Genotype 1 HCV in 2016: Clinical Decision Making in a Time of Plenty Ira M. Jacobson, MD Chair, Department of Medicine Mount Sinai Beth Israel Senior Faculty and Vice-Chair, Department of Medicine Icahn School of Medicine at Mount Sinai New York, New York Supported by educational grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck, and ViiV Healthcare.
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Disclosures Ira. M. Jacobson, MD, has disclosed that he has received funds for research support from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen, and Merck; has served on speaker bureaus for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Janssen; and has received consulting fees from AbbVie, Bristol- Myers Squibb, Gilead Sciences, Intercept, Janssen, Merck, and Trek.
New Regimens and Data for Genotype 1 HCV Infection AASLD Guidance Updated July 6, 2016 AASLD guidance stratifies regimens as “recommended” and “alternative” AASLD, American Association for the Study of Liver Diseases; HCV, hepatitis C virus. Slide credit: clinicaloptions.com AASLD/IDSA. HCV guidelines. April 2016.
AASLD: Recommended and Alternative Regimens for GT1 Without Cirrhosis Nucleotide No nucleotide Population LDV/SOF DCV + SOF SMV + SOF SOF/VEL GZR/EBR OBV/PTV/RTV + DSV GT1a 12 wks 16 wks + RBV† 12 wks + RBV GT1b AASLD, American Association for the Study of Liver Diseases; DCV, daclatasvir; DSV, dasabuvir; EBR, elbasvir; GT, genotype; GZR, grazoprevir; LDV, ledipasvir; OBV, ombitasvir; PTV, paritaprevir; RAV, resistance associated variant; RBV, ribavirin; RTV, ritonavir; SMV, simeprevir; SOF, sofosbuvir; VEL, velpatasvir. †If NS5A RAVs present. Recommended Alternative Slide credit: clinicaloptions.com AASLD/IDSA. HCV guidelines. July 2016.
AASLD: Recommended and Alternative Regimens for GT1 With Compensated Cirrhosis Nucleotide No nucleotide Population LDV/SOF DCV + SOF SMV + SOF SOF/VEL GZR/EBR OBV/PTV/RTV + DSV GT1a Naive PR exp 12 wks 12 wks + RBV or 24 wks 24 wks ± RBV 24 wks ± RBV* 16 wks + RBV† 12 wks 16 wks + RBV† 24 wks + RBV GT1b + RBV RBV AASLD, American Association for the Study of Liver Diseases; DCV, daclatasvir; DSV, dasabuvir; EBR, elbasvir; GT, genotype; GZR, grazoprevir; LDV, ledipasvir; OBV, ombitasvir; PR, peginterferon/ribavirin; PTV, paritaprevir; RAV, resistance associated variant; RBV, ribavirin; RTV, ritonavir; SMV, simeprevir; SOF, sofosbuvir; VEL, velpatasvir. *Not with Q80K. †If NS5A RAVs present. Recommended Alternative Slide credit: clinicaloptions.com AASLD/IDSA. HCV guidelines. July 2016.
Sofosbuvir/Velpatasvir: Approved June 2016 Genotype 1a or 1b, without cirrhosis or with compensated cirrhosis (Child-Pugh A), treatment naive or treatment experienced 12 weeks sofosbuvir/velpatasvir Genotype 1a or 1b, with decompensated cirrhosis (Child-Pugh B or C), treatment naive or treatment experienced 12 weeks sofosbuvir/velpatasvir + ribavirin Slide credit: clinicaloptions.com Sofosbuvir/velpatasvir prescribing information.
ASTRAL-1: VEL/SOF FDC for 12 Wks in GT1/2/4/5/6 With and Without Cirrhosis Velpatasvir (GS-5816): pangenotypic HCV NS5A inhibitor GT3 pts evaluated in separate study 19% cirrhosis, 32% treatment experienced 99 99 100 98 75 SVR12* (%) FDC, fixed-dose combination; GT, genotype; HCV, hepatitis C virus; SOF, sofosbuvir; VEL, velpatasvir. 50 25 n/N = 618/624 206/210 117/118 Overall GT1a GT1b *HCV RNA < 15 IU/mL Slide credit: clinicaloptions.com Feld JJ, et al. AASLD 2015. Abstract LB-2.
