Velpatasvir

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Diana M Brainard - One of the best experts on this subject based on the ideXlab platform.

  • sofosbuvir Velpatasvir voxilaprevir for patients with hcv who previously received a sofosbuvir Velpatasvir containing regimen results from a retreatment study
    Journal of Viral Hepatitis, 2019
    Co-Authors: Peter Ruane, Simone I Strasser, Diana M Brainard, Edward Gane, Robert H Hyland, Jiang Shao, Hadas Dvorysobol, Tram Tran, Luisa M Stamm, L Nyberg
    Abstract:

    This study evaluated 12-week retreatment with sofosbuvir/Velpatasvir/voxilaprevir in patients with chronic hepatitis C virus (HCV) infection who did not achieve sustained virologic response after previous treatment with a sofosbuvir- and Velpatasvir-containing regimen. All 31 patients maintained a sustained virologic response 12 weeks after the last sofosbuvir/Velpatasvir/voxilaprevir dose.

  • Sofosbuvir/Velpatasvir/Voxilaprevir for patients with HCV who previously received a Sofosbuvir/Velpatasvir-containing regimen: Results from a retreatment study.
    Journal of Viral Hepatitis, 2019
    Co-Authors: Peter Ruane, Simone I Strasser, Diana M Brainard, Edward Gane, Robert H Hyland, Jiang Shao, Tram Tran, Luisa M Stamm, Hadas Dvory-sobol, L Nyberg
    Abstract:

    : This study evaluated 12-week retreatment with sofosbuvir/Velpatasvir/voxilaprevir in patients with chronic hepatitis C virus (HCV) infection who did not achieve sustained virologic response after previous treatment with a sofosbuvir- and Velpatasvir-containing regimen. All 31 patients maintained a sustained virologic response 12 weeks after the last sofosbuvir/Velpatasvir/voxilaprevir dose.

  • Pharmacokinetics and Safety of Velpatasvir and Sofosbuvir/Velpatasvir in Subjects with Hepatic Impairment
    Clinical Pharmacokinetics, 2018
    Co-Authors: Erik Mogalian, Diana M Brainard, E Lawitz, Anu Osinusi, Lisa Moorehead, Bernard Murray, Kah Hiing John Ling, Robert Perry, Craig Curtis, Kenneth Lasseter
    Abstract:

    Background The pharmacokinetics and safety of Velpatasvir, a potent pangenotypic hepatitis C virus NS5A inhibitor, were evaluated in two hepatic impairment studies: a phase I study in hepatitis C virus-uninfected subjects and a phase III study (ASTRAL-4) in hepatitis C virus-infected patients. Methods In the phase I study, subjects with moderate or severe hepatic impairment (Child-Pugh-Turcotte Class B or C), and demographically matched subjects with normal hepatic function received a single dose of Velpatasvir 100 mg. Pharmacokinetics and safety assessments were performed, and pharmacokinetic parameters were calculated using non-compartmental methods and summarized using descriptive statistics and compared statistically by geometric least-squares mean ratios and 90% confidence intervals. In ASTRAL-4, subjects with decompensated cirrhosis (Child-Pugh-Turcotte Class B) were randomized to receive treatment with either sofosbuvir/Velpatasvir ± ribavirin for 12 weeks or sofosbuvir/Velpatasvir for 24 weeks. Pharmacokinetic and safety assessments were performed and pharmacokinetic parameters were calculated using a non-compartmental analysis and summarized using descriptive statistics and were compared to pharmacokinetics from ASTRAL-1 [subjects without cirrhosis or with compensated (Child-Pugh-Turcotte Class A) cirrhosis]. Results In the phase I study, plasma exposures (area under the concentration–time curve) were similar in subjects with Child-Pugh-Turcotte Class B ( n  = 10) or Child-Pugh-Turcotte Class C hepatic impairment ( n  = 10) compared with normal hepatic function ( n  = 13). Percent free Velpatasvir was similar in subjects without or with any degree of hepatic impairment. In the phase III study, Velpatasvir overall exposure (area under the concentration–time curve over the 24-h dosing interval; AUC_tau) was similar and sofosbuvir exposures were higher (~ 100%) for patients with Child-Pugh-Turcotte Class B hepatic impairment compared with the ASTRAL-1 population, which was not considered clinically relevant. Conclusions No sofosbuvir/Velpatasvir dose modification is warranted for patients with any degree of hepatic impairment.

  • sofosbuvir Velpatasvir for 12 weeks in genotype 1 4 hcv infected liver transplant recipients
    Journal of Hepatology, 2018
    Co-Authors: K Agarwal, John Mcnally, Luisa M Stamm, Lluis Castells, Beat Mullhaupt, W Rosenberg, Brian Mcnabb, S Arterburn, Gregory Camus, Diana M Brainard
    Abstract:

    Background & Aims Sofosbuvir, an NS5B inhibitor, combined with Velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1–6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1–4 HCV infection after liver transplant. Methods Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naive with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. Results A total of 79 patients were enrolled and treated in this study (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naive, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. Conclusions Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1–4 HCV-infected liver transplant recipients with and without cirrhosis. Lay summary Sofosbuvir/Velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus (HCV) infection. When patients with chronic HCV infection receive a liver transplant, the HCV infection usually recurs, and damages the transplanted liver. This study tested the effects of 12 weeks of sofosbuvir/Velpatasvir treatment in patients who had HCV recurrence after a liver transplant. Three months following the end of treatment, 96% of patients were cured of HCV infection. Clinical trial number: NCT02781571.

