- Email: [email protected]
Characterization of novel GT-1b resistant-associated substitutions (RASs) selected by NS5A inhibitor-based regimens
POSTER PRESENTATIONS Conclusions: Viral eradication doesn’t seem to be associated with increased risk of drop-out due to neoplastic disease-progression in HCV-HCC patients awaiting LT. Therefore, DAAs treatment can be safely offered to this patients population. SAT-270 Results of hepatitis C treatment program among people who inject drugs S. Filippovych1, O. Burgay1, I. Pavlyiuk1. 1TPSM, ICF “Alliance for Public Health”, Kyiv, Ukraine E-mail: [email protected] Background and Aims: According to WHO data in Ukraine, the approximate hepatitis C (HCV) infection rate among general population is 8.9% (which constitutes over 3.5 million individuals). An estimated number of people who inject drugs (PWID) in Ukraine is 310,000. HCV prevalence among PWID in Ukraine reaches 55%. HCV/HIV co-infection is registered in 38.4% of all newly registered HIV cases. Methods: Starting from June 2015, ICF “Alliance for Public Health” with support of the Ministry of Health of Ukraine organized HCV treatment program with direct-active antiviral – sofosbuvir (SOF) for HCVinfected PWID and representatives of other vulnerable populations using community-involved model (CIM) of treatment provision. HCV treatment was arranged in 19 healthcare facilities (HCFs) in 16 regions of Ukraine in collaboration with 15 non-governmental organizations. Multidisciplinary team (doctor/nurse/case-manager) was formed at each HCF. Within the CIM, case-managers provide support and links to integrated services (diagnostic and treatment of HIV, opioid substitution therapy (OST), and prevention of HCV re-infection). Results: As of November 1 2016, overall 1203 patients were enrolled in HCV treatment, 80% (N = 964) of them are PWID. 79% (N = 761) of all PWID were co-infected HCV/HIV, 97% (N = 737) received antiretroviral therapy (ARV), fibrosis stage in 93% (N = 902) of patients is ≥F2, 12% (N = 116) of patients were treatment experienced, 10% (N = 97) were OST patients (methadone and buprenorphine). 546 PWID achieved sustainable viral response at 12 weeks post-treatment (SVR 12w) point, including 4% (N = 22) drop-out cases. SVR 12w among PWID patients was achieved in 89% (N = 488). Genotypes distribution is 50% (N = 271) G1, 6% (N = 36) G2, 42% (N = 230) G3, 2% (N = 9) G4. 12-week treatment regimens were applied for 88% patients: SOF + RBV + Peg-IFN during 12 weeks was used in 82% (N = 448) of patients – SVR 12w was achieved in 92% (N = 410); and SOF + RBV during 12 weeks was used in 6% (N = 34) of patients – SVR 12w was achieved in 79% (N = 27). 10% (N = 56) of patients received SOF + RBV during 24 weeks, SVR 12w – 77% (N = 43). The rest 2% (N = 8) of patients received SOF in combination with daclatasvir with or without RBV, SVR 12w – 100% (N = 8). Conclusions: Short-term treatment regimens and multidisciplinary treatment approach within the CIM result in high level of adherence to HCV treatment and high cure rate among PWID patients. SAT-271 On-treatment HCV RNA monitoring is not a cost-effective means of identifying non-adherence and has no predictive value S. Demma1, W. Rosenberg1, D. Macdonald1. 1Institute of Liver and Digestive Health, University College London, London, United Kingdom E-mail: [email protected] Background and Aims: The high cost of directly-acting antiviral (DAA) treatment for HCV means local guidelines often mandate frequent HCV RNA testing on treatment to detect non-adherence or allow earlytermination of treatment in on-treatment relapse. It is unclear whether this monitoring is sensitive or cost-effective for this purpose. An HCV RNA increase of >1 log from an on-treatment nadir may indicate either non-adherence or viral breakthrough. We aimed to determine the frequency of this event in a retrospective cohort study of patients treated with DAA. We also examined whether slow responses