ASTRAL-4: VEL/SOF FDC for HCV in Pts With Decompensated Liver Disease Treatment-naive or treatment-experienced pts with GT1-6 HCV infection and CTP B cirrhosis (N = 267) 55% treatment experienced; 95% MELD < 15; 75% to 83% ascites; 58% to 66% encephalopathy GT1: 78%; GT3: 15%, GT2/4/6: 8% Wk 0 Wk 12 Wk 24 Wk 36 SVR12 VEL/SOF* n = 90 CTP, Child-Turcotte-Pugh; FDC, fixed-dose combination; GT, genotype; HCV, hepatitis C virus; MELD, Model for End-Stage Liver Disease; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir. SVR12 n = 87 VEL/SOF* + RBV SVR12 n = 90 VEL/SOF* *100 mg/400mg Slide credit: clinicaloptions.com Charlton MR, et al. AASLD 2015. Abstract LB-13.
ASTRAL-4: VEL/SOF FDC for HCV in Pts With Decompensated Liver Disease SOF/VEL 12 wks SOF/VEL + RBV 12 wks SOF/VEL 24 wks 94 96 100 92 86 88 83 80 60 SVR12 (%) 40 20 n/N = 75/90 82/87 77/90 60/68 65/68 65/71 Overall Genotype 1 Breakthrough, n Relapse, n LTFU, n Death, n - 11 1 3 1 2 - 1 7 3 2 - 5 1 2 - 1 2 - 3 AE, adverse event; D/c, discontinued; FDC, fixed-dose combination; HA, headache; Hb, hemoglobin; HCV, hepatitis C virus; LTFU, lost to follow-up; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir. D/c due to AE: 3% (n = 9) Death due to AE: 3% (n = 9) Fatigue (29%); nausea (23%); HA (22%); anemia (13%; 31% in RBV arm) AE more frequent with RBV RBV arm: Hb < 10 mg/dL, 23%; Hb < 8.5 mg/dL, 7% RBV decreased in 37% and d/c in 17% Slide credit: clinicaloptions.com Charlton MR, et al. AASLD 2015. Abstract LB-13
ASTRAL-5: VEL/SOF FDC for 12 Wks in Pts Coinfected With HCV and HIV-1 SVR12 N = 106 VEL/SOF Wk 12 24 100 100 100 95 95 92 92 80 2 relapse 1 LTFU 1 withdrew consent 60 1 LTFU SVR12 (%) FDC, fixed-dose combination; GT, genotype; HCV, hepatitis C virus; LTFU, lost to follow-up; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir. 40 20 99/ 104 62/ 65 11/ 12 11/ 11 11/ 12 4/ 4 n/N = Total GT1a GT1b GT2 GT3 GT4 Slide credit: clinicaloptions.com Wyles D, et al. EASL 2016. Abstract PS104.
Grazoprevir/Elbasvir: Approved Jan 2016 Genotype 1a, with/without compensated cirrhosis, treatment naive or treatment experienced Without NS5A RAVs: GZR/EBR, 12 wks With NS5A RAVs: GZR/EBR + RBV, 16 wks* RAVs at positions 28, 30, 31, 93 Genotype 1b, with/without compensated cirrhosis, treatment naive or treatment experienced GZR/EBR, 12 wks RAV testing not indicated EBR, elbasvir; GZR, grazoprevir; RAV, resistance associated variant. *Listed as “alternative” regimen. Slide credit: clinicaloptions.com AASLD/IDSA. HCV guidelines. April 2016.
