Velpatasvir Research Articles

Upcoming direct acting antivirals for hepatitis C patients with a prior treatment failure.

Despite the high efficacy of direct acting antivirals (DAAs) not all patients successfully clear hepatitis C virus infection, in fact, approximately 1–3% fail to reach a sustained virological response 12 weeks after end of treatment. DAA failures are characterized by advanced liver disease, specific genotypes/subtypes and resistance associated substitutions to the DAA class they have been treated with. Current European Association for the Study of the Liver guidelines recommend three therapeutic options for such patients. The first is a 12 week course of sofosbuvir (SOF), velpatasvir (VEL) and voxilaprevir (VOX), which has shown to be effective in 90–99% of patients and was granted A1 level recommendation. The second option, reserved for patients who have predictors of failure consists in 12 weeks regimen with glecaprevir (GLE) and pibrentasvir (PIB), effective in 90–97%. Finally, although not supported by published data, for especially difficult to treat patients there should theoretically be a benefit in prolonged combinations of SOF+GLE/PIB or SOF/VEL/VOX±ribavirin. This review presents the latest evidence from both clinical trials and real-life on such therapeutic strategies.

A Novel Stress Indicating RP-HPLC Method Development and Validation for the Simultaneous Estimation of Velpatasvir and Sofosbuvir in Bulk and Its Tablet Dosage Form

Aim: The objective of the study was simplest, accurate, precise and robust reversed phase high performance liquid chromatographic (RP-HPLC) method was developed for the estimation of Velpatasvir (VEL) and Sofosbuvir (SOF) in the bulk and its tablet dosage form.
 Study Design: The Quantitative and Qualitative estimation and designed forced degradation study of Velpatasvir & Sofosbuvir by RP-HPLC.
 Place and Duration of Study: The study was carried at Santhiram College of Pharmacy and time taken 4 months.
 Method: The method was attained by used Waters( 5µm, C18 250 x 4.6 mm) column with mobile phase consists of 0.5 mM disodium hydrogen phosphate buffer pH adjusted to 6.5, with Orthophosphoric acid and Methanol in the ratio of 78:22 v/v, a flow rate of 1.0 mL/min and ultraviolet detection at 285 nm.
 Results: The method was validated as per ICH guidelines with different parameters, the mean retention times of VEL and SOF were found to be 2.8 & 4.7 min respectively. The resolution between VEL and SOF was found to be 10.66. The Correlation coefficients for calibration curves within the detection range of 32.5 - 97.5 and 125 - 375 µg/mL were 0.999 for VEL and SOF respectively. The LOD and LOQ for VEL and SOF were found to be 0.0068-0.029 µg/mL and 0.104-0.342 µg/mL respectively.
 Conclusion: The results were indicated that the developed method was used for the routine analysis of VEL & SOF combined form in bulk and its commercial formulation. To the best of our knowledge, there was no method of RP-HPLC for the determination of VEL alone or in combination with SOF molecule.

Novel determination of a new antiviral combination; sofosbuvir and velpatasvir by high performance thin layer chromatographic method; application to real human samples

Sofosbuvir (SOF) and velpatasvir (VEL) represent a brand new antiviral combination. A novel, simple and economical high performance thin layer chromatographic separation coupled with densitometric quantification was designed for the pharmaceutical and biomedical analysis of SOF and VEL. Simultaneous quantitation of the studied drugs in their newly introduced pharmaceutical formulation and human plasma; using ledipasvir (LED) as an internal standard; was achieved. Protein precipitation technique using acetonitrile was adopted, utilizing HPTLC as a clean-up step. Separation was achieved on HPTLC silica gel 60 F254 aluminum plates with a green developing system consisting of ethyl acetate-isopropanol (90:10, v/v). Densitometric scanning was carried out at 260 and 302 nm for SOF and VEL, respectively. Peak purity was evaluated through the winCATS® software spectral correlation method to ascertain the specificity of the proposed method. Method validation was assessed as per the US-FDA guidelines. The proposed method represents a simple, green and cost-effective alternative to the only existing more complicated reported LC-MS/MS technique. The method would afford a competent tool for therapeutic drug monitoring and bioavailability studies of SOF and VEL. The method could be applied to the quality control and routine analysis of SOF and VEL in their pure forms and pharmaceutical formulations. Furthermore, the application was extended to simultaneous quantitation of SOF and VEL in real human plasma.