to treatment (HCV RNA quantifiable at week 2) were more common in patients with advanced disease and if this predicted relapse. Methods: We analysed viral loads, disease stage, HIV status, treatment experience, liver transplant status and outcome in 547 patients who underwent baseline and on-treatment testing on at least 3 occasions during treatment (total 3,957 HCV RNA tests) between May 2014 and June 2016 at the Royal Free London NHS Trust). Results: 4 patients had a viral load increase >1 log from an ontreatment nadir all of which occurred at week 8. One of these was suspected to be non-adherent and with close supervision achieved a full response at end of treatment and sustained virological response (SVR) at week 12. 3 had on-treatment relapses despite adequate adherence. Compared with a control group of non-cirrhotic patients, proportions of patients with a quantifiable HCV RNA at day 10–20 were greater in patients with decompensated (62% vs 47%, p = 0.0279 two-tailed χ2 test) and compensated cirrhosis (63% vs 47%, p = 0.002). HIV, transplant and treatment experience status had no significant impact on viral load at week 2 independently of disease stage. Across the whole cohort, post-treatment relapsers did not have a significantly higher proportion of quantifiable viral loads at any time point on treatment compared with those with an SVR 12 weeks after treatment. Conclusions: We estimate the cost of on-treatment viral load monitoring in this cohort to be €231,000. Only one patient was identified with poor adherence by this means. On-treatment relapses were all identified after dispensing their final 4 weeks of treatment. On-treatment HCV RNA monitoring is not a cost-effective or costsaving method of identifying non-adherence or on-treatment breakthrough respectively and has no predictive value with regard to treatment outcome. SAT-272 Characterization of novel GT-1b resistant-associated substitutions (RASs) selected by NS5A inhibitor-based regimens S. Fourati1,2, F. Donati1,2, A. Soulier1,2, C. Hézode3, L. Poiteau1,2, L. Ollier4, H. Danso1,2, A. Ahmed-Belkacem1,2, S. Chevaliez1,2, J.-M. Pawlotsky1,2. 1Virology, INSERM U955; 2Virology Department, National Reference Center for Viral Hepatitis B, C and D; 3Hepatology, INSERM U955, Créteil; 4Virology, Archet2 Hospital, Nice, France E-mail: [email protected] Background and Aims: Given the long-term persistence of HCV NS5A RASs, retreatment of patients failing NS5A inhibitor-based regimens is challenging. The incidence and nature of NS5A RASs have been well-characterized in clinical trials. However, resistance patterns in real-world patients can substantially differ. The French National Reference Center for Viral Hepatitis B, C and D performs HCV resistance testing in patients failing DAA-containing regimens across the country. NS5A substitutions at positions involved in resistance to NS5A inhibitors never described so far were detected and fully characterized. Methods: A total of 40 patients infected with HCV GT-1b failing an NS5A inhibitor-based regimen were included. NS5A sequences were assessed at baseline and at treatment failure by means of population sequencing. Nine known RAS positions located in domain I of NS5A were analyzed (residues 28, 29, 30, 31, 32, 58, 62, 92 and 93). Never reported AA substitutions at these positions were introduced into the Con-1 replicon to evaluate the susceptibility of the corresponding GT-1b NS5A variants to NS5A inhibitors. Results: Thus far unreported emerging substitutions in NS5A located at known RAS positions were identified in 2 patients. In patient 1, L28I co-emerged along with pre-existent R30S (and L31M) after the failure of 12 weeks of sofosbuvir (SOF) plus daclatasvir (DCV). In the replicon model, the combination of L28I and R30S conferred a 60-fold increase in DCV EC50, in the same order as the triple mutant L28I/R30S/L31M (45-fold). The replication capacities of these mutants were in the same order as that of WT virus (128% and 114%, respectively). In patient 2, the novel R30N substitution was detected along with the