  • Sofosbuvir/Velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients.
    Journal of Hepatology, 2018
    Co-Authors: K Agarwal, John Mcnally, Luisa M Stamm, Lluis Castells, Beat Mullhaupt, W Rosenberg, Brian Mcnabb, S Arterburn, Gregory Camus, Diana M Brainard
    Abstract:

    Background & Aims Sofosbuvir, an NS5B inhibitor, combined with Velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1–6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1–4 HCV infection after liver transplant. Methods Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naive with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. Results A total of 79 patients were enrolled and treated in this study (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naive, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. Conclusions Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1–4 HCV-infected liver transplant recipients with and without cirrhosis. Lay summary Sofosbuvir/Velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus (HCV) infection. When patients with chronic HCV infection receive a liver transplant, the HCV infection usually recurs, and damages the transplanted liver. This study tested the effects of 12 weeks of sofosbuvir/Velpatasvir treatment in patients who had HCV recurrence after a liver transplant. Three months following the end of treatment, 96% of patients were cured of HCV infection. Clinical trial number: NCT02781571.

Anu Osinusi - One of the best experts on this subject based on the ideXlab platform.

  • deferred treatment with a fixed dose combination of sofosbuvir Velpatasvir for chronic hepatitis c virus genotype 1 2 4 and 6 infection
    Journal of Viral Hepatitis, 2019
    Co-Authors: T Asselah, M Davis, Bernard Willems, Stephen D Shafran, Evguenia S. Svarovskaia, Stefan Bourgeois, Philippe Mathurin, Mindie H Nguyen, K C Huang, Anu Osinusi
    Abstract:

    Sofosbuvir-Velpatasvir is approved for the treatment of chronic hepatitis C virus (HCV) infection. In this single-arm, open-label, phase 3, deferred treatment study, we investigated the efficacy and safety of sofosbuvir-Velpatasvir among patients randomized to the placebo group in the ASTRAL-1 study. Patients received sofosbuvir-Velpatasvir (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response 12 weeks after the end of therapy (SVR12). The primary safety endpoint was any adverse events (AEs) leading to the permanent discontinuation of study drug. Overall, 108/111 (97%, 95% confidence interval [CI], 92%-99%) achieved SVR12, and only one patient had virological failure. SVR12 was achieved by 61/63 (97%, 95%CI, 89%-100%) genotype 1 patients, 20/20 (100%; 95%CI, 83%-100%) with genotype 2, 19/19 (100%; 95%CI, 82%-100%) with genotype 4 and 8/9 (89%; 95% CI, 52%-100%) with genotype 6. All (19/19; 95%CI, 82-100) patients with cirrhosis and all (31/31, 95%CI, 89-100) with prior treatment experience achieved SVR12. The safety profile during treatment was similar to that observed in patients receiving placebo treatment. The most common AEs were headache, fatigue and nausea. One patient (1%) discontinued treatment due to an AE of gallbladder carcinoma, which was not considered related to treatment. Of five reported serious AEs, none were considered related to study drug. Sofosbuvir-Velpatasvir for 12 weeks was effective and well tolerated among untreated and previously treated patients with HCV genotype 1, 2, 4 or 6 infection, including those with compensated cirrhosis (ClinicalTrials.gov NCT02346721).

  • Pharmacokinetics and Safety of Velpatasvir and Sofosbuvir/Velpatasvir in Subjects with Hepatic Impairment
    Clinical Pharmacokinetics, 2018
    Co-Authors: Erik Mogalian, Diana M Brainard, E Lawitz, Anu Osinusi, Lisa Moorehead, Bernard Murray, Kah Hiing John Ling, Robert Perry, Craig Curtis, Kenneth Lasseter
    Abstract:

    Background The pharmacokinetics and safety of Velpatasvir, a potent pangenotypic hepatitis C virus NS5A inhibitor, were evaluated in two hepatic impairment studies: a phase I study in hepatitis C virus-uninfected subjects and a phase III study (ASTRAL-4) in hepatitis C virus-infected patients. Methods In the phase I study, subjects with moderate or severe hepatic impairment (Child-Pugh-Turcotte Class B or C), and demographically matched subjects with normal hepatic function received a single dose of Velpatasvir 100 mg. Pharmacokinetics and safety assessments were performed, and pharmacokinetic parameters were calculated using non-compartmental methods and summarized using descriptive statistics and compared statistically by geometric least-squares mean ratios and 90% confidence intervals. In ASTRAL-4, subjects with decompensated cirrhosis (Child-Pugh-Turcotte Class B) were randomized to receive treatment with either sofosbuvir/Velpatasvir ± ribavirin for 12 weeks or sofosbuvir/Velpatasvir for 24 weeks. Pharmacokinetic and safety assessments were performed and pharmacokinetic parameters were calculated using a non-compartmental analysis and summarized using descriptive statistics and were compared to pharmacokinetics from ASTRAL-1 [subjects without cirrhosis or with compensated (Child-Pugh-Turcotte Class A) cirrhosis]. Results In the phase I study, plasma exposures (area under the concentration–time curve) were similar in subjects with Child-Pugh-Turcotte Class B ( n  = 10) or Child-Pugh-Turcotte Class C hepatic impairment ( n  = 10) compared with normal hepatic function ( n  = 13). Percent free Velpatasvir was similar in subjects without or with any degree of hepatic impairment. In the phase III study, Velpatasvir overall exposure (area under the concentration–time curve over the 24-h dosing interval; AUC_tau) was similar and sofosbuvir exposures were higher (~ 100%) for patients with Child-Pugh-Turcotte Class B hepatic impairment compared with the ASTRAL-1 population, which was not considered clinically relevant. Conclusions No sofosbuvir/Velpatasvir dose modification is warranted for patients with any degree of hepatic impairment.