Quantification of second generation direct-acting antivirals daclatasvir, elbasvir, grazoprevir, ledipasvir, simeprevir, sofosbuvir and velpatasvir in human plasma by UPLC-MS/MS

Direct-acting antivirals (DAA) have markedly improved the treatment of hepatitis C, with a series of DAA combinations available for treatment. A sensitive method by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the simultaneous quantification of seven commonly used DAAs, daclatasvir (DAC), elbasvir (ELB), grazoprevir (GZR), ledipasvir (LDV), simeprevir (SIM), sofosbuvir (SOF), velpatasvir (VEL) and the primary analyte of interest of SOF (GS-331007) in EDTA plasma.Adequate chromatographic separation with well-defined peaks for all eight analytes was achieved with an Acquity UPLC BEH C18 column (1.7 μm 2.1 × 50 mm). Runtime for the final assay was 12 min. Protein precipitation in the sample preparation and stable isotope- labelled internal standards resulted in a robust sensitive and rapid method.Method validation was performed in accordance with the “guideline on bioanalytical method validation” of the European Medicines Agency (EMA). No interferences from endogenous substances were observed and carry-over in the blank sample was <20% of the LLOQ of each analyte and <5% of the IS after injection of the HLOQ sample. Validation was established over the range of 10–5000 μg/L for DAC and SIM, 3.0–1500 μg/L for ELB and GZR, 7.5–1500 μg/L for LDV and VEL, 5.0–2500 μg/L for SOF and 25–5000 μg/L for GS-331007. Within-day accuracy values for all analytes, ranged from 94% to 109%, and precision expressed as residual standard deviation % (RSD) was <9.3%. Between-day accuracy ranged from 99 to 107% with a RSD of <5.3%. For the lower limit of quantification, the percent deviation from the nominal concentration and the relative standard deviation was <20%.The method has been applied successfully in clinical evaluation of patients treated with DAA and to describe the pharmacokinetics of DAAs in clinical studies.

Spectrophotometric assessment of the brand new antiviral combination: Sofosbuvir and velpatasvir in their pure forms and pharmaceutical formulation.

Sofosbuvir (SOF) and velpatasvir (VEL) are recently co-formulated together for the treatment of hepatitis C virus. Smart and robust spectrophotometric methods were first developed and validated for quantification of SOF and VEL in their pure forms and in their combined pharmaceutical formulation without preliminary separation. VEL has two UV maxima at 302.5 and 337.0 nm that allow its direct determination by zero-order spectrophotometric method (D°) without any interference from SOF in a linear range of 2.0-30.0 μg/mL. On the other hand, determination of SOF in presence of VEL was carried out by four smart spectrophotometric methods, developed for resolving the overlaid spectra of these binary mixture. These methods are dual wavelength (DW), ratio subtraction (RS), ratio difference (RD) and first derivative of ratio spectra method (1DD). Linearity was checked and found to be in the range of 5.0-90.0 μg/mL for SOF by all of the aforementioned spectrophotometric methods. The developed methods were optimized and validated in accordance to the ICH guidelines. They were successfully utilized for estimating both SOF and VEL in their pure forms, laboratory prepared mixtures and in their pharmaceutical formulations with good recoveries. The methods can be easily applied for the routine analysis in quality control laboratories.

Efficacy of 12-weeks velpatasvir plus sofosbuvir-based regimen in HCV-naive subjects with mild fibrosis: a meta-analysis.