Journal of Hepatology 2017 vol. 66 | S543–S750
S737
POSTER PRESENTATIONS well-known L31M and Y93H RASs after the failure of 12 weeks of SOF and ledipasvir. R30N slightly increased the level of resistance to DCV induced by L31M (51-fold vs. 26-fold for the double mutant vs. L31M alone). The level of resistance was much greater (>4,000-fold) when R30N was combined with both L31M and Y93H. The replication capacities of the double and triple mutants were lower than that of WT virus (33% and 38%, respectively). Conclusions: We characterized novel substitutions at known NS5A RAS positions individually conferring moderate resistance to NS5A inhibitors, but susceptible to synergize with other NS5A RASs. New low-frequency resistance patterns observed in real-world settings should be more widely characterized and tested in vitro towards the next generation of NS5A inhibitors. SAT-273 Safety and efficacy of glecaprevir/pibrentasvir in adults with chronic hepatitis C virus infection genotype 1–6 and chronic kidney disease: an integrated analysis S. Pol1, P. Pockros2, D. Pugatch3, N. Brau4, C. Landis5, M. Elkhashab6, J. Sasadeusz7, A. Tran8, Y. Hu3, M. Kosloski3, F. Mensa3. 1Groupe Hospitalier Cochin-Saint Vincent De Paul, Paris, France; 2Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla; 3Abbvie, North Chicago; 4James J. Peters VA Medical Center, Bronx; 5Division of Gastroenterology, University of Washington, Seattle, United States; 6 Toronto Liver Center, Toronto, Canada; 7Royal Melbourne Hospital, Melbourne, Australia; 8Digestive Center, University Hospital of Nice, Nice, France E-mail: [email protected] Background and Aims: Glecaprevir (GLE, formerly ABT-493, identified by AbbVie and Enanta) and pibrentasvir (PIB, formerly ABT530), collectively G/P, are two pangenotypic DAAs that have potent activity against HCV NS3/4A and NS5A, respectively. Neither compound undergoes significant renal excretion which makes them potentially suitable for patients with renal disease. Phase 1 studies demonstrated no clinically relevant increases in the exposure of G/P in patients with renal disease compared to those with normal renal function. Here we report on the safety and efficacy of G/P administered for 8 or 12 weeks in GT1-GT6 HCV-infected patients as a function of chronic kidney disease (CKD) stage. Methods: In this analysis, patients enrolled in all phase 2 and 3 studies were stratified based on CKD stage and treatment duration. Patients had GT1-6 chronic HCV infection and were either treatmentnaïve or treatment-experienced. All patients were treated with G/P (300 mg/120 mg) once daily for 8 or 12 weeks. CKD Stage
SVR12 n/N (%)
4 or 5 3 2 1
8-Week Treatment N/A 16/17 (94.1) 407/413 (98.5) 378/392 (96.4)
SVR12 n/N (%) 12-Week Treatment 101/103 (98.1) 18/18 (100) 581/593 (98.0) 622/633 (98.3)