  • pharmacokinetics and safety of Velpatasvir and sofosbuvir Velpatasvir in subjects with hepatic impairment
    Clinical Pharmacokinectics, 2018
    Co-Authors: Erik Mogalian, Diana M Brainard, E Lawitz, Anu Osinusi, Lisa Moorehead, Kah Hiing John Ling, Robert Perry, Craig Curtis, Bernard P Murray, Kenneth Lasseter
    Abstract:

    Background The pharmacokinetics and safety of Velpatasvir, a potent pangenotypic hepatitis C virus NS5A inhibitor, were evaluated in two hepatic impairment studies: a phase I study in hepatitis C virus-uninfected subjects and a phase III study (ASTRAL-4) in hepatitis C virus-infected patients. Methods In the phase I study, subjects with moderate or severe hepatic impairment (Child-Pugh-Turcotte Class B or C), and demographically matched subjects with normal hepatic function received a single dose of Velpatasvir 100 mg. Pharmacokinetics and safety assessments were performed, and pharmacokinetic parameters were calculated using non-compartmental methods and summarized using descriptive statistics and compared statistically by geometric least-squares mean ratios and 90% confidence intervals. In ASTRAL-4, subjects with decompensated cirrhosis (Child-Pugh-Turcotte Class B) were randomized to receive treatment with either sofosbuvir/Velpatasvir ± ribavirin for 12 weeks or sofosbuvir/Velpatasvir for 24 weeks. Pharmacokinetic and safety assessments were performed and pharmacokinetic parameters were calculated using a non-compartmental analysis and summarized using descriptive statistics and were compared to pharmacokinetics from ASTRAL-1 [subjects without cirrhosis or with compensated (Child-Pugh-Turcotte Class A) cirrhosis]. Results In the phase I study, plasma exposures (area under the concentration-time curve) were similar in subjects with Child-Pugh-Turcotte Class B (n = 10) or Child-Pugh-Turcotte Class C hepatic impairment (n = 10) compared with normal hepatic function (n = 13). Percent free Velpatasvir was similar in subjects without or with any degree of hepatic impairment. In the phase III study, Velpatasvir overall exposure (area under the concentration-time curve over the 24-h dosing interval; AUCtau) was similar and sofosbuvir exposures were higher (~ 100%) for patients with Child-Pugh-Turcotte Class B hepatic impairment compared with the ASTRAL-1 population, which was not considered clinically relevant. Conclusions No sofosbuvir/Velpatasvir dose modification is warranted for patients with any degree of hepatic impairment.

  • sofosbuvir Velpatasvir in patients with hepatitis c virus genotypes 1 6 and compensated cirrhosis or advanced fibrosis
    Liver International, 2018
    Co-Authors: T Asselah, John Mcnally, Diana M Brainard, S Zeuzem, Anu Osinusi, Mark S Sulkowski, Graham R Foster, Stefan Bourgeois, S Pianko, Mani G Subramanian
    Abstract:

    Background & Aims Patients with chronic hepatitis C virus (HCV) infection and advanced fibrosis (Metavir F3) or cirrhosis (Metavir F4) have been identified as a priority group for immediate treatment. We evaluated the safety and efficacy of sofosbuvir-Velpatasvir in patients with HCV genotype 1-6 infection and compensated cirrhosis or advanced fibrosis. Methods This retrospective analysis included 501 patients with compensated cirrhosis or advanced fibrosis (F3/F4), as defined by >0.59 on Fibrotest, >9.5 kPa on Fibroscan, or F3/F4 (Metavir) or F4 (Ishak) on liver biopsy. Patients received sofosbuvir-Velpatasvir for 12 weeks. Sustained virological response 12 weeks after treatment (SVR12) was determined. Results Forty-four percent of patients had cirrhosis. SVR12 was achieved by 98% of patients (490/501; 95% CI, 96%-99%). SVR12 rates were 100% for HCV genotypes 2 (85/85), 4 (60/60), 5 (13/13), and 6 (20/20). SVR12 rates were 98% (167/170) in HCV genotype 1 patients and 95% (145/153) in HCV genotype 3 patients. Among patients with cirrhosis 96% (212/220) achieved SVR12, versus 99% (278/281) for those with advanced fibrosis. SVR12 was 98% (306/311) for treatment-naive patients and 97% (184/190) for treatment-experienced patients. No patients discontinued treatment due to adverse events. Eight patients reported nine serious adverse events; none was considered related to study procedures or drugs. Conclusions Sofosbuvir plus Velpatasvir is highly effective and safe for treating patients with HCV genotypes 1, 2, 3, 4, 5, or 6 and advanced fibrosis or compensated cirrhosis. This article is protected by copyright. All rights reserved.