Background and aims:In literature systematic data on treatment with the fixed-dose combination of sofosbuvir and velpatasvir for 12 weeks in anti-HCV/HCV RNA positive subjects with mild fibrosis and naïve to previous Interferon free regimen are scanty. A meta-analysis has been performed to evaluate the efficacy of velpatasvir plus sofosbuvir combination in these patients.Methods:All randomized or non-randomized studies, investigating the sustained virological response rate to sofosbuvir plus velpatasvir without ribavirin for 12 weeks in subjects naïve to previous DAA therapy and with fibrosis F0-F2 or F0-F3, were included in the meta-analysis.Results:A total of 16 studies enrolling 4,907 subjects met the inclusion criteria and were included in this meta-analysis. The prevalence of SVR by sofosbuvir and velpatasvir was 98% (95% CI 96-99%) in the 4,907 subjects without cirrhosis. The prevalence of SVR was similar considering the 9clinical studies and the 7 real-world studies (98%, CI 95%: 96-99% and 98%; CI 95%: 96-99%, respectively). Considering the 4 studies enrolling 1,371 subjects without advanced liver fibrosis the prevalence of SVR was also high [96% (95% CI: 94-98%)]. Data indicate a prevalence of SVR ranging to 95-100% according to the different HCV genotypes.Conclusion:Sofosbuvir plus velpatasvir therapeutic regimen was highly effective in HCV patients without advanced liver disease naïve to previous DAA regimen independently the different HCV genotypes. (www.actabiomedica.it)

Safety and efficacy of sofosbuvir-based direct-acting antiviral regimens for hepatitis C virus genotype 6 in Southwest China: Real-world experience of a retrospective study.

Optional treatments for patients with chronic hepatitis C virus (HCV) genotype (GT) 6 infection have not been extensively studied. This study aimed to evaluate the safety and efficacy of sofosbuvir (SOF)-based direct-acting antiviral agents (DAAs) for HCV GT6. We performed a retrospective study at the West China Hospital of Sichuan University in Southwest China from January 2016 to May 2017. Our study screened 130 treatment-naïve patients with chronic HCV GT6 and without liver cirrhosis. A total of 60 HCV GT6 patients were ultimately enrolled. All patients received SOF-based DAAs therapy, including SOF 400mg plus daclatasvir (DCV) 60mg daily or SOF 400mg plus velpatasvir (VEL) 100mg daily for 12weeks. The sustained virological response 12weeks after treatment (SVR12) was 100% (60/60) in treatment-naïve patients with HCV GT6, including 100% (37/37) of patients receiving SOF plus DCV therapy and 100% (23/23) of patients receiving SOF plus VEL therapy. Measurements of liver stiffness were significantly decreased in patients at week 12 (P=0.014) and week 24 (P<0.001) of DAAs treatment compared to baseline values. The serum biomarker aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score were also significantly reduced at week 12 and week 24 compared to before treatment (both P<0.001). SOF-based therapy was well-tolerated, and no serious adverse events were reported. In conclusion, SOF plus DCV and SOF plus VEL were safe and achieved a high SVR12 rate for treatment-naïve patients with HCV GT6 without liver cirrhosis.

Generic sofosbuvir-based interferon-free direct acting antiviral agents for patients with chronic hepatitis C virus infection: a real-world multicenter observational study

Real-world data regarding the effectiveness and safety of generic sofosbuvir (SOF)-based interferon-free direct acting antiviral agents (DAAs) for patients with chronic hepatitis C virus (HCV) infection remain limited. A total of 517 chronic HCV-infected patients receiving 12 or 24 weeks of SOF-based therapies were retrospectively enrolled in 4 academic centers in Taiwan. The rate of sustained virologic response at week 12 off-therapy (SVR12) and that of treatment completion were assessed. The baseline characteristics and on-treatment HCV viral kinetics to predict SVR12 were analyzed. By evaluable population (EP) analysis, the SVR12 rate was 95.4% (95% confidence interval [CI]: 93.2–96.9%). The SVR12 was achieved in 29 of 34 patients (85.3%, 95% CI: 69.6–93.6%), 130 of 139 patients (93.5%, 95% CI: 88.2–96.6%), 119 of 124 patients (96.0%, 95% CI: 90.9–98.3%) and 215 of 220 patients (97.7%, 95% CI: 94.8–99.0%) who received SOF in combination with ribavirin (RBV), ledipasvir (LDV), daclatasvir (DCV) and velpatasvir (VEL), respectively. Of 517 patients, 514 (99.4%) completed the scheduled treatment. All 15 patients with true virologic failures were relapsers. Two decompensated cirrhotic patients had on-treatment deaths which were not related to DAAs. All 7 patients who were lost to follow-up had undetectable HCV RNA level at the last visit. The SVR12 rates were comparable in terms of baseline patient characteristics and viral decline at week 4 of treatment. In conclusion, generic SOF-based regimens are well tolerated and provide high SVR12 rates in patients with chronic HCV infection.