were considered unrelated to study drugs and associated with the patients’ underlying comorbidities. No significant change in renal function from baseline to post-treatment week 12 was observed in patients with or without severe renal impairment. These results demonstrate the favorable safety and efficacy profile of G/P across all CKD stages, and that the presence of renal impairment has no impact on the efficacy of this pangenotypic regimen. SAT-274 Sofosbuvir-based all-oral regimens for patients with chronic hepatitis C genotype 2 infection: integrated analysis of eleven clinical studies S. Zeuzem1, K.-H. Han2, S.-H. Ahn2, Y.-S. Lim3, J.-H. Kao4, W.-L. Chuang5, M. Omata6, F. Abramov7, G. Crans7, J. Llewellyn7, M. Natha7, S. De-Oertel7, D. Brainard7, G.R. Foster8, E.J. Gane9, E. Lawitz10, S.B. Ho11, I.M. Jacobson12. 1Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; 2Yonsei University College of Medicine; 3Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, South; 4Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei; 5Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6Yamanashi Prefectural Central Hospital, Yamanashi, Japan; 7Gilead Sciences, Inc., Foster City, CA, United States; 8Royal London Hospital, London, United Kingdom; 9 Auckland Clinical Studies Limited, Auckland, New Zealand; 10Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX; 11VA San Diego Healthcare System, San Diego, CA; 12Mount Sinai Beth Israel, New York, NY, United States E-mail: [email protected] Background and Aims: Hepatitis C virus (HCV) genotype 2 (GT2) infection represents the third most common HCV genotype worldwide. AASLD/IDSA, EASL and APASL guidelines recommend sofosbuvir (SOF) based regimens for the treatment of patients with HCV GT2. This integrated analysis evaluated the efficacy and safety of various 12 and 16 week SOF-based all-oral regimens for HCV GT2 from eleven Phase 2, 3 and 4 clinical studies. Methods: Treatment naïve (TN) and/or treatment experienced (TE) patients with HCV GT2 who participated in 11 clinical trials including 2 conducted in Asia, 1 US Veterans Affairs study, and 8 multi-regional phase 3 studies. Patients were treated with SOF in combination with ribavirin (RBV) for 12 or 16 weeks or with the NS5A inhibitors ledipasvir (LDV) or velpatasvir (VEL) for 12 weeks. Efficacy and safety among the 4 different regimens are compared. There were 855 patients who received SOF + RBV for 12 weeks from 8 studies, 47 patients who received SOF + RBV for 16 weeks from 2 studies, 26 patients who received LDV/SOF for 12 weeks from 1 study and 238 patients who received SOF/VEL from 2 studies. Table 1: SVR12 Rates
% (n/N) Study
SOF + RBV
LDV/SOF
SOF/VEL
SOF + RBV 12 Week
16 week
12 week
12 week
(N = 855)
(N = 47)
(N = 26)
(N=238)
FUSION,
LEPTON
ASTRAL-1,
FISSION,
JAPAN,
POSITRON
KOREA/
VALOR
BOSON
ASTRAL-2
FUSION, VALENCE, TAIWAN
Results: A total of 2,169 patients were included in this analysis. Table 1 shows the efficacy by treatment duration and CKD stage. The most common AEs (≥10%) were headache and fatigue. Grouped in CKD stages 1 (n = 1025), 2 (n = 1006), 3 (n = 3 5) and 4–5 (n = 103), serious AEs were experienced by 1.9%, 2.6%, 5.6% and 24.0% of patients, respectively, none of which were considered study-drug related; 0.2%, 0.6%, 1.4% and 4.2% patients discontinued study-drug due to an AE; and 1, 1, 0 and 1 events of death occurred. The mean change in eGFR (mL/sec/1.73 m2) from baseline to post-treatment week 12 was −0.04 ± 0.21 in those with severe renal impairment and 0.00 ± 0.04 in those without severe renal impairment. Conclusions: G/P administered once daily for 8 or 12 weeks was highly efficacious and well tolerated in patients including those with advanced CKD. Serious AEs in those with severe renal impairment S738
ASTRAL -2 Overall
93% (392/420)
98% (360/369)
79% (52/66) 92% (43/47)
96% (25/26) 99.6%* (237/238) (1 LTFU)
Non-cirrhotic
95% (332/351)
98% (318/326)
−
100% (23/23) 96% (23/24) 99.5% (207/208) (1 LTFU)
Cirrhotic
87% (59/68)
98% (42/43)
79% (52/66) 83% (20/24)
100% (2/2)
100% (29/29)
Outcome for subjects without SVR12 On-treatment
0
0
0
0
0
0
6% (23/420)
2% (6/369)
17% (11/66)
9% (4/47)
0
0
virologic failure Relapse
*ASTRAL – 2: SOF/VEL SVR statistically superior to active comparator SOF + RBV for 12 weeks (p < 0.018) LTFU: Lost to follow-up
