voxilaprevir (GS-9857) / Gilead - LARVOL DELTA

Improving immunotherapy response with direct-acting antiviral therapy in patients with advanced hepatocellular carcinoma and chronic hepatitis C virus infection. (ASCO 2026) - P4 | " In this open-label single-arm clinical trial (NCT05717400), patients with HCV-related HCC received atezolizumab plus bevacizumab and DAAs (sofosbuvir/velpatasvir [SV] or SV/voxilaprevir [SVV]). Early DAA therapy after ICT in patients with advanced HCC was safe and resulted in enhanced CD4⁺ and CD8⁺ T-cell responses with excellent virologic control but did not impact tumor response. Larger clinical trials are warranted to determine whether HCV clearance with DAA therapy enhances ICT response in patients with HCV-related HCC."

Clinical • IO biomarker • Metastases • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor • CD4 • CD68 • CD69 • CD8 • ICOS

Beyond the catalytic site: Voxilaprevir and Pasireotide as repurposed therapeutics for conformational inhibition of ADAR1. (PubMed, J Mol Graph Model) - "Given their established intersections with cancer biology, particularly Pasireotide's intrinsic antiproliferative activity, these findings champion a novel mechanism of ADAR1 inhibition via conformational trapping and steric occlusion. While experimental validation is required, these findings suggest an expanded and previously underexplored chemical space for ADAR1 modulation and support drug repositioning as a promising strategy for next-generation cancer immunotherapy."

Journal • Oncology • ADAR

Outcomes of Breakthrough Infections, Antiviral Resistance, and Cure Rates After Short Direct-Acting Antiviral (DAA) Prophylaxis in HCV-Viremic Kidney Donors to HCV-Negative Recipients (D+/R-) (ATC 2026) - "All subjects received an initial dose of sofosbuvir/velpatasvir (SOF/VEL) on day 0 ≤6 hours prior to transplant and then daily for a total of 7 days...Initial therapy consisted of glecaprevir/pibrentasvir (G/P) in 13 of 15 cases and SOF/VEL in 2 cases; one patient who failed G/P subsequently achieved SVR using SOF/VEL/voxilaprevir plus ribavirin for 12 weeks... Breakthrough HCV infection occurred in a small proportion (7.4%) of recipients receiving 7-day DAA prophylaxis after HCV D+/R- kidney transplantation. Although NS5A resistance-associated substitutions were identified in a subset of cases, the vast majority (93%) achieved sustained virologic response with a standard 12-week treatment course, and the single initial non-responder was cured with salvage therapy. These findings demonstrate that short prophylaxis yields low transmission rates, and that breakthrough infections—when they occur—remain consistently curable with appropriately selected DAA regimens."

Hepatitis C • Hepatology • Infectious Disease • Inflammation • Liver Failure

A Database-Derived Global Overview of HCV Resistance-Associated Substitutions: Characterizing Genotypic, Regional, and Temporal Heterogeneity. (PubMed, Int J Mol Sci) - "Importantly, RASs against pan-genotypic NS3 protease inhibitors (glecaprevir and voxilaprevir) were rare (generally <1% across genotypes)...The NS5B nucleotide analogue sofosbuvir retained a high genetic barrier, with the canonical S282T substitution detected only sporadically (2.1% of genotype 4 sequences)...Temporal analyses revealed an increase in NS3 and NS5A RASs following the introduction of first-generation DAAs, with NS5A substitutions persisting into the current interferon-free era, whereas NS5B resistance remained consistently rare across all treatment periods. Together, these findings provide a global, population-level overview of resistance-associated HCV diversity and reinforce the durability of high-barrier regimens while highlighting persistent genotype-specific vulnerabilities with implications for antiviral resistance surveillance and HCV elimination efforts."

Heterogeneity • Journal • Hepatitis C • Infectious Disease • Inflammation

Repurposing antiviral drugs targeting RNA viruses: A focus on the fusion protein of human metapneumovirus. (PubMed, North Clin Istanb) - "This study provides compelling in silico evidence that drug repurposing of clinically approved antiviral agents may accelerate the development of effective HMPV-specific therapies. By targeting the highly conserved and functionally critical HMPV F protein, the identified candidate compounds offer strong translational potential and justify prioritization for experimental validation and preclinical investigation. Collectively, these results contribute to filling a critical therapeutic gap and support drug repurposing as a viable and time-efficient strategy to address emerging and neglected viral respiratory infections."

Journal • Hepatitis C • Infectious Disease • Inflammation • Respiratory Diseases

Bloodborne infections in dental practice: prevalence of markers and phylogenetic analysis of circulating strains. (PubMed, Vopr Virusol) - "The study reveals high viral hepatitis prevalence among dental patients. Detection of drug-resistant HCV variants and immune-evading HBV strains underscores the need for enhanced molecular surveillance, improved diagnostic protocols, and strengthened infection control measures."