  • Resistance analysis in patients with genotype 1-6 HCV infection treated with sofosbuvir/Velpatasvir in the phase III studies.
    Journal of Hepatology, 2017
    Co-Authors: Christophe Hezode, John Mcnally, Brian P Doehle, Hadas Dvory-sobol, Anu Osinusi, Evguenia S. Svarovskaia, Nancy Reau, Ragavi Shanmugam, Charlotte Hedskog, Diana M Brainard
    Abstract:

    Background & Aims The fixed-dose combination of sofosbuvir/Velpatasvir was highly efficacious in patients infected with genotype (GT)1–6 hepatitis C virus (HCV) in the ASTRAL studies. This analysis evaluated the impact of baseline resistance-associated substitutions (RASs) on treatment outcome and emergence of RASs in patients infected with HCV GT1-6 who were treated with sofosbuvir/Velpatasvir. Methods Non-structural protein 5A and 5B (NS5A and NS5B ) deep sequencing was performed at baseline and at the time of relapse for all patients treated with sofosbuvir/Velpatasvir for 12 weeks (n = 1,778) in the ASTRAL-1–3, ASTRAL-5 and POLARIS-2–3 studies. Results Patients with 37 known and 19 novel HCV subtypes were included in these analyses. Overall, 28% (range 9% to 61% depending on genotype) had detectable NS5A class RASs at baseline, using a 15% sequencing assay cut-off. There was no significant effect of baseline NS5A class RASs on sustained virologic response at week 12 (SVR12) with sofosbuvir/Velpatasvir; the SVR12 rate in the presence of NS5A class RASs was 100% and 97%, in patients with GT1a and GT1b infection, respectively, and 100% in patients with GT2 and GT4–6 infections. In GT3 infection, the SVR rate was 93% and 98% in patients with and without baseline NS5A class RASs, respectively. The overall virologic failure rate was low (20/1,778 = 1.1%) in patients treated with sofosbuvir/Velpatasvir. Single NS5A class resistance was observed at virologic failure in 17 of the 20 patients. Conclusions Sofosbuvir/Velpatasvir taken for 12 weeks once daily resulted in high SVR rates in patients infected with GT1–6 HCV, irrespective of baseline NS5A RASs. NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients. Lay summary Sofosbuvir/Velpatasvir taken once daily for 12 weeks resulted in high sustained virologic response rates in patients infected with HCV, irrespective of the presence of NS5A resistance-associated variants prior to treatment. Single class NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients.

John Mcnally - One of the best experts on this subject based on the ideXlab platform.

  • sofosbuvir Velpatasvir for 12 weeks in genotype 1 4 hcv infected liver transplant recipients
    Journal of Hepatology, 2018
    Co-Authors: K Agarwal, John Mcnally, Luisa M Stamm, Lluis Castells, Beat Mullhaupt, W Rosenberg, Brian Mcnabb, S Arterburn, Gregory Camus, Diana M Brainard
    Abstract:

    Background & Aims Sofosbuvir, an NS5B inhibitor, combined with Velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1–6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1–4 HCV infection after liver transplant. Methods Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naive with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. Results A total of 79 patients were enrolled and treated in this study (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naive, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. Conclusions Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1–4 HCV-infected liver transplant recipients with and without cirrhosis. Lay summary Sofosbuvir/Velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus (HCV) infection. When patients with chronic HCV infection receive a liver transplant, the HCV infection usually recurs, and damages the transplanted liver. This study tested the effects of 12 weeks of sofosbuvir/Velpatasvir treatment in patients who had HCV recurrence after a liver transplant. Three months following the end of treatment, 96% of patients were cured of HCV infection. Clinical trial number: NCT02781571.

  • Sofosbuvir/Velpatasvir for 12 weeks in genotype 1-4 HCV-infected liver transplant recipients.
    Journal of Hepatology, 2018
    Co-Authors: K Agarwal, John Mcnally, Luisa M Stamm, Lluis Castells, Beat Mullhaupt, W Rosenberg, Brian Mcnabb, S Arterburn, Gregory Camus, Diana M Brainard
    Abstract:

