; Strasser S 7 ; Kumada H 8 ; Hwang P 9 ; Robertson M 9 ; Wahl J 9 ; Barr E 9 ; Talwani R 9 ; Platt H 9 1 Goethe University Hospital, Frankfurt, Germany; 2 Université Pierre & Marie Curie, Paris, France; 3 Baylor College of Medicine, Baylor-St. Luke’s Medical Center, Houston, TX, USA; 4 Royal Perth Hospital, Perth, WA, Australia; 5 University of Sydney, Sydney, NSW, Australia; 6 Institut Klinické a Experimentální Medicíny (IKEM), Prague, Czech Republic; 7 AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 8 Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 9 Merck & Co., Inc., Kenilworth, NJ, USA. Background • Genotype (GT)1b is the most common subtype of hepatitis C virus (HCV) infection, responsible for 22% of all infections worldwide 1 – Significant regional variability • 26% of cases in North America • 39% of cases in Latin America • 50% of cases in Europe – Common in many countries throughout Asia • 65% of infections in Japan • 45% of infections in Taiwan and South Korea • Elbasvir (EBR) is a once-daily NS5A inhibitor and grazoprevir (GZR) is a once-daily HCV NS3/4A protease inhibitor ( Figure 1 ) – Approved in Europe, the United States, Canada, and other countries worldwide 2 – Broad activity vs most HCV genotypes in vitro 3-5 – Efficacious in treatment-naive and treatment-experienced patients, cirrhotic and noncirrhotic patients, HIV/HCV co-infected patients, and those with chronic kidney disease 6-9 Figure 1. EBR/GZR • HCV NS5A inhibitor, 50 mg Elbasvir (MK-8742) Grazoprevir (MK-5172) • HCV NS3/4A inhibitor, 100 mg • Initial phase 2 study demonstrated – 100% (13/13) of GT1b-infected patients treated for 12 weeks achieved SVR12 10 – 93.5% (29/31) of GT1b-infected patients treated for 8 weeks achieved SVR12 11 • Subsequently, phase 2/3 studies demonstrated an SVR12 of 96.5% (246/255) in GT1b-infected patients treated for 12 weeks – Excluding 7 patients with nonvirologic failure, 99.2% (246/248) achieved SVR12 – Virologic failure (relapse) occurred in 0.8% (2/255) of patients Aim • To perform an integrated analysis of 1070 patients with HCV GT1b infection from 30 countries who received EBR/GZR for 12 weeks in 11 phase 2/3 international clinical trials Patients and Methods Study Design • Retrospective integrated post hoc analysis of data from 11 clinical trials in the EBR/GZR phase 2/3 clinical development program, using a pooled dataset of 1070 patients who received EBR/GZR (50 mg/100 mg) for 12 weeks • Patients were treatment-naive or treatment-experienced, and included those with compensated cirrhosis or HIV co- infection – Patients with decompensated liver disease or evidence of hepatocellular carcinoma were excluded • The primary endpoint of all 11 studies was SVR12 (HCV RNA <15 IU/mL in phase 3 studies and <25 IU/mL in phase 2 studies) – Full analysis set (FAS): includes all patients who received ≥1 dose of study medication – Modified FAS (mFAS): excludes patients with nonvirologic failure • Population sequencing was performed at baseline and at the time of virologic failure. – The specific NS5A loci evaluated were any polymorphism at amino acid positions 28, 30, 31, and 93 Virologic Response • In the FAS population, 97.2% (1040/1070) of patients with HCV GT1b infection receiving EBR/GZR for 12 weeks achieved SVR12 ( Figure 3 ) – SVR12 in the mFAS population was 98.6% (1040/1055) Figure 3. SVR12 97.2 98.6 0 25 50 75 100 FAS mFAS 1040 1070 1040 1055 SVR12, % 15 15 Virologic failure: relapse Nonvirologic failure 15 0 FAS includes all