Journal • Hepatitis B • Hepatitis C • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Atomistic-Level Structural Insight into Vespa Venom (Ves a 1) and Lipid Membrane Through the View of Molecular Dynamics Simulation. (PubMed, Toxins (Basel)) - "The presence of voxilaprevir was observed to subtly alter these membrane interaction patterns and influence the enzyme's catalytic area, reflecting the inhibitor's impact within its physiological context. These results emphasize the crucial role of the lipid bilayer in shaping enzyme function and highlight voxilaprevir as a promising candidate for further inhibitor development, offering vital insights for rational drug design targeting membrane-associated proteins."

Journal

Impact of Resistance Associated Substitutions and Predictors of Treatment Failure Following Direct-acting Antiviral Therapy in a Viral Hepatitis C Elimination Cohort. (PubMed, J Clin Exp Hepatol) - P=N/A | "The National Viral Hepatitis Control Program (NVHCP) has a cure rate of 91.6% when using direct-acting antivirals (DAAs)-sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir) ± ribavirin in the Punjab hub-and-spoke model of hepatitis C virus (HCV) elimination...Among these Y93K, L30R, G30 H/R confer resistance to velpatasvir; such patients received retreatment with voxilaprevir-containing regimens...RAS do not appear to be a primary factor for treatment failure in a public health setting. NCT03488485 available from https://clinicaltrials.gov/study/NCT03488485."

Journal • Fibrosis • Hepatitis B • Hepatitis C • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation

Real-world outcomes in patients with Voxilaprevir (VOX)/Velpatasvir (VEL)/Sofosbuvir (SOF) treatment failure: a follow-up study (EASL 2025) - "Most of the patients had been pre-treated with VEL/SOF (55%, 17/31), 13% (4/31) each had received G/P (glecaprevir/pibrentasvir) or GZR/EBR(grazoprevir/elbasvir)±SOF and 10% (3/31) each had been pretreated with LDV(ledipasvir)/SOF or DCV(daclatasvir)/SOF. The combination of G/P+SOF represents an effective third-line treatment option for difficult-to-treat patients, including those with cirrhosis, HCC, or HCV GT3 infection. These findings highlight the importance of tailored salvage therapy to achieve optimal outcomes in this challenging population."

Clinical • Real-world • Real-world evidence • Fibrosis • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Oncology • Solid Tumor

Real-world outcomes in patients with Voxilaprevir (VOX)/Velpatasvir (VEL)/Sofosbuvir (SOF) treatment failure: a follow-up study (EASL 2025) - No abstract available

Clinical • Real-world • Real-world evidence • Hepatitis C • Hepatology • Infectious Disease

Retreatment of HCV in a large metropolis – implications for WHO elimination targets? The London experience (EASL 2025) - "SVR rates were higher in those treated with voxilaprevir-containing regimens (n=107, 73.8%) and differing non-voxilaprevir-containing regimens 1(n=167, 55.7%) The need for retreatment of HCV occurs more commonly in treatment failures rather than reinfection... The need for retreatment of HCV occurs more commonly in treatment failures rather than reinfection. The reinfection risk was higher in patients with HIV rather than current PWID. Retreatment with the same drug regimen was associated with worse outcomes."

Hepatitis C • Hepatology • Human Immunodeficiency Virus • Inflammation

Long-term efficacy and safety of sofosbuvir-based direct-acting antiviral regimens in paediatric patients with hepatitis C virus infection: an international registry study. (PubMed, Lancet Child Adolesc Health) - P=N/A | "No change in growth or sexual development was detected during prolonged follow-up of paediatric patients who had completed treatment with sofosbuvir-based direct-acting antivirals for chronic HCV. Prolonged clinical follow-up of children who have achieved sustained virological response might not be necessary."

Journal • Observational data • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Pediatrics

Exploring the potential of direct-acting antivirals against Chikungunya virus through structure-based drug repositioning and molecular dynamic simulations. (PubMed, Comput Biol Med) - "Our findings suggest repurposing hepatitis C virus (HCV) antivirals, specifically Simeprevir (SIM) and voxilaprevir (VOX), could be effective against CHIKV...To validate the results of our computational study, we evaluated the antiviral efficacy of SIM and VOX in vitro, both as monotherapies and in combination with ribavirin (RIBA)...Furthermore, the synergistic effects suggest that combining SIM and VOX with RIBA may provide a more effective therapeutic strategy than using either drug alone. Further research is necessary to optimize treatment protocols and improve outcomes for patients affected by CHIKV."