    Background & Aims Sofosbuvir, an NS5B inhibitor, combined with Velpatasvir, an NS5A inhibitor (SOF/VEL), produces high sustained virologic response rates 12 weeks after treatment (SVR12) in patients with genotype 1–6 HCV infection, and has no anticipated clinically relevant drug-drug interactions with immunosuppressants. This study evaluated the safety and efficacy of SOF/VEL in adults with recurrent chronic genotype 1–4 HCV infection after liver transplant. Methods Patients received SOF/VEL 400/100 mg daily for 12 weeks. Patients could be treatment experienced or treatment naive with no cirrhosis or with compensated cirrhosis. The primary endpoints were SVR12 and discontinuations due to adverse events. Results A total of 79 patients were enrolled and treated in this study (37 [47%] had genotype 1, 3 [4%] genotype 2, 35 [44%] genotype 3, and 4 [5%] genotype 4 HCV). Of these, 81% were male, 82% were white, 18% had compensated cirrhosis, and 59% were treatment experienced. The most commonly used immunosuppressants were tacrolimus (71%), mycophenolic acid (24%), cyclosporine (14%), and azathioprine (11%). Median (range) time from liver transplantation was 7.5 (0.3, 23.9) years. The SVR12 rate was 96%. By genotype, SVR12 rates were 95% (genotype 1), 100% (genotype 2), 97% (genotype 3), and 100% (genotype 4). Two patients experienced virologic relapse: one with genotype 1a infection was non-cirrhotic and treatment naive, and one with genotype 3 infection was non-cirrhotic and treatment experienced. One patient discontinued SOF/VEL due to hyperglycemia. No serious or severe adverse events were deemed SOF/VEL-related by the investigator, and no liver transplant rejection episodes or deaths occurred during the study period. Conclusions Treatment with SOF/VEL for 12 weeks was highly effective and well tolerated in genotype 1–4 HCV-infected liver transplant recipients with and without cirrhosis. Lay summary Sofosbuvir/Velpatasvir is a combination of two drugs in one tablet that is approved for the treatment of patients with chronic hepatitis C virus (HCV) infection. When patients with chronic HCV infection receive a liver transplant, the HCV infection usually recurs, and damages the transplanted liver. This study tested the effects of 12 weeks of sofosbuvir/Velpatasvir treatment in patients who had HCV recurrence after a liver transplant. Three months following the end of treatment, 96% of patients were cured of HCV infection. Clinical trial number: NCT02781571.

  • sofosbuvir Velpatasvir in patients with hepatitis c virus genotypes 1 6 and compensated cirrhosis or advanced fibrosis
    Liver International, 2018
    Co-Authors: T Asselah, John Mcnally, Diana M Brainard, S Zeuzem, Anu Osinusi, Mark S Sulkowski, Graham R Foster, Stefan Bourgeois, S Pianko, Mani G Subramanian
    Abstract:

    Background & Aims Patients with chronic hepatitis C virus (HCV) infection and advanced fibrosis (Metavir F3) or cirrhosis (Metavir F4) have been identified as a priority group for immediate treatment. We evaluated the safety and efficacy of sofosbuvir-Velpatasvir in patients with HCV genotype 1-6 infection and compensated cirrhosis or advanced fibrosis. Methods This retrospective analysis included 501 patients with compensated cirrhosis or advanced fibrosis (F3/F4), as defined by >0.59 on Fibrotest, >9.5 kPa on Fibroscan, or F3/F4 (Metavir) or F4 (Ishak) on liver biopsy. Patients received sofosbuvir-Velpatasvir for 12 weeks. Sustained virological response 12 weeks after treatment (SVR12) was determined. Results Forty-four percent of patients had cirrhosis. SVR12 was achieved by 98% of patients (490/501; 95% CI, 96%-99%). SVR12 rates were 100% for HCV genotypes 2 (85/85), 4 (60/60), 5 (13/13), and 6 (20/20). SVR12 rates were 98% (167/170) in HCV genotype 1 patients and 95% (145/153) in HCV genotype 3 patients. Among patients with cirrhosis 96% (212/220) achieved SVR12, versus 99% (278/281) for those with advanced fibrosis. SVR12 was 98% (306/311) for treatment-naive patients and 97% (184/190) for treatment-experienced patients. No patients discontinued treatment due to adverse events. Eight patients reported nine serious adverse events; none was considered related to study procedures or drugs. Conclusions Sofosbuvir plus Velpatasvir is highly effective and safe for treating patients with HCV genotypes 1, 2, 3, 4, 5, or 6 and advanced fibrosis or compensated cirrhosis. This article is protected by copyright. All rights reserved.

  • Resistance analysis in patients with genotype 1-6 HCV infection treated with sofosbuvir/Velpatasvir in the phase III studies.
    Journal of Hepatology, 2017
    Co-Authors: Christophe Hezode, John Mcnally, Brian P Doehle, Hadas Dvory-sobol, Anu Osinusi, Evguenia S. Svarovskaia, Nancy Reau, Ragavi Shanmugam, Charlotte Hedskog, Diana M Brainard
    Abstract:

    Background & Aims The fixed-dose combination of sofosbuvir/Velpatasvir was highly efficacious in patients infected with genotype (GT)1–6 hepatitis C virus (HCV) in the ASTRAL studies. This analysis evaluated the impact of baseline resistance-associated substitutions (RASs) on treatment outcome and emergence of RASs in patients infected with HCV GT1-6 who were treated with sofosbuvir/Velpatasvir. Methods Non-structural protein 5A and 5B (NS5A and NS5B ) deep sequencing was performed at baseline and at the time of relapse for all patients treated with sofosbuvir/Velpatasvir for 12 weeks (n = 1,778) in the ASTRAL-1–3, ASTRAL-5 and POLARIS-2–3 studies. Results Patients with 37 known and 19 novel HCV subtypes were included in these analyses. Overall, 28% (range 9% to 61% depending on genotype) had detectable NS5A class RASs at baseline, using a 15% sequencing assay cut-off. There was no significant effect of baseline NS5A class RASs on sustained virologic response at week 12 (SVR12) with sofosbuvir/Velpatasvir; the SVR12 rate in the presence of NS5A class RASs was 100% and 97%, in patients with GT1a and GT1b infection, respectively, and 100% in patients with GT2 and GT4–6 infections. In GT3 infection, the SVR rate was 93% and 98% in patients with and without baseline NS5A class RASs, respectively. The overall virologic failure rate was low (20/1,778 = 1.1%) in patients treated with sofosbuvir/Velpatasvir. Single NS5A class resistance was observed at virologic failure in 17 of the 20 patients. Conclusions Sofosbuvir/Velpatasvir taken for 12 weeks once daily resulted in high SVR rates in patients infected with GT1–6 HCV, irrespective of baseline NS5A RASs. NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients. Lay summary Sofosbuvir/Velpatasvir taken once daily for 12 weeks resulted in high sustained virologic response rates in patients infected with HCV, irrespective of the presence of NS5A resistance-associated variants prior to treatment. Single class NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients.