C-EDGE TN: 12 Wks of GZR/EBR in Genotype 1, 4, or 6 100 100 95 97 99 94 92 80 80 60 SVR12 (%) 40 299/ 316 231/ 246 68/ 70 144/ 157 129/ 131 18/ 18 8/ 10 20 n/N = All Pts Noncirrhotics Cirrhotics GT1a GT1b 3 1 9 GT4 1 GT6 2 Non-VF Breakthrough Relapse Good safety and tolerability profile No drug-related serious AEs; 2 deaths unrelated to drug No concurrent ALT/bilirubin increase Lower SVR12 rates in pts with BL NS5A RAVs (2/9, 22%); associated with > 5-fold loss of EBR susceptibility Virologic failure only if baseline HCV RNA > 800,000 IU/mL AE, adverse event; ALT, alanine aminotransferase; BL, baseline; EBR, elbasvir; GT, genotype; GZR, grazoprevir; RAV, resistance associated variant; SVR, sustained virologic response; VF, virologic failure. Slide credit: clinicaloptions.com Zeuzem S, et al. Ann Intern Med. 2015;163:1-13.
C-EDGE TE: 12 or 16 Wks of GZR/EBR ± RBV in Treatment-Experienced GT1, 4, or 6 92 94 97 100 80 60 40 20 92 12 wks SVR12 (%, 95% CI) 16 wks 97/ 105 98/ 104 97/ 105 103/ 106 n/N = No RBV + RBV No RBV + RBV Breakthrough Rebound Relapse LTFU/early d/c 6 2 0060 1241 0003 *ITT population. AASLD, American Association for the Study of Liver Diseases; d/c, discontinued; EBR, elbasvir; GT, genotype; GZR, grazoprevir; ITT, intent to treat; LTFU, lost to follow-up; RAV, resistance associated variant; RBV, ribavirin; SVR, sustained virologic response. Virologic failures driven by RAVs Analysis from AASLD 2015 shows that presence of baseline NS5A RAVs by population sequencing or next-generation sequencing (with 10% to 20% cutoff) is predictive of failure Kwo P, et al. EASL 2015. Abstract P0886. Jacobson I, et al. AASLD 2015. Abstract LB22. Slide credit: clinicaloptions.com
C-EDGE TE: Efficacy of 12 Wks of GZR/EBR ± RBV by Baseline RAVs SVR12, n/N (%) Total NS3 Variants Not Detectable NS3 RAVs ≤ 5-Fold Shift > 5-Fold Shift GT1a 95% 107/112 (96) 104/111 (94) GT1b 99% 133/135 (99) 9/9 (100) 1/1 (100%) NS5A Variants Not Detectable NS5A RAVs 190/192 (99) 10/10 (100) 11/21 (52) 127/127 (100) 16/18 (89) EBR, elbasvir; GT, genotype; GZR, grazoprevir; RAV, resistance associated variant; RBV, ribavirin; SVR, sustained virologic response. Should baseline RAV testing be done with this regimen? The NS5A RAVs that matter are in the 28, 30, 31, and 93 positions Slide credit: clinicaloptions.com Kwo P, et al. EASL 2015. Abstract P0886.
C-SURFER: Grazoprevir/Elbasvir in Pts With GT1 HCV and Stage 4/5 CKD Treatment Wk 12 Follow-up Wk 4 Follow-up Wk 16 SVR12* Randomized period GT1 HCV–infected pts with stage 4/5 CKD (n = 224) Grazoprevir/Elbasvir (n = 111) 99% Open-label period Placebo (n = 113) Grazoprevir/Elbasvir (n = 113) 98% Grazoprevir/elbasvir dosed orally 100 mg/50 mg once daily. This study also included a pharmacokinetic analysis (n = 11) in which pts were treated as in the randomized grazoprevir/elbasvir study group. 76% on dialysis 34% with diabetes 52% GT1a, 48% GT1b 6% cirrhosis *Modified full analysis set population. CKD, chronic kidney disease; GT, genotype; HCV, hepatitis C virus; SVR, sustained virologic response. Roth D, et al. Lancet. 2015;386:1537-1545 Roth D, et al. Kidney Week 2015. Abstract SA-PO1100. Slide credit: clinicaloptions.com
Daclatasvir + Sofosbuvir Genotype 1a or 1b, treatment naive or experienced, without cirrhosis DCV + SOF, 12 wks Genotype 1a or 1b, treatment naive or experienced, with compensated cirrhosis DCV + SOF ± RBV, 24 wks* *Listed as “alternative” regimen DCV, daclatasvir; RBV, ribavirin; SOF, sofosbuvir. Slide credit: clinicaloptions.com AASLD/IDSA. HCV guidelines. April 2016.