patients who received ≥1 dose of study medication. mFAS excludes 15 patients who discontinued for reasons unrelated to study medication. • Subgroup analyses are shown in Figure 4 Figure 4. SVR12 subgroup analyses (FAS) 100 60 70 80 90 97.2 (96.0, 98.1) 97.2 (95.4, 98.4) 97.2 (95.4, 98.4) 97.2 (95.4, 98.5) 97.6 (95.8, 98.8) 94.7 (88.1, 98.3) 100.0 (63.1, 100.0) 99.0 (94.9, 100.0) 97.1 (94.6, 98.7) 97.9 (96.0, 99.0) 95.3 (91.7, 97.6) 97.3 (96.0, 98.3) 96.8 (93.5, 98.7) 98.0 (95.8, 99.2) 96.8 (95.3, 98.0) 94.4 (84.6, 98.8) 97.3 (96.2, 98.2) 99.5 (97.1, 100.0) 96.7 (95.3, 97.8) 1040/1070 519/534 521/536 490/504 451/462 90/95 8/8 105/106 302/311 411/420 222/233 828/851 212/219 335/342 705/728 51/54 989/1016 188/189 852/881 ALL Sex Male Female Race White Asian Black/AA Other Age 18-35 36-50 51-64 ≥65 Treatment history Naive Experienced Baseline viral load ≤800,000 IU/mL >800,000 IU/mL HIV Co-infection Yes No Cirrhosis Yes No AA, African American; CI, confidence interval. • NS5A resistance-associated variants (RAVs) at amino acid positions 28, 30, 31, and 93 were detected in 21.6% (227/1050) of patients at baseline (Figure 5A) – SVR12 was 94.7% (215/227) and 99.6% (820/823) in patients with and without baseline NS5A RAVs, respectively • Polymorphisms at amino acid Y93 were present at baseline in 9.9% (104/1050) of patients ( Figure 5B ) – Of the 104 patients with Y93 polymorphisms at baseline, only 3 did not have a Y93H variant (Y93C/Y, n = 1; Y93S, n = 2). – SVR12 was 95.2% (99/104) in patients with polymorphisms at Y93 • All 5 patients with a Y93 polymorphism at baseline who subsequently had virologic failure had the Y93H variant Figure 5. Prevalence and impact on SVR12 of baseline NS5A RAVs at (A) positions 28, 30, 31, and 93 and (B) at position 93 only in patients with HCV GT1b infection † 0 25 50 75 100 NS5A RAVs Absent SVR12, % 820 823 No RAVS n = 823 (78%) RAVS n = 227 (22%) Prevalence of NS5A RAVS † A B 99.6 94.7 No Y93 RAVS n = 946 (90%) Y93 RAVS n = 104 (10%) Prevalence of NS5A RAVS at position Y93 † 98.9 95.2 215 227 NS5A RAVs Present 0 25 50 75 100 Y93 RAVs Absent SVR12, % Y93 RAVs Present 936 946 99 104 0 25 50 75 100 SVR12, % 0 25 50 75 100 SVR12, % † Resistance analysis population includes 1050 patients with HCV GT1b infection, baseline sequencing available, and a treatment outcome of either SVR12 or virologic failure. Safety • A 12-week regimen of EBR/GZR was well tolerated, with a favorable safety profile in patients with HCV GT1b infection included in this analysis • Serious adverse events (SAEs) occurred in 3.3% (35/1070) of patients, comparable to the rate of 2.9% (3/105) observed in placebo controls • Specifically, late elevations of alanine aminotransferase (ALT)/aspartate aminotransferase (AST) (elevation of ALT or AST >5× upper limit of normal on or after treatment week 4 after normalization on treatment), were rare and observed in 1.1% of GT1b-infected patients, which was comparable to the rate of 0.8% in the overall population of patients treated with EBR/GZR for 12 weeks Conclusions • This integrated analysis of 1070 patients demonstrated EBR/GZR for 12 weeks was highly efficacious in patients with HCV GT1b infection. • The overall SVR12 was 97.2% (FAS population) – SVR12 was 98.6% in the mFAS population, which excluded patients with nonvirologic failure – SVR12 rates were high regardless of race, age, treatment history, baseline viral load, presence of cirrhosis, HIV co-infection, or presence of baseline NS5A RAVs • EBR/GZR demonstrated