  • resistance analysis in patients with genotype 1 6 hcv infection treated with sofosbuvir Velpatasvir in the phase iii studies
    Journal of Hepatology, 2017
    Co-Authors: Christophe Hezode, John Mcnally, Brian P Doehle, Hadas Dvorysobol, Anu Osinusi, Evguenia S. Svarovskaia, Nancy Reau, Ragavi Shanmugam, Charlotte Hedskog, Diana M Brainard
    Abstract:

    Background & Aims The fixed-dose combination of sofosbuvir/Velpatasvir was highly efficacious in patients infected with genotype (GT)1–6 hepatitis C virus (HCV) in the ASTRAL studies. This analysis evaluated the impact of baseline resistance-associated substitutions (RASs) on treatment outcome and emergence of RASs in patients infected with HCV GT1-6 who were treated with sofosbuvir/Velpatasvir. Methods Non-structural protein 5A and 5B (NS5A and NS5B ) deep sequencing was performed at baseline and at the time of relapse for all patients treated with sofosbuvir/Velpatasvir for 12 weeks (n = 1,778) in the ASTRAL-1–3, ASTRAL-5 and POLARIS-2–3 studies. Results Patients with 37 known and 19 novel HCV subtypes were included in these analyses. Overall, 28% (range 9% to 61% depending on genotype) had detectable NS5A class RASs at baseline, using a 15% sequencing assay cut-off. There was no significant effect of baseline NS5A class RASs on sustained virologic response at week 12 (SVR12) with sofosbuvir/Velpatasvir; the SVR12 rate in the presence of NS5A class RASs was 100% and 97%, in patients with GT1a and GT1b infection, respectively, and 100% in patients with GT2 and GT4–6 infections. In GT3 infection, the SVR rate was 93% and 98% in patients with and without baseline NS5A class RASs, respectively. The overall virologic failure rate was low (20/1,778 = 1.1%) in patients treated with sofosbuvir/Velpatasvir. Single NS5A class resistance was observed at virologic failure in 17 of the 20 patients. Conclusions Sofosbuvir/Velpatasvir taken for 12 weeks once daily resulted in high SVR rates in patients infected with GT1–6 HCV, irrespective of baseline NS5A RASs. NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients. Lay summary Sofosbuvir/Velpatasvir taken once daily for 12 weeks resulted in high sustained virologic response rates in patients infected with HCV, irrespective of the presence of NS5A resistance-associated variants prior to treatment. Single class NS5A inhibitor resistance, but not sofosbuvir resistance, was detected in the few patients with virologic failure. These data highlight the high barrier to resistance of this regimen for the treatment of chronic HCV across all genotypes in the vast majority of patients.

Gregory T Everson - One of the best experts on this subject based on the ideXlab platform.

  • sofosbuvir and Velpatasvir for the treatment of hepatitis c
    Expert Review of Gastroenterology & Hepatology, 2017
    Co-Authors: Whitney E Jackson, Gregory T Everson
    Abstract:

    ABSTRACTIntroduction: Direct acting antivirals are revolutionizing the treatment of chronic hepatitis C. Specifically, the combination therapy sofosbuvir and Velpatasvir offers a pangenotypic regimen with high sustained viral response (SVR).Areas covered: Reviewed here are the clinical trials that led to the FDA approval of sofosbuvir and Velpatasvir combination therapy, the adverse events during registration trials, and drug-drug interactions. Sofosbuvir and Velpatasvir is a fixed dose regimen that is both interferon- and ribavirin-free. It is administered for 12 weeks as a once-a-day pill, covers all genotypes of hepatitis C, and achieves SVR >95% in non-cirrhotic patients and patients with compensated cirrhosis. Addition of ribavirin is recommended for patients with decompensated cirrhosis (CTP B or C). Baseline resistance-associated substitutions do not appear to impair ability to achieve SVR with an initial course of treatment.Expert commentary: Availability of this highly efficacious, well tolerated...

  • efficacy of sofosbuvir Velpatasvir and gs 9857 in patients with hepatitis c virus genotype 2 3 4 or 6 infections in an open label phase 2 trial
    Gastroenterology, 2016
    Co-Authors: Edward Gane, Gregory T Everson, M Davis, Kyle Etzkorn, Stuart C Gordon, Catherine A M Stedman, Kris V Kowdley, David Pound, David Bernstein, Maribel Rodrigueztorres
    Abstract:

    Background & Aims Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor Velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. Methods We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naive and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-Velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6–12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). Results After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naive patients without cirrhosis (29 of 33; 95% confidence interval, 72%–97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naive patients with cirrhosis (28 of 30; 95% CI, 78%–99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%–100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%–100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. Conclusions In a phase 2 open-label trial, we found sofosbuvir-Velpatasvir plus GS-9857 (8 weeks in treatment-naive patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.