Novel determination of sofosbuvir and velpatasvir in human plasma by UPLC-MS/MS method: Application to a bioequivalence study.

A novel and sensitive LC-MS/MS method was developed, optimized and validated for quantification of sofosbuvir (SOF) and velpatasvir (VEL) in human plasma using ledipasvir as an internal standard (IS). Sample preparation was done using acetonitrile for precipitation of plasma proteins. Chromatographic analysis was done on an Acquity UPLC BEH C18 column using 0.1% formic acid and acetonitrile as a mobile phase. The Xevo TQD LC-MS/MS system was run with electrospray ionization mode. The developed method was optimized and then validated according to the US Food and Drug Administration guidelines. Linearity was found to be in the range of 0.25-3500 ng/mL for SOF and 1-1000 ng/mL for VEL. A short run time of 1.5 min allows swift analysis of many plasma samples per day. The developed method was successfully utilized for estimating both SOF and VEL in the plasma of healthy human volunteers participated in a bioequivalence study.

A novel molecularly imprinted sensing platform based on MWCNTs/AuNPs decorated 3D starfish like hollow nickel skeleton as a highly conductive nanocomposite for selective and ultrasensitive analysis of a novel pan-genotypic inhibitor velpatasvir in body fluids

Herein, a novel ultrasensitive molecularly imprinted sensor (MIS) for selective determination of a new direct acting anti-HCV velpatasvir (VELPR) was developed and fabricated for the first time. The fabricated MIS based on modification of a glassy carbon electrode (GCE) with multi-walled carbon nanotubes-gold nanoparticles (MWCNTs-AuNPs) composite after deposition on electro-synthesized 3D starfish like hollow nickel skeleton (3D SH-Ni S) to increase conductivity and effective surface area of MIS to amplify its signal. After that, the electrode was coated with molecularly imprinted polymer (MIP) by in situ electro-polymerization forming cavity with specific affinity and natural binding sites to VELPR. Differential pulse voltammetry (DPV) was used for selective detection of VELPR in complex matrices whereas, scanning electron microscope (SEM) and cyclic voltammetry (CV) were employed to characterize the fabricated sensor. All experimental factors concerning fabrication and chemical sensing properties were carefully studied and optimized. Under the optimized variables, the fabricated sensor exhibited excellent DPV response to VELPR over the range of 0.649–80.0 ng mL−1 with LOD of 0.21 ng mL−1. In addition to high sensitivity and selectivity, the sensor response to VELPR was highly reproducible and stable. Moreover, the fabricated sensor was successfully applied for the determination of VELPR in complex biological matrices and pharmaceutical tablets.

Real life rates of sustained virological response (SVR) and predictors of relapse following DAA treatment in genotype 3 (GT3) patients with advanced fibrosis/cirrhosis.