a favorable safety profile – The rates of SAEs were comparable between those treated with EBR/GZR or placebo – Late ALT/AST elevations were detected in 1.1% of patients, comparable to the rate in the overall population of all patients treated with EBR/GZR for 12 weeks • Further investigation of shorter duration regimens for GT1b-infected patients is warranted – SVR12 rates of 93.5% (29/31) were achieved in noncirrhotic patients with GT1b infection receiving EBR/GZR for 8 weeks – An 8-week treatment duration for EBR/GZR is approved in Canada for treatment-naive, noncirrhotic GT1b-infected patients 874 References 1. Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol . 2014;61(1 suppl):S45-S57. 2. Zepatier [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2016. 3. Summa V, Ludmerer SW, McCauley JA, et al. MK-5172, a selective inhibitor of hepatitis C virus NS3/4a protease with broad activity across genotypes and resistant variants. Antimicrob Agents Chemother . 2012;56:4161-4167. 4. Harper S, McCauley JA, Rudd MT, et al. Discovery of MK-5172, a macrocyclic hepatitis C virus NS3/4a protease inhibitor. ACS Med Chem Lett . 2012;3:332-336. 5. Coburn CA, Meinke PT, Chang W, et al. Discovery of MK-8742: an HCV NS5A inhibitor with broad genotype activity. ChemMedChem. 2013;8:1930-1940. 6. Kwo P, Gane E, Peng C-Y, et al. Effectiveness of elbasvir and grazoprevir combination, with or without ribavirin, for treatment-experienced patients with chronic hepatitis C infection. Gastroenterology . 2016. doi: 10.1053/j.gastro.2016.09.045. 7. Roth D, Nelson DR, Bruchfeld A, et al. Grazoprevir plus elbasvir in treatment-naive and treatment-experienced patients with hepatitis C virus genotype 1 infection and stage 4-5 chronic kidney disease (the C-SURFER study): a combination phase 3 study. Lancet . 2015;386:1537-1545. 8. Rockstroh JK, Nelson M, Katlama C, et al. Efficacy and safety of grazoprevir (MK-5172) and elbasvir (MK-8742) in patients with hepatitis C virus and HIV co-infection (C-EDGE CO-INFECTION): a non-randomised, open-label trial. Lancet HIV . 2015;2:e319-e327. 9. Zeuzem S, Ghalib R, Reddy KR, et al. Grazoprevir-elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis C virus genotype 1, 4, or 6 infection: a randomized trial. Ann Intern Med . 2015;163:1-13. 10. Sulkowski M, Hezode C, Gerstoft J, et al. Efficacy and safety of 8 weeks versus 12 weeks of treatment with grazoprevir (MK-5172) and elbasvir (MK-8742) with or without ribavirin in patients with hepatitis C virus genotype 1 mono-infection and HIV/hepatitis C virus co-infection (C-WORTHY): a randomised, open-label phase 2 trial. Lancet . 2015;385:1087-1097. 11. Vierling JM, Kugelmas M, Lawitz E, et al, Efficacy of an eight-week regimen of grazoprevir plus elbasvir with and without ribavirin in treatment-naive, noncirrhotic HCV genotype 1B infection. Presented at: The Liver Meeting ® 2015, November 13-17, 2015, San Francisco, CA, USA. Acknowledgments • We extend our gratitude to the patients, their families, investigators, and site personnel who participated in this study • Medical writing assistance was provided by Tim Ibbotson, PhD, of ApotheCom (Yardley, PA, USA) and funded by Merck & Co., Inc. • The studies included in this integrated analysis were funded by Merck & Co., Inc., Kenilworth, NJ, USA Copyright © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. All rights reserved.
Transcript of High Efficacy in Patients With Chronic Hepatitis C Virus · 2016. 11. 20. · Gastroenterology....