DCV + SOF ± RBV for 24 Wks in GT1 Pts With Advanced Liver Disease SVR12 by Genotype 100 100 98 98 98 97 97 96 96 92 91 89 90 80 60 SVR12 (%) 40 20 GT, genotype; DCV, daclatasvir; mITT, modified intent to treat; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response. All GT1 GT1a GT1b As observed DCV + SOF DCV + SOF + RBV mITT DCV + SOF DCV + SOF + RBV Slide credit: clinicaloptions.com Welzel T, et al. EASL 2016. Abstract SAT-275.
Ombitasvir/Paritaprevir/Ritonavir + Dasabuvir Genotype 1a, treatment naive or experienced No cirrhosis: OBV/PTV/RTV + DSV + RBV, 12 wks With compensated cirrhosis: OBV/PTV/RTV + DSV + RBV, 24wks* RAV testing not indicated Genotype 1b, with/without compensated cirrhosis, treatment naive or experienced OBV/PTV/RTV + DSV, 12 wks DSV, dasabuvir; OBV, ombitasvir; PTV, paritaprevir; RAV, resistance associated variant; RBV, ribavirin; RTV, ritonavir. *Listed as “alternative” regimen. Slide credit: clinicaloptions.com AASLD/IDSA. HCV guidelines. April 2016.
TURQUOISE III: 12 Wks of OBV/PTV/RTV + DSV Without RBV in Cirrhotic GT1b Pts Virologic Response 100 100 100 100 100 80 60 Pts (%) 40 20 n/N = 60/60 60/60 60/60 60/60 RVR EOTR SVR4 SVR12 AASLD, American Association for the Study of Liver Diseases; DSV, dasabuvir; EOTR, end of treatment viral response; GT, genotype; OBV, ombitasvir; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir; RVR, rapid viral response; SVR, sustained virologic response. AASLD guidance now recommends OBV/PTV/RTV + DSV 12 wks without RBV for GT1b cirrhotics Still need 24 wks + RBV for GT1a cirrhotics, naive or experienced Poordad F, et al. AASLD 2015. Abstract 1051. AASLD/IDSA. HCV Guidance. April 2016. Slide credit: clinicaloptions.com
Real-World Efficacy of OBV/PTV/RTV ± DSV ± RBV: German HCV Registry Cohort Efficacy population (complete follow-up): n = 543; safety population (initiated treatment): n = 1017 GT1: 88%; GT4: 12%; cirrhosis: 22% (CTP B/C: 7%); tx experienced: 59% 100 97 96 97 95 93 96 100 96 98 96 100 80 *Includes 13 pts with mixed or unknown GT1 subgenotype infection, all of whom achieved SVR. 60 SVR24 (%) 40 20 BOC, boceprevir; CTP, Child-Turcotte-Pugh; DSV, dasabuvir; GT, genotype; HCV, hepatitis C virus; IFN, interferon; OBV, ombitasvir; pegIFN, peginterferon; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir; SVR, sustained virologic response; TVR, telaprevir; tx, treatment. 365/378 108/113 246/ 254 51/ 51 121/ 127 26/ 28 93/ 97 2/ 2 200/208 268/ 274 46/ 48 n/N = GT1 Total* GT1 Total* (peg)IFN ± RBV GT1a GT1b GT4 GT1a GT1b GT4 Naive TVR/BOC + pegIFN + RBV Without Cirrhosis With Cirrhosis Slide credit: clinicaloptions.com Hinrichsen H, et al. EASL 2016. Abstract GS07.