BackgroundTreatment of GT3 remains challenging compared to other genotypes.AimsTo explore real life SVR rates and to identify predictors of virological failure across the most recently used Direct acting antiviral (DAA) regimens in a large cohort of Italian patients with cirrhosis or advanced fibrosis (F3 or F4).MethodsBetween May 2015 and June 2017, the combinations of sofosbuvir (SOF) plus daclatasvir (DCV) ± RBV and SOF plus velpatasvir (VEL) ± RBV become available in our Country. Patients were treated following Italian guidelines within a protocol implemented by 11 centers working together on genetics.ResultsOf 336 patients, 38.1% were Peg/IFN-experienced. SOF/DCV was used in 65.1%, SOF/VEL in the remaining. Overall SVR12 was 90.2% ranging from 87.2% after SOF/DCV to 95.7% after SOF/VEL (p = 0.012). No additional benefits of RBV use were observed for both regimens. 155 patients (46.1%) had cirrhosis. SVR12 was 87.1% (135/155) for cirrhotic patients and 92.8% (169/182) for non-cirrhotic (p = 0.09). NS5A-RASs were present at baseline in 6.4% of patients, PNPLA3GG and IL28BCC genotypes in 7.3% and 33.0%, respectively. No association between favorable genetics and SVR12 was observed. Predictors of relapse were: history of Peg/IFN/RBV failure (OR = 6.34, 95% CI 2.04–19.66, P = .001), baseline NS5A-RASs (OR = 8.7, 95% CI 1.58–47.92, P = 0.013) and treatment regimen (OR = 5.57 95% CI 1.64–18.95.96, P = 0.006).ConclusionsOur real-world results validate the efficacy of current GT3 IFN-free regimens suggesting that, among patients with severe disease, Peg/IFN/RBV experience and NS5A associated RASs are predictors of relapse. Their relevance can be expected to decline with the use of SOF/VEL. (250).

Selective and sensitive spectrofluorimetric quantification of velpatasvir in presence of sofosbuvir. Application to their co-formulated tablet.

A new sensitive, rapid and simple spectrofluorimetric method was utilized for the assessment of velpatasvir (VPS) in its bulk form as well as in its combined tablet with sofosbovir (SFV). The technique relies on measuring the native fluorescence of VPS in methanol at 385 nm and 400 nm after excitation at 295 nm. The fluorescence–concentration plots were rectilinear through the range of 2.0–20.0 ng mL−1 at both emission maxima with lower detection limits of 0.146 ng mL−1 and 0.378 ng mL−1, and lower quantification limits of 0.444 ng mL−1 and 1.147 ng mL−1 at 385 nm and 400 nm, respectively. The proposed method was appropriately used for the analysis of VPS in its commercial tablet formulation and the results were in good agreement with those achieved with the applied comparison method.

Resistance characterization of ledipasvir and velpatasvir in hepatitis C virus genotype 4

HCV genotype 4 (GT4) has often been overlooked in drug development, even though it infects ~20 million people worldwide. Ledipasvir/sofosbuvir and sofosbuvir/velpatasvir were highly efficacious in GT4 HCV-infected patients from GS-US-337-1119 and GS-US-342-1138. Here, we characterize the resistance profile of ledipasvir (LDV) and velpatasvir (VEL) in patients with GT4 HCV infection. NS5A deep-sequencing was performed for 454 patients infected with HCV GT4 at baseline, including 44 patients enrolled in GS-US-337-1119 and 116 patients enrolled in GS-US-342-1138, and at relapse for patients with virologic failure. LDV and VEL susceptibilities of 56 patient isolates were determined. In GS-US-337-1119, SVR12 rates were 100% for all subtypes except 4b and 4r. Phenotypic assessment of 56 HCV NS5A patient isolates from various GT4 subtypes indicated that LDV had high potency for the common subtypes 4a/d, and subtypes 4c/f/k/l/m/n/o/p/r/t despite the presence of resistance-associated substitutions (RASs). For the rare GT4b, LDV median EC50 was higher, but with a broad range of individual values. Importantly, all GT4b isolates tested had 2-4 NS5A RASs, some including Y93H. Similarly, the 2 GT4r infected patients who had virologic relapse had rare triple RASs. Reversion of these substitutions to the consensus residue significantly increased LDV susceptibility. In GS-US-342-1138, all patients achieved SVR12, regardless of their subtype or presence of RASs. In vitro data confirmed that VEL is potent against all GT4 isolates tested. LDV and VEL are potent antiviral drugs, estimated to be effective against >95% and >99%, respectively, of GT4 HCV isolates.