  • sofosbuvir with Velpatasvir in treatment naive noncirrhotic patients with genotype 1 to 6 hepatitis c virus infection a randomized trial
    Annals of Internal Medicine, 2015
    Co-Authors: Gregory T Everson, William J Towner, M Davis, David L Wyles, Ronald Nahass, Paul J Thuluvath, Kyle Etzkorn, Federico Hinestrosa, Myron J Tong, Mordechai Rabinovitz
    Abstract:

    BACKGROUND: Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. OBJECTIVE: To assess the safety and efficacy of sofosbuvir with Velpatasvir in patients infected with HCV genotypes 1 to 6. DESIGN: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766). SETTING: 48 U.S. sites. PATIENTS: 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with Velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and Velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. MEASUREMENTS: Sustained virologic response at 12 weeks (SVR12). RESULTS: In part A, SVR12 rates were 96% (26 of 27) with Velpatasvir, 25 mg, and 100% (28 of 28) with Velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with Velpatasvir, 25 mg, and 95% (21 of 22) with Velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with Velpatasvir, 25 mg; 83% (25 of 30) with Velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with Velpatasvir, 100 mg; and 81% (25 of 31) with Velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with Velpatasvir, 25 mg; 88% (22 of 25) with Velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with Velpatasvir, 100 mg; and 88% (23 of 26) with Velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide. LIMITATION: The study was open-label, no inferential statistics were planned, and sample sizes were small. CONCLUSION: Twelve weeks of sofosbuvir, 400 mg, and Velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6. PRIMARY FUNDING SOURCE: Gilead Sciences.

  • sofosbuvir with Velpatasvir in treatment naive noncirrhotic patients with genotype 1 to 6 hepatitis c virus infection
    Annals of Internal Medicine, 2015
    Co-Authors: Gregory T Everson, William J Towner, M Davis, David L Wyles, Ronald Nahass, Paul J Thuluvath, Kyle Etzkorn, Federico Hinestrosa, Myron J Tong, Mordechai Rabinovitz
    Abstract:

    Pangenotypic treatments for HCV infection would be useful worldwide. In a phase 2 trial, treatment with sofosbuvir plus Velpatasvir resulted in high sustained virologic response at 12 weeks in pati...

M Davis - One of the best experts on this subject based on the ideXlab platform.

  • deferred treatment with a fixed dose combination of sofosbuvir Velpatasvir for chronic hepatitis c virus genotype 1 2 4 and 6 infection
    Journal of Viral Hepatitis, 2019
    Co-Authors: T Asselah, M Davis, Bernard Willems, Stephen D Shafran, Evguenia S. Svarovskaia, Stefan Bourgeois, Philippe Mathurin, Mindie H Nguyen, K C Huang, Anu Osinusi
    Abstract:

    Sofosbuvir-Velpatasvir is approved for the treatment of chronic hepatitis C virus (HCV) infection. In this single-arm, open-label, phase 3, deferred treatment study, we investigated the efficacy and safety of sofosbuvir-Velpatasvir among patients randomized to the placebo group in the ASTRAL-1 study. Patients received sofosbuvir-Velpatasvir (400/100 mg) once daily for 12 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response 12 weeks after the end of therapy (SVR12). The primary safety endpoint was any adverse events (AEs) leading to the permanent discontinuation of study drug. Overall, 108/111 (97%, 95% confidence interval [CI], 92%-99%) achieved SVR12, and only one patient had virological failure. SVR12 was achieved by 61/63 (97%, 95%CI, 89%-100%) genotype 1 patients, 20/20 (100%; 95%CI, 83%-100%) with genotype 2, 19/19 (100%; 95%CI, 82%-100%) with genotype 4 and 8/9 (89%; 95% CI, 52%-100%) with genotype 6. All (19/19; 95%CI, 82-100) patients with cirrhosis and all (31/31, 95%CI, 89-100) with prior treatment experience achieved SVR12. The safety profile during treatment was similar to that observed in patients receiving placebo treatment. The most common AEs were headache, fatigue and nausea. One patient (1%) discontinued treatment due to an AE of gallbladder carcinoma, which was not considered related to treatment. Of five reported serious AEs, none were considered related to study drug. Sofosbuvir-Velpatasvir for 12 weeks was effective and well tolerated among untreated and previously treated patients with HCV genotype 1, 2, 4 or 6 infection, including those with compensated cirrhosis (ClinicalTrials.gov NCT02346721).