Real-World Efficacy of OBV/PTV/RTV ± DSV ± RBV: Israeli Cohort Efficacy population (complete follow-up): n = 432; safety population (initiated treatment): n = 661 GT1: 100%; cirrhosis: 62% (CTP A/B: 98.5%/1.5%); tx exp’d: 62% Post LT: n = 22 SVR12 mITT/overall: 82%/86%; 4 discontinued due to serious AEs, one of which achieved SVR 99 99 100 80 No cirrhosis Cirrhosis Pts With Undetectable HCV RNA (%) 60 40 AE, adverse event; CTP, Child-Turcotte-Pugh; DSV, dasabuvir; GT, genotype; LT, liver transplantation; mITT, modified intent to treat; OBV, ombitasvir; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir; SVR, sustained virologic response; tx, treatment. 20 161/ 163 251/ 253 *Excludes pts who did not achieve SVR12 for reasons other than virologic failure. 161/ 163 251/ 253 n/N = SVR12 (mITT*) Slide credit: clinicaloptions.com Zuckerman E, et al. EASL 2016. Abstract PS004.
Real-World Safety of OBV/PTV/RTV ± DSV ± RBV: German and Israeli Cohorts Most common AEs across both cohorts[1,2]: fatigue, pruritus, headache, insomnia, nausea, diarrhea (Israeli), anemia (German) Serious AE: 2.1% to 3.8% D/c for AE: 1.5% to 3.0% 3 deaths deemed unrelated to HCV therapy: stroke, MI, multiple organ failure In Israeli cohort, 20 pts discontinued for AEs[2] Serious AE: n = 12 Decompensation: n = 8 In Israeli cohort, several factors identified as significant predictors of hepatic decompensation[2] Factor P Value Age older than 75 yrs .005 Platelets < 90,000/mL .03 Albumin < 3.5 g/dL .048 CTP score ≥ 7 .07 MELD score > 10 .01 Previous decompensation < .001 AE, adverse event; CTP, Child-Turcotte-Pugh; D/c, discontinued; DSV, dasabuvir; HCV, hepatitis C virus; MELD, Model for End-Stage Liver Disease; MI, myocardial infarction; OBV, ombitasvir; PTV, paritaprevir; RBV, ribavirin; RTV, ritonavir. 1. Hinrichsen H, et al. EASL 2016. Abstract GS07. 2. Zuckerman E, et al. EASL 2016. Abstract PS004. Slide credit: clinicaloptions.com
Ledipasvir/Sofosbuvir for GT1 Tx-Naive Noncirrhotics With HCV RNA < 6 M IU/mL: Are 8 wks sufficient? Or are 12 wks better? Established by retrospective analysis of ION-3 Many clinicians were initially uncomfortable What do “real-world” data show? GT, genotype; Tx, treatment. Slide credit: clinicaloptions.com
8 vs 12 Wks of LDV/SOF in Pts With GT1 HCV: HCV-TARGET and TRIO Network Treatment-naive, noncirrhotic pts with GT1 HCV HCV RNA < 6 M IU/mL in HCV-TARGET HCV-TARGET[1] TRIO Network[2] 97 97 100 100 95 96 80 80 60 60 SVR12 (%) SVR12 (%) 40 40 GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; SOF, sofosbuvir; SVR, sustained virologic response. 20 20 n/N = 127/131 187/192 251/263 604/632 8 Wks 8 Wks 8 Wks 12 Wks 1. Terrault N, et al. AASLD 2015. Abstract 94. 2. Curry M, et al. AASLD 2015. Abstract 1046. Slide credit: clinicaloptions.com
8 Wks of LDV/SOF in Pts With GT1 HCV: German Real-World Single-Center Study Pts noncirrhotic (100%) and primarily treatment naive (97%), GT1 (98%), and HCV RNA < 6 M IU/mL (96%) 99 100 80 60 SVR12 (%) 40 GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; SOF, sofosbuvir; SVR, sustained virologic response. 20 n/N = 127/128 8 Wks Slide credit: clinicaloptions.com Buggisch P et al, EASL 2016. Abstract SAT-242.