ResultsDemographics and Characteristics • Patients from 30 countries were enrolled (Figure 2 and Table 1)
– 508 patients (47.5%) from Asian countries• Japan was the most heavily represented country, contributing 26.9% of all enrolled patients
– 359 patients (34%) from European countries – 180 patients (17%) from the American continent – 23 patients (2%) from Australasia
Figure 2. Geographic distribution of enrolled patients
Romania
25 (2.3%)Greece
3 (0.3%)
Estonia
1 (0.1%)
Lithuania
23 (2.2%)
Poland
19 (1.8%)
Sweden
6 (0.6%)
Norway
4 (0.4%)
Denmark
6 (0.6%)
Netherlands
2 (0.2%)
United Kingdom
7 (0.7%)
Germany
21 (2.0%)
Spain
30 (2.8%)
France
38 (3.6%)
Czech Republic
39 (3.6%)
Israel
63 (5.9%)
Turkey
13 (1.2%)
Hungary
19 (1.8%)Italy
17 (1.6%)
New Zealand
2 (0.2%)
Australia
21 (2.0%)
Canada
9 (0.8%)
United States
170 (15.9%)
Argentina
1 (0.1%)
Russian Federation
86 (8.0%)
Canada
9 (0.8%)
United States
170 (15.9%)
Argentina
1 (0.1%)
Thailand
3 (0.3%)
South Korea
74 (6.9%)
New Zealand
2 (0.2%)
Malaysia
1 (0.1%)
Vietnam
4 (0.4%)
Taiwan
75 (7.0%)
Japan
288 (26.9%)
Australia
21 (2.0%)
Canada
9 (0.8%)
United States
170 (15.9%)
Argentina
1 (0.1%)
Table 1. Patient demographics All patients
(N = 1070)
Female, n (%) 534 (49.9)
Race, n (%)
Asian 462 (43.2)
Black/African American 95 (8.9)
White 504 (47.1)
Other/missing 9 (0.8)
Age, years, mean (SD) 53.7 (13.0)
Treatment history, n (%)
Naive 851 (79.5)
Experienced 219 (20.5)
Baseline viral load, n (%)
≤800,000IU/mL 342 (32.0)
>800,000IU/mL 728 (68.0)
HIVco-infection,n(%) 54 (5.1)
Cirrhotic, n (%) 189 (17.7) SD, standard deviation.
Presented at The Liver Meeting 2016®; November 11-15, 2016; Boston, MA, USA
High Efficacy in Patients With Chronic Hepatitis C Virus (HCV) Genotype 1b Infection Treated with Elbasvir/Grazoprevir for 12 Weeks: An Integrated Analysis
Zeuzem S1;SerfatyL2;VierlingJM3; Cheng W4; George J5; Sperl J6; Strasser S7; Kumada H8; Hwang P9;RobertsonM9; Wahl J9; Barr E9; Talwani R9; Platt H9
1GoetheUniversityHospital,Frankfurt,Germany;2UniversitéPierre&MarieCurie,Paris, France; 3BaylorCollegeofMedicine,Baylor-St.Luke’sMedicalCenter,Houston,TX,USA;4Royal Perth Hospital, Perth, WA, Australia; 5UniversityofSydney, Sydney, NSW, Australia; 6InstitutKlinickéaExperimentálníMedicíny(IKEM),Prague, Czech Republic; 7AWMorrowGastroenterologyandLiverCentre, Royal Prince Alfred Hospital, Sydney, NSW, Australia; 8Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 9Merck&Co.,Inc.,Kenilworth,NJ,USA.