A Highly Effective 8-Week, Single-Pill Regimen for Chronic Hepatitis C Infection

Recent phase II studies showed the safety and efficacy of triple therapy with sofosbuvir (SOF; an NS5B inhibitor), velpatasvir (VEL; a

Pharmacokinetic drug evaluation of velpatasvir plus sofosbuvir for the treatment of hepatitis C virus infection

ABSTRACTIntroduction: The fixed-dose combination therapy of sofosbuvir (SOF) plus velpatasvir (VEL) is the first pangenotypic, direct-acting antiviral (DAA), single-treatment regimen (STR) for the treatment of hepatitis C virus (HCV) infection to be commercialized. It is approved for the treatment of HCV genotypes 1, 2, 3, 4, 5, and 6. Following approval in 2016, new pharmacokinetic and pharmacodynamic data were reported, which led to important clinical applications.Areas covered: This review provides a summary of the pharmacokinetics, pharmacodynamics, efficacy and safety of SOF/VEL therapy for treatment of HCV infection. The topics covered include data regarding the drug’s absorption, distribution, metabolism, excretion and antiviral activity strategies, such as clinical dose selection and treatment duration.Expert opinion: This novel combination therapy containing 400 mg of SOF plus 100 mg of VEL, taken orally, once daily, with or without food, has an excellent pharmacokinetic and pharmacodynamic profile. SOF/VEL achieved very high rates of sustained virological response in treatment-naive and treatment-experienced patients with chronic HCV genotype 1–6 infection, including those with compensated cirrhosis or HIV-1 co-infection.

Retreatment of Chronic HCV Infection after Second Generation DAA Failure in Patients in the NJ VA Healthcare System

Background The data on retreatment of patients with second-generation DAA treatment failure is limited. AASLD retreatment guidelines were established but are classified as class IIb/Level C. We analyzed treatment outcomes in NJ VA patients with prior second-generation DAA failure over a period of 1 year.Methods We performed a retrospective health record review of all HCV patients treated between May 1, 2016 and May 1, 2017. HCV genotypes (GT), the presence of cirrhosis and HIV, DAA type, and RAVs post treatment were evaluated in the treatment failure (TF) group, defined as an inability to achieve the sustained virological response 12 weeks post therapy (SVR12). These patients were retreated with a new DAA regimen selected for their individual characteristics, GT and presence of RAVs and retreatment success rates were recorded.ResultsOf 312 HCV patients, 10 failed second-generation DAA therapy during the outlined period. The TF group had 2 patients with HIV, 5 with cirrhosis, 6 with GT 1a, 2 with GT 1b, and 2 with GT 3a. Patients with GT 1a/b were initially treated with Ledipasvir/Sofosbuvir (LDV/SOF) ± Ribavirin (RBV). One patient with GT 3a was treated with LDV/SOF +RBV, and 1 with SOF+RBV. Three patients stopped treatment early due to side effects or non-compliance. Post-treatment resistance panel was available for 7/10 patients with the following detected mutations: Q30H/K/E/R, L31 L/M, Q20Q, M28V, Q80K, Y93A/H. 2/8 GT1a/b patients were re-treated with SOF/Elbasvir(EBR)/Grazoprevir(GZR)/RBV, 2 with SOF/ Velpatasvir (VEL)/RBV, 2 with EBR/GZR+/-RBV, and 2 with Viekira/SOF/RBV. 1 patient with GT 3a was retreated with SOF/Daclatasvir (DAC), 1 with SOF/VEL/RBV. All 10 patients had an undetectable viral load (VL) at the end of treatment. SVR12 has been achieved for all 5 patients that were tested, with the remaining 5 awaiting week 12.Conclusion The HCV second-generation DAA treatment failure rate in patients at the NJ VAHCS over 1 year was 3.2%. Analysis of available data indicates that the presence of RAVs might be the major cause of treatment failure among HCV patients treated with DAAs in NJ VA. Different retreatment regimens were used for a period of 12–24 weeks with 100% undetectable VL at end of treatment.Disclosures All authors: No reported disclosures.