LDV/SOF: SVR12 by Treatment Regimen and Duration in Pts Without Cirrhosis Pooled data from multiple trials, HCV RNA < 6 M IU/mL in 8-wk arm With RAVs No RAVs 98 99 99 99 100 80 60 SVR12 (%) 40 LDV, ledipasvir; RAV, resistance associated variant; SOF, sofosbuvir; SVR, sustained virologic response. 20 n/N = 30/32 107/108 187/189 504/509 8 Wks 12 Wks Slide credit: clinicaloptions.com Zeuzem S, et al. AASLD 2015. Abstract 91.
PPIs and Ledipasvir: Does Acid Suppression Matter? PPI, proton pump inhibitor.
HCV-TARGET: Effect of PPI Use? Pts treated according to local standards of care at 44 academic/ 17 community medical centers in North America/Europe Virologic outcome known for 1074 pts SVR12 According to Baseline PPI Use PPI: No PPI: Yes 98 98 100 80 60 40 20 93 93 SVR12 (%) LDV, ledipasvir; PPI, proton pump inhibitor; SOF, sofosbuvir; SVR, sustained virologic response. 122/ 124 28/ 30 456/ 464 151/ 163 n/N = 8-Wk LDV/SOF 12-Wk LDV/SOF Slide credit: clinicaloptions.com Terrault N, et al. AASLD 2015. Abstract 94.
TRIO Network: No Effect of PPI Use? Real-world data from 2034 pts with GT1 HCV receiving LDV/SOF A per protocol analysis (n = 1979) showed no effect of PPIs on SVR SVR12 According to Baseline PPI Use 98 100 98 97 99 100 80 60 40 20 97 PPI: No PPI: Yes GT, genotype; HCV, hepatitis C virus; LDV, ledipasvir; PPI, proton pump inhibitor; SOF, sofosbuvir; SVR, sustained virologic response. SVR12 (%) 230/234 41/ 41 1024/1045 287/297 243/246 113/116 n/N = 12 Wks 24 Wks 8 Wks Slide credit: clinicaloptions.com Afdhal N, et al. EASL 2016. Abstract LBP519.
TRIO Network: Predictors of Response to LDV/SOF by PPI Usage Per protocol analysis (n = 1979) n = 454 97% PPI drug Dexlansoprazole (n = 10) Esomeprazole (n = 48) Lansoprazole (n = 26) P = .799 Omeprazole (n = 288) “Caution with use of high dose PPIs with LDV/SOF” Pantoprazole (n = 77) Rabeprazole (n = 5) PPI dose Low (n = 282) P = .965 High (n = 172) LDV, ledipasvir; PPI, proton pump inhibitor; SOF, sofosbuvir. PPI frequency Once daily (n = 420) P = .030 Twice daily (n = 34) 80% 90% 100% Slide credit: clinicaloptions.com Afdhal N, et al. EASL 2016. Abstract LBP519.
New Regimens
VEL/SOF + GS-9857 for 6 or 8 Wks in Treatment-Naive Pts With GT1-6 HCV Genotype 1 Genotypes 1-6 No Cirrhosis Cirrhosis 96 100 94 100 100 81 79 71 80 80 60 60 SVR (%) SVR (%) 40 40 20 20 n/N = 53/67 95/99 25/35 36/36 31/33 25/31 No RBV 6 Wks No RBV 8 Wks No RBV 6 Wks No RBV 8 Wks No RBV 8 Wks RBV 8 Wks 8 wks of VEL/SOF + GS9857 highly effective including pts with RAVs and cirrhosis Single tablet QD in phase III 6 wks had high relapse No benefit of RBV with 8 wks Will the triplet be used as primary first-line treatment or as salvage treatment for persons who fail current DAAs? DAA, direct-acting antiviral; GT, genotype; HCV, hepatitis C virus; QD, once daily; RAV, resistance associated variant; RBV, ribavirin; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir. Slide credit: clinicaloptions.com Gane EJ, et al. EASL 2016. Abstract SAT-138.