Journal • Chikungunya • Hepatitis C • Hepatology • Infectious Disease • Inflammation

HCV REINFECTION AMONG PEOPLE WHO USE DRUGS (PWUD) TREATED FOR HCV INFECTION: A LONG-TERM VIEW (AASLD 2024) - "All were maintained in care and offered re-treatment of HCV infection, with 1 getting glecaprevir/pibrentasvir (G/P) and 4 sofosbuvir/velpatasvir (S/V) according to their preference, and 6 still awaiting treatment...This patient is scheduled to receive S/V/voxilaprevir... To our knowledge, this is the largest single center longitudinal evaluation of HCV reinfection rates among active PWUD enriched for factors of instability (high rates of fentanyl use and unstable housing). We demonstrate that a comprehensive, multidisciplinary approach to HCV therapy with maintenance in follow up after cure is associated with rates of reinfection below 1/100 py. Those who experienced reinfection appear to disengage from ongoing follow up more frequently prior to the reinfection being documented."

CNS Disorders • Hepatitis C • Infectious Disease • Psychiatry

A case of vanishing hepatocellular carcinoma (AGW-GESA 2024) - "Following treatment with sofosbuvir, velpatasvir, and voxilaprevir after an initial failure with sofosbuvir and velpatasvir, she achieved sustained virologic response (SVR), and LFTs normalised. Spontaneous regression of HCC is rare. Meta-analysis of cases estimates incidence as 0.41%. Given scarcity of publications, it is difficult to ascertain causes of cure."

Clinical • Alzheimer's Disease • CNS Disorders • Fibrosis • Gastrointestinal Cancer • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Hypotension • Immunology • Infectious Disease • Liver Cancer • Mood Disorders • Oncology • Solid Tumor • Systemic Inflammatory Response Syndrome • AFP

Direct-Acting Antiviral Agents in Prevention of Maternal-Fetal Transmission of Hepatitis C Virus in Pregnancy. (PubMed, Pathogens) - "Prior to the Food and Drug Administration approval of ledipaspavir/sofosbuvir (Harvoni®) in 2014, the treatment of hepatitis C was interferon plus or minus ribavirin. The treatment of pregnant women with direct-acting antivirals is important because the treatment of pediatric patients cannot begin until three years of age and does not always occur prior to the symptom development of hepatitis C. This review article will include glecaprevir/pibrentasvir (Mayvret®), sofosbuvir/velpatasvir (Epclusa®), and sofosbuvir/velpatasvir plus voxilaprevir (Vosevi®). We aim to review the teratogenic risk of direct-acting antivirals as well as currently published clinical trials and ongoing research on direct-acting antiviral hepatitis C treatment in pregnancy in this publication."

Journal • Review • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Pediatrics

Sofosbuvir/Viplatasvir/Vosigrivir Retreatment of Hepatitis C Failed a NS5A-containing DAAs Regimen (APASL 2024) - "Case 1, male, 31 years old, with chronic hepatitis C, genotype 6a, took oral Sofosbuvir/Velpatasvir 1 tablet/d, once a day for 12 weeks...Sofosbuvir/velpatasivr/voxilaprevir is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs). The two cases we reported showed the use of Sofosbuvir/Viplatasvir/Vosigrivir combined with or without ribavirin therapy for patients who failed DAA treatment with NS5A inhibitors is effective and well tolerated. This group of cases represents an effective re-treatment program with good curative effects and few side effects."

Hepatitis C • Hepatology • Infectious Disease • Inflammation

Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure. (PubMed, JHEP Rep) - "The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%). The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF."

Journal • Real-world • Real-world effectiveness • Real-world evidence • Fibrosis • Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cancer • Oncology • Solid Tumor

REAL-WORLD EFFECTIVENESS OF VOXILAPREVIR/VELPATASVIR/SOFOSBUVIR IN DAA FAILURE PATIENTS: AN INTEGRATIVE ANALYSIS (AASLD 2023) - "The most common prior DAA combinations were ledipasvir/sofosbuvir (LDV/SOF), velpatasvir/sofosbuvir (VEL/SOF) and glecaprevir/pibrentasvir (G/P). VOX/VEL/SOF represents an effective retreatment for patients with HCV and prior DAA treatment failure. The addition of ribavirin or alternative retreatment with G/P+SOF, which was found to be effective in VOX/VEL/SOF treatment failures, may be considered in difficult-to-treat patients with HCV GT 3a, liver cirrhosis and liver cancer."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immunology • Liver Cancer • Liver Cirrhosis • Oncology • Solid Tumor

Recent Methods for the Synthesis of Quinoxaline Derivatives and their Biological Activities. (PubMed, Mini Rev Med Chem) - "