Background • Genotype (GT)1b is the most common subtype of hepatitis Cvirus(HCV)infection,responsiblefor22%ofallinfectionsworldwide1
– Significantregionalvariability• 26% of cases in North America• 39%ofcasesinLatinAmerica• 50% of cases in Europe
– Common in many countries throughout Asia• 65% of infections in Japan• 45% of infections in Taiwan and South Korea
• Elbasvir(EBR)isaonce-dailyNS5Ainhibitorandgrazoprevir(GZR)isaonce-dailyHCVNS3/4Aproteaseinhibitor(Figure 1)
– ApprovedinEurope,theUnitedStates,Canada,andothercountries worldwide2
– BroadactivityvsmostHCVgenotypesinvitro3-5
– Efficaciousintreatment-naiveandtreatment-experiencedpatients,cirrhoticandnoncirrhoticpatients,HIV/HCV co-infectedpatients,andthosewithchronickidneydisease6-9
Figure 1. EBR/GZR
• HCV NS5A inhibitor,
50 mg
Elbasvir
(MK-8742)
Grazoprevir
(MK-5172)
• HCV NS3/4A inhibitor,
100 mg
• Initialphase2studydemonstrated – 100%(13/13)ofGT1b-infectedpatientstreatedfor12weeksachievedSVR1210
– 93.5%(29/31)ofGT1b-infectedpatientstreatedfor8weeksachievedSVR1211
• Subsequently,phase2/3studiesdemonstratedanSVR12of96.5%(246/255)inGT1b-infectedpatientstreatedfor12weeks
– Excluding 7 patients with nonvirologic failure, 99.2% (246/248)achievedSVR12
– Virologicfailure(relapse)occurredin0.8%(2/255)ofpatients
Aim • Toperformanintegratedanalysisof1070patientswithHCVGT1b infection from 30 countries who received EBR/GZR for 12 weeks in 11 phase 2/3 international clinical trials
Patients and MethodsStudy Design • Retrospective integrated post hoc analysis of data from 11 clinical trials in the EBR/GZR phase 2/3 clinical development program, using a pooled dataset of 1070 patients who received EBR/GZR (50 mg/100 mg) for 12 weeks
• Patientsweretreatment-naiveortreatment-experienced, andincludedthosewithcompensatedcirrhosisorHIVco-infection
– Patients with decompensated liver disease or evidence of hepatocellular carcinoma were excluded
• Theprimaryendpointofall11studieswasSVR12(HCVRNA <15IU/mLinphase3studiesand<25IU/mLinphase2studies)
– Full analysis set (FAS): includes all patients who received ≥1doseofstudymedication
– ModifiedFAS(mFAS):excludespatientswithnonvirologicfailure
• Population sequencing was performed at baseline and at the time of virologic failure.
– ThespecificNS5Alocievaluatedwereanypolymorphismat amino acid positions 28, 30, 31, and 93
Virologic Response • IntheFASpopulation,97.2%(1040/1070)ofpatientswithHCVGT1binfectionreceivingEBR/GZRfor12weeksachievedSVR12(Figure 3)
– SVR12inthemFASpopulationwas98.6%(1040/1055)
Figure 3. SVR1297.2 98.6
0
25
50
75
100
FAS mFAS
10401070
10401055
SVR
12, %
1515
Virologic failure: relapseNonvirologic failure
150
FASincludesallpatientswhoreceived≥1doseofstudymedication.mFASexcludes15patientswhodiscontinuedforreasonsunrelatedtostudymedication.
• Subgroup analyses are shown in Figure 4
Figure 4. SVR12 subgroup analyses (FAS)
10060 70 80 90
97.2 (96.0, 98.1)
97.2 (95.4, 98.4)
97.2 (95.4, 98.4)
97.2 (95.4, 98.5)
97.6 (95.8, 98.8)
94.7 (88.1, 98.3)
100.0 (63.1, 100.0)
99.0 (94.9, 100.0)
97.1 (94.6, 98.7)
97.9 (96.0, 99.0)
95.3 (91.7, 97.6)
97.3 (96.0, 98.3)
96.8 (93.5, 98.7)
98.0 (95.8, 99.2)
96.8 (95.3, 98.0)
94.4 (84.6, 98.8)
97.3 (96.2, 98.2)
99.5 (97.1, 100.0)
96.7 (95.3, 97.8)
1040/1070
519/534
521/536
490/504
451/462
90/95
8/8
105/106
302/311
411/420
222/233
828/851
212/219
335/342
705/728
51/54
989/1016
188/189
852/881
ALL
Sex
Male
Female
Race
White
Asian
Black/AA
Other
Age
18-35
36-50
51-64
≥65
Treatment history
Naive
Experienced
Baseline viral load
≤800,000 IU/mL
>800,000 IU/mL
HIV Co-infection
Yes
No
Cirrhosis
Yes
No
AA,AfricanAmerican;CI,confidenceinterval.
• NS5Aresistance-associatedvariants(RAVs)ataminoacidpositions28,30,31,and93weredetectedin21.6%(227/1050) of patients at baseline (Figure 5A)
– SVR12was94.7%(215/227)and99.6%(820/823)inpatientswithandwithoutbaselineNS5ARAVs,respectively
• Polymorphisms at amino acid Y93 were present at baseline in 9.9% (104/1050) of patients (Figure 5B) – Of the 104 patients with Y93 polymorphisms at baseline, only 3 did not have a Y93H variant (Y93C/Y, n = 1; Y93S, n = 2).