Journal of Hepatology 2017 vol. 66 | S543–S750
to treatment (HCV RNA quantifiable at week 2) were more common in patients with advanced disease and if this predicted relapse. Methods: We analysed viral loads, disease stage, HIV status, treatment experience, liver transplant status and outcome in 547 patients who underwent baseline and on-treatment testing on at least 3 occasions during treatment (total 3,957 HCV RNA tests) between May 2014 and June 2016 at the Royal Free London NHS Trust). Results: 4 patients had a viral load increase >1 log from an ontreatment nadir all of which occurred at week 8. One of these was suspected to be non-adherent and with close supervision achieved a full response at end of treatment and sustained virological response (SVR) at week 12. 3 had on-treatment relapses despite adequate adherence. Compared with a control group of non-cirrhotic patients, proportions of patients with a quantifiable HCV RNA at day 10–20 were greater in patients with decompensated (62% vs 47%, p = 0.0279 two-tailed χ2 test) and compensated cirrhosis (63% vs 47%, p = 0.002). HIV, transplant and treatment experience status had no significant impact on viral load at week 2 independently of disease stage. Across the whole cohort, post-treatment relapsers did not have a significantly higher proportion of quantifiable viral loads at any time point on treatment compared with those with an SVR 12 weeks after treatment. Conclusions: We estimate the cost of on-treatment viral load monitoring in this cohort to be €231,000. Only one patient was identified with poor adherence by this means. On-treatment relapses were all identified after dispensing their final 4 weeks of treatment. On-treatment HCV RNA monitoring is not a cost-effective or costsaving method of identifying non-adherence or on-treatment breakthrough respectively and has no predictive value with regard to treatment outcome. SAT-272 Characterization of novel GT-1b resistant-associated substitutions (RASs) selected by NS5A inhibitor-based regimens S. Fourati1,2, F. Donati1,2, A. Soulier1,2, C. Hézode3, L. Poiteau1,2, L. Ollier4, H. Danso1,2, A. Ahmed-Belkacem1,2, S. Chevaliez1,2, J.-M. Pawlotsky1,2. 1Virology, INSERM U955; 2Virology Department, National Reference Center for Viral Hepatitis B, C and D; 3Hepatology, INSERM U955, Créteil; 4Virology, Archet2 Hospital, Nice, France E-mail: [email protected] Background and Aims: Given the long-term persistence of HCV NS5A RASs, retreatment of patients failing NS5A inhibitor-based regimens is challenging. The incidence and nature of NS5A RASs have been well-characterized in clinical trials. However, resistance patterns in real-world patients can substantially differ. The French National Reference Center for Viral Hepatitis B, C and D performs HCV resistance testing in patients failing DAA-containing regimens across the country. NS5A substitutions at positions involved in resistance to NS5A inhibitors never described so far were detected and fully characterized. Methods: A total of 40 patients infected with HCV GT-1b failing an NS5A inhibitor-based regimen were included. NS5A sequences were assessed at baseline and at treatment failure by means of population sequencing. Nine known RAS positions located in domain I of NS5A were analyzed (residues 28, 29, 30, 31, 32, 58, 62, 92 and 93). Never reported AA substitutions at these positions were introduced into the Con-1 replicon to evaluate the susceptibility of the corresponding GT-1b NS5A variants to NS5A inhibitors. Results: Thus far unreported emerging substitutions in NS5A located at known RAS positions were identified in 2 patients. In patient 1, L28I co-emerged along with pre-existent R30S (and L31M) after the failure of 12 weeks of sofosbuvir (SOF) plus daclatasvir (DCV). In the replicon model, the combination of L28I and R30S conferred a 60-fold increase in DCV EC50, in the same order as the triple mutant L28I/R30S/L31M (45-fold). The replication capacities of these mutants were in the same order as that of WT virus (128% and 114%, respectively). In patient 2, the novel R30N substitution was detected along with the