SAT-275 - Does Sofosbuvir (SOF)/Velpatasvir (VEL) with or without Ribavirin (RBV) change the landscape of therapy in chronic hepatitis C genotype 3 (GT 3) infection? – Results from the GErman hepatitis C COhort (GECCO)

SAT-275 - Does Sofosbuvir (SOF)/Velpatasvir (VEL) with or without Ribavirin (RBV) change the landscape of therapy in chronic hepatitis C genotype 3 (GT 3) infection? – Results from the GErman hepatitis C COhort (GECCO)

Velpatasvir and sofosbuvir: How will we use a new drug when the old agents work well?

Velpatasvir and sofosbuvir: How will we use a new drug when the old agents work well?

Sofosbuvir/velpatasvir improves patient-reported outcomes in HCV patients: Results from ASTRAL-1 placebo-controlled trial

The new pan-genotypic regimen [sofosbuvir (SOF) and velpatasvir (VEL)] for hepatitis C virus (HCV) has been associated with high efficacy. The aim of this study was to assess patient-reported outcomes (PROs) of this regimen. The PRO data (CLDQ-HCV, SF-36, FACIT-F, WPAI) came from the ASTRAL-1 study, a multicenter multinational blinded placebo-controlled phase 3 clinical trial of a fixed dose combination of SOF 400mg and VEL 100mg for patients with genotype 1, 2, 4, 5, and 6 compared to placebo for 12weeks. 624 patients received active treatment [618 achieved sustained virologic response (SVR)], and 116 received placebo. The baseline PRO scores were similar. By treatment week 4, patients receiving SOF/VEL experienced improvements in general health (on average, +2.3points), emotional well-being (+3.4), FACIT-F (+1.3), and all domains of CLDQ-HCV (+2.1 to +7.3) (all p<0.005). On the other hand, the only PRO that improved in patients receiving placebo was the worry domain of CLDQ-HCV: +4.6 (p=0.002). By the end of treatment, improvement in PRO scores with SOF/VEL continued, and no improvement was noted in the placebo. Improvement in PROs were also noted 12 and 24weeks post-treatment: +3.7, on average, in patients with SVR-12 after SOF/VEL vs. -2.6, on average, in the placebo arm (p<0.005). Multivariate analysis showed that treatment-emergent changes in PROs were predicted by receiving SOF/VEL for some summary PRO score (p<0.005). This placebo-controlled trial shows that patients treated with SOF/VEL experience significant improvement of their PROs during treatment and after achieving SVR. In patients with chronic hepatitis C infection, health-related quality of life and work productivity are often impaired due to HCV-related fatigue. Treatment of hepatitis C with interferon-based regimens, which was the standard of care for all HCV patients until recently, had substantial and potentially debilitating side effects. These regimens caused additional impairment in health-related quality of life and work productivity during treatment and shortly after treatment cessation. The newly developed interferon-free combination of sofosbuvir and velpatasvir has been shown to improve health-related quality of life during treatment, and lead to an improvement in a number of indicators of patient-reported outcomes after successful clearance of HCV and achieving sustained virologic response.

Sofosbuvir plus Velpatasvir for Chronic Pangenotypic HCV Infection: Phase III Results

An experimental, once-daily pill for hepatitis C virus (HCV) leads to high rates of sustained virologic response across a wide range of patients, according to findings from four international, industry-supported, phase III trials reported below. The pill combines sofosbuvir (400 mg) with velpatasvir (100 mg; a novel pan-genotypic HCV NS5A inhibitor). The primary endpoint in all studies was sustained virologic response at 12 weeks after treatment ended (SVR12). Some 700 patients with HCV genotypes 1, 2, 4, and 6 were randomized to receive sofosbuvir–velpatasvir or placebo for 12 weeks; …