– SVR12was95.2%(99/104)inpatientswithpolymorphismsatY93• All 5 patients with a Y93 polymorphism at baseline who subsequently had virologic failure had the Y93H variant
Figure 5. Prevalence and impact on SVR12 of baseline NS5A RAVs at (A) positions 28, 30, 31, and 93 and (B) at position 93 only in patients with HCV GT1b infection†
0
25
50
75
100
NS5A RAVs Absent
SVR
12, %
820823
No RAVSn = 823 (78%)
RAVSn = 227 (22%)
Prevalence of NS5A RAVS†A
B
99.6 94.7
NS5A Y93 RAVs PresentNS5A Y93 RAVs Absent
No Y93 RAVSn = 946(90%)
Y93 RAVSn = 104(10%)
Prevalence of NS5A RAVSat position Y93†
98.9 95.2
215227
NS5A RAVs Present
0
25
50
75
100
Y93 RAVs Absent
SVR
12, %
Y93 RAVs Present
936946
99104
0
25
50
75
100
SVR
12, %
0
25
50
75
100
SVR
12, %
†Resistanceanalysispopulationincludes1050patientswithHCVGT1binfection,baselinesequencingavailable,andatreatmentoutcomeofeitherSVR12orvirologicfailure.
Safety • A12-weekregimenofEBR/GZRwaswelltolerated,withafavorablesafetyprofileinpatientswithHCVGT1binfection included in this analysis
• Serious adverse events (SAEs) occurred in 3.3% (35/1070) of patients, comparable to the rate of 2.9% (3/105) observed in placebo controls
• Specifically,lateelevationsofalanineaminotransferase(ALT)/aspartateaminotransferase(AST)(elevationofALTor AST >5× upper limit of normal on or after treatment week 4 after normalization on treatment), were rare and observedin1.1%ofGT1b-infectedpatients,whichwascomparabletotherateof0.8%intheoverallpopulation of patients treated with EBR/GZR for 12 weeks
Conclusions • Thisintegratedanalysisof1070patientsdemonstratedEBR/GZRfor12weekswashighlyefficaciousinpatientswithHCVGT1binfection.
• TheoverallSVR12was97.2%(FASpopulation) – SVR12was98.6%inthemFASpopulation,whichexcludedpatientswithnonvirologicfailure – SVR12rateswerehighregardlessofrace,age,treatmenthistory,baselineviralload,presenceofcirrhosis,HIVco-infection,orpresenceofbaselineNS5ARAVs
• EBR/GZRdemonstratedafavorablesafetyprofile – The rates of SAEs were comparable between those treated with EBR/GZR or placebo – LateALT/ASTelevationsweredetectedin1.1%ofpatients,comparabletotherateintheoverallpopulation of all patients treated with EBR/GZR for 12 weeks
• FurtherinvestigationofshorterdurationregimensforGT1b-infectedpatientsiswarranted – SVR12ratesof93.5%(29/31)wereachievedinnoncirrhoticpatientswithGT1binfectionreceivingEBR/GZRfor 8 weeks
– An8-weektreatmentdurationforEBR/GZRisapprovedinCanadafortreatment-naive,noncirrhoticGT1b-infectedpatients
874
References1. Gower E, Estes C, Blach S, et al. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol.2014;61(1suppl):S45-S57.2. Zepatier[packageinsert].WhitehouseStation,NJ:MerckSharp&DohmeCorp.;2016.3. SummaV,LudmererSW,McCauleyJA,etal.MK-5172,aselectiveinhibitorofhepatitisCvirusNS3/4aproteasewithbroadactivityacrossgenotypesand
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Acknowledgments • We extend our gratitude to the patients, their families, investigators, and site personnel who participated in this study • MedicalwritingassistancewasprovidedbyTimIbbotson,PhD,ofApotheCom(Yardley,PA,USA)andfundedbyMerck&Co.,Inc. • ThestudiesincludedinthisintegratedanalysiswerefundedbyMerck&Co.,Inc.,Kenilworth,NJ,USA
Copyright©2016MerckSharp&DohmeCorp.,asubsidiaryofMerck&Co.,Inc.Allrightsreserved.