Journal of Hepatology 2017 vol. 66 | S543–S750
S737
POSTER PRESENTATIONS well-known L31M and Y93H RASs after the failure of 12 weeks of SOF and ledipasvir. R30N slightly increased the level of resistance to DCV induced by L31M (51-fold vs. 26-fold for the double mutant vs. L31M alone). The level of resistance was much greater (>4,000-fold) when R30N was combined with both L31M and Y93H. The replication capacities of the double and triple mutants were lower than that of WT virus (33% and 38%, respectively). Conclusions: We characterized novel substitutions at known NS5A RAS positions individually conferring moderate resistance to NS5A inhibitors, but susceptible to synergize with other NS5A RASs. New low-frequency resistance patterns observed in real-world settings should be more widely characterized and tested in vitro towards the next generation of NS5A inhibitors. SAT-273 Safety and efficacy of glecaprevir/pibrentasvir in adults with chronic hepatitis C virus infection genotype 1–6 and chronic kidney disease: an integrated analysis S. Pol1, P. Pockros2, D. Pugatch3, N. Brau4, C. Landis5, M. Elkhashab6, J. Sasadeusz7, A. Tran8, Y. Hu3, M. Kosloski3, F. Mensa3. 1Groupe Hospitalier Cochin-Saint Vincent De Paul, Paris, France; 2Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla; 3Abbvie, North Chicago; 4James J. Peters VA Medical Center, Bronx; 5Division of Gastroenterology, University of Washington, Seattle, United States; 6 Toronto Liver Center, Toronto, Canada; 7Royal Melbourne Hospital, Melbourne, Australia; 8Digestive Center, University Hospital of Nice, Nice, France E-mail: [email protected] Background and Aims: Glecaprevir (GLE, formerly ABT-493, identified by AbbVie and Enanta) and pibrentasvir (PIB, formerly ABT530), collectively G/P, are two pangenotypic DAAs that have potent activity against HCV NS3/4A and NS5A, respectively. Neither compound undergoes significant renal excretion which makes them potentially suitable for patients with renal disease. Phase 1 studies demonstrated no clinically relevant increases in the exposure of G/P in patients with renal disease compared to those with normal renal function. Here we report on the safety and efficacy of G/P administered for 8 or 12 weeks in GT1-GT6 HCV-infected patients as a function of chronic kidney disease (CKD) stage. Methods: In this analysis, patients enrolled in all phase 2 and 3 studies were stratified based on CKD stage and treatment duration. Patients had GT1-6 chronic HCV infection and were either treatmentnaïve or treatment-experienced. All patients were treated with G/P (300 mg/120 mg) once daily for 8 or 12 weeks. CKD Stage
SVR12 n/N (%)
4 or 5 3 2 1
8-Week Treatment N/A 16/17 (94.1) 407/413 (98.5) 378/392 (96.4)
SVR12 n/N (%) 12-Week Treatment 101/103 (98.1) 18/18 (100) 581/593 (98.0) 622/633 (98.3)
were considered unrelated to study drugs and associated with the patients’ underlying comorbidities. No significant change in renal function from baseline to post-treatment week 12 was observed in patients with or without severe renal impairment. These results demonstrate the favorable safety and efficacy profile of G/P across all CKD stages, and that the presence of renal impairment has no impact on the efficacy of this pangenotypic regimen. SAT-274 Sofosbuvir-based all-oral regimens for patients with chronic hepatitis C genotype 2 infection: integrated analysis of eleven clinical studies S. Zeuzem1, K.