VEL/SOF + GS-9857 for 12 Wks in Treatment-Experienced GT1-6 HCV BL Characteristics (N = 128) VEL/SOF + GS-9857 Cirrhosis, n (%) 61 (48) Mean HCV RNA, log10 IU/mL (range) 6.3 (3.8-8.1) HCV genotype, n (%) 1 63 (49) 2 21 (16) 3 35 (27) 4/6 9 (7) DAA experience, n (%) None (GT2-6 only) 27 (21) 1 DAA class 36 (28) ≥ 2 DAA classes 65 (51) 99 100 100 80 60 SVR12 (%) 40 20 n/N = 127/128 63/63 BL, baseline; DAA, direct-acting antiviral; GT, genotype; HCV, hepatitis C virus; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir. Overall GT1 1 pt relapsed at posttreatment Wk 8 Slide credit: clinicaloptions.com Lawitz E, et al. EASL 2016. Abstract PS008.
SURVEYOR-I/II: ABT-493 + ABT-530 for 8 or 12 Wks in Pts With GT1 or 2 HCV Open-label, treatment naive or pegIFN/RBV experienced SVR12 in Pts With GT1 HCV 8 wks 12 wks 100 97 96 100 100 80 80 60 60 SVR12 (%) SVR12 (%) 40 40 GT, genotype; HCV, hepatitis C virus; ITT, intent to treat; mITT, modified intent to treat; pegIFN, peginterferon; RBV, ribavirin; SVR, sustained virologic response. 20 20 n/N = 33/34 33/33 26/27 ITT mITT Cirrhosis[2] No Cirrhosis[1] 1. Poordad F, et al. EASL 2016. Abstract SAT-157. 2. Gane EJ, et al. EASL 2016. Abstract SAT-135. Slide credit: clinicaloptions.com
C-CREST 1 and 2: MK-3682/GZR/MK-8408 for 8 Wks in Tx-Naive Noncirrhotic Pts GT1, 2, or 3 without cirrhosis (N = 240) In GT1 arm, no impact of baseline NS5A, NS3, or NS5B RAVs on SVR12 100 100 87 80 60 40 MK-3682 (300 mg) + GZR + MK-8408 MK-3682 (450 mg) + GZR + MK-8408 20 n/N = 24/24 20/23 GT, genotype; GZR, grazoprevir; RAV, resistance associated variant; SVR, sustained virologic response; Tx, treatment. Genotype 1 Slide credit: clinicaloptions.com Gane EJ, et al. EASL 2016. Abstract 139.
Conclusions 5 highly effective regimens approved for GT1 HCV Newest is GZR/EBR, which requires RAV testing in GT1a Need for extended therapy and/or RBV in cirrhotics depending on regimen, GT1 subtype, and prior treatment status Real-world data reflect efficacy in clinical trials Data support 8 wks of LDV/SOF in GT1 treatment-naive noncirrhotics with HCV RNA < 6 M IU/mL High-dose PPIs should be avoided with LDV (same likely to be the case with VEL based on clinical trial designs) GT, genotype; GZR, grazoprevir; HCV, hepatitis C virus; LDV, ledipasvir; PPI, proton pump inhibitor; RAV, resistance associated variant; RBV, ribavirin; SOF, sofosbuvir; VEL, velpatasvir. Slide credit: clinicaloptions.com
New Regimens in Development Promising regimens Second-generation 2-drug regimen of ABT-493/ ABT-530 Triplet regimens of PI/NS5A/Nuc New regimens may offer 8-week option for noncirrhotics High SVR rates in DAA failures DAA, direct-acting antiviral; Nuc, nucleotide analog; PI, protease inhibitor; SOF, sofosbuvir; SVR, sustained virologic response; VEL, velpatasvir. Slide credit: clinicaloptions.com
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