  • sofosbuvir Velpatasvir with ribavirin for 24 weeks in hepatitis c virus patients previously treated with a direct acting antiviral regimen
    Hepatology, 2017
    Co-Authors: Edward Gane, M Davis, Kyle Etzkorn, Federico Hinestrosa, Mitchell L Shiffman, Hadas Dvorysobol, K C Huang, Giuseppe Morelli, Catherine A M Stedman, Anu Osinusi
    Abstract:

    : The optimal retreatment strategy for patients chronically infected with hepatitis C virus who experience virologic failure after treatment with direct-acting antiviral-based therapies remains unclear. In this multicenter, open-label, phase 2 study, we evaluated the efficacy and safety of a fixed-dose combination of sofosbuvir-Velpatasvir (400 mg/100 mg) plus weight-adjusted ribavirin administered for 24 weeks in patients who did not achieve sustained virologic response after prior treatment with direct-acting antiviral regimens that included the nucleotide analogue nonstructural protein 5B inhibitor sofosbuvir plus the nonstructural protein 5A inhibitor Velpatasvir with or without the nonstructural protein 3/4A protease inhibitor voxilaprevir. The primary efficacy endpoint was the proportion of patients achieving sustained virologic response at 12 weeks after the cessation of treatment. In total, 63 of 69 (91%; 95% confidence interval, 82%-97%) patients achieved sustained virologic response at 12 weeks, including 36 of 37 (97%; 95% confidence interval, 86%-100%) patients with hepatitis C virus genotype 1 infection, 13 of 14 (93%; 95% confidence interval, 66%-100%) patients with genotype 2 infection, and 14 of 18 (78%; 95% confidence interval, 52%-94%) patients with genotype 3 infection. Most adverse events were of mild or moderate severity. The most frequently reported adverse events were fatigue, nausea, headache, insomnia, and rash. One patient (1%) with genotype 1a infection discontinued all study drugs due to an adverse event (irritability). CONCLUSION: Retreatment of patients who previously failed direct-acting antiviral-based therapies with sofosbuvir-Velpatasvir plus ribavirin for 24 weeks was well tolerated and effective, particularly those with hepatitis C virus genotype 1 or 2 infection. (Hepatology 2017;66:1083-1089).

  • efficacy of sofosbuvir Velpatasvir and gs 9857 in patients with hepatitis c virus genotype 2 3 4 or 6 infections in an open label phase 2 trial
    Gastroenterology, 2016
    Co-Authors: Edward Gane, Gregory T Everson, M Davis, Kyle Etzkorn, Stuart C Gordon, Catherine A M Stedman, Kris V Kowdley, David Pound, David Bernstein, Maribel Rodrigueztorres
    Abstract:

    Background & Aims Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor Velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. Methods We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naive and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-Velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6–12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). Results After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naive patients without cirrhosis (29 of 33; 95% confidence interval, 72%–97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naive patients with cirrhosis (28 of 30; 95% CI, 78%–99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%–100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%–100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. Conclusions In a phase 2 open-label trial, we found sofosbuvir-Velpatasvir plus GS-9857 (8 weeks in treatment-naive patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.

  • sofosbuvir with Velpatasvir in treatment naive noncirrhotic patients with genotype 1 to 6 hepatitis c virus infection a randomized trial
    Annals of Internal Medicine, 2015
    Co-Authors: Gregory T Everson, William J Towner, M Davis, David L Wyles, Ronald Nahass, Paul J Thuluvath, Kyle Etzkorn, Federico Hinestrosa, Myron J Tong, Mordechai Rabinovitz
    Abstract:

    BACKGROUND: Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. OBJECTIVE: To assess the safety and efficacy of sofosbuvir with Velpatasvir in patients infected with HCV genotypes 1 to 6. DESIGN: Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766). SETTING: 48 U.S. sites. PATIENTS: 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with Velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and Velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. MEASUREMENTS: Sustained virologic response at 12 weeks (SVR12). RESULTS: In part A, SVR12 rates were 96% (26 of 27) with Velpatasvir, 25 mg, and 100% (28 of 28) with Velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with Velpatasvir, 25 mg, and 95% (21 of 22) with Velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In part B, for genotype 1, SVR12 rates were 87% (26 of 30) with Velpatasvir, 25 mg; 83% (25 of 30) with Velpatasvir, 25 mg, plus ribavirin; 90% (26 of 29) with Velpatasvir, 100 mg; and 81% (25 of 31) with Velpatasvir, 100 mg, plus ribavirin. For genotype 2, SVR12 rates were 77% (20 of 26) with Velpatasvir, 25 mg; 88% (22 of 25) with Velpatasvir, 25 mg, plus ribavirin; 88% (23 of 26) with Velpatasvir, 100 mg; and 88% (23 of 26) with Velpatasvir, 100 mg, plus ribavirin. Adverse events included fatigue (21%), headache (20%), and nausea (12%). One patient committed suicide. LIMITATION: The study was open-label, no inferential statistics were planned, and sample sizes were small. CONCLUSION: Twelve weeks of sofosbuvir, 400 mg, and Velpatasvir, 100 mg, was well-tolerated and resulted in high SVR in patients infected with HCV genotypes 1 to 6. PRIMARY FUNDING SOURCE: Gilead Sciences.

  • sofosbuvir with Velpatasvir in treatment naive noncirrhotic patients with genotype 1 to 6 hepatitis c virus infection
    Annals of Internal Medicine, 2015
    Co-Authors: Gregory T Everson, William J Towner, M Davis, David L Wyles, Ronald Nahass, Paul J Thuluvath, Kyle Etzkorn, Federico Hinestrosa, Myron J Tong, Mordechai Rabinovitz
    Abstract:

    Pangenotypic treatments for HCV infection would be useful worldwide. In a phase 2 trial, treatment with sofosbuvir plus Velpatasvir resulted in high sustained virologic response at 12 weeks in pati...