-H. Han2, S.-H. Ahn2, Y.-S. Lim3, J.-H. Kao4, W.-L. Chuang5, M. Omata6, F. Abramov7, G. Crans7, J. Llewellyn7, M. Natha7, S. De-Oertel7, D. Brainard7, G.R. Foster8, E.J. Gane9, E. Lawitz10, S.B. Ho11, I.M. Jacobson12. 1Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany; 2Yonsei University College of Medicine; 3Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea, South; 4Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei; 5Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 6Yamanashi Prefectural Central Hospital, Yamanashi, Japan; 7Gilead Sciences, Inc., Foster City, CA, United States; 8Royal London Hospital, London, United Kingdom; 9 Auckland Clinical Studies Limited, Auckland, New Zealand; 10Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX; 11VA San Diego Healthcare System, San Diego, CA; 12Mount Sinai Beth Israel, New York, NY, United States E-mail: [email protected] Background and Aims: Hepatitis C virus (HCV) genotype 2 (GT2) infection represents the third most common HCV genotype worldwide. AASLD/IDSA, EASL and APASL guidelines recommend sofosbuvir (SOF) based regimens for the treatment of patients with HCV GT2. This integrated analysis evaluated the efficacy and safety of various 12 and 16 week SOF-based all-oral regimens for HCV GT2 from eleven Phase 2, 3 and 4 clinical studies. Methods: Treatment naïve (TN) and/or treatment experienced (TE) patients with HCV GT2 who participated in 11 clinical trials including 2 conducted in Asia, 1 US Veterans Affairs study, and 8 multi-regional phase 3 studies. Patients were treated with SOF in combination with ribavirin (RBV) for 12 or 16 weeks or with the NS5A inhibitors ledipasvir (LDV) or velpatasvir (VEL) for 12 weeks. Efficacy and safety among the 4 different regimens are compared. There were 855 patients who received SOF + RBV for 12 weeks from 8 studies, 47 patients who received SOF + RBV for 16 weeks from 2 studies, 26 patients who received LDV/SOF for 12 weeks from 1 study and 238 patients who received SOF/VEL from 2 studies. Table 1: SVR12 Rates
% (n/N) Study
SOF + RBV
LDV/SOF
SOF/VEL
SOF + RBV 12 Week
16 week
12 week
12 week
(N = 855)
(N = 47)
(N = 26)
(N=238)
FUSION,
LEPTON
ASTRAL-1,
FISSION,
JAPAN,
POSITRON
KOREA/
VALOR
BOSON
ASTRAL-2
FUSION, VALENCE, TAIWAN
Results: A total of 2,169 patients were included in this analysis. Table 1 shows the efficacy by treatment duration and CKD stage. The most common AEs (≥10%) were headache and fatigue. Grouped in CKD stages 1 (n = 1025), 2 (n = 1006), 3 (n = 3 5) and 4–5 (n = 103), serious AEs were experienced by 1.9%, 2.6%, 5.6% and 24.0% of patients, respectively, none of which were considered study-drug related; 0.2%, 0.6%, 1.4% and 4.2% patients discontinued study-drug due to an AE; and 1, 1, 0 and 1 events of death occurred. The mean change in eGFR (mL/sec/1.73 m2) from baseline to post-treatment week 12 was −0.04 ± 0.21 in those with severe renal impairment and 0.00 ± 0.04 in those without severe renal impairment. Conclusions: G/P administered once daily for 8 or 12 weeks was highly efficacious and well tolerated in patients including those with advanced CKD. Serious AEs in those with severe renal impairment S738
ASTRAL -2 Overall
93% (392/420)
98% (360/369)
79% (52/66) 92% (43/47)
96% (25/26) 99.6%* (237/238) (1 LTFU)
Non-cirrhotic
95% (332/351)
98% (318/326)
−
100% (23/23) 96% (23/24) 99.5% (207/208) (1 LTFU)
Cirrhotic
87% (59/68)
98% (42/43)
79% (52/66) 83% (20/24)
100% (2/2)
100% (29/29)
Outcome for subjects without SVR12 On-treatment
0
0
0
0
0
0
6% (23/420)
2% (6/369)
17% (11/66)
9% (4/47)
0
0
virologic failure Relapse
*ASTRAL – 2: SOF/VEL SVR statistically superior to active comparator SOF + RBV for 12 weeks (p < 0.018) LTFU: Lost to follow-up
Journal of Hepatology 2017 vol. 66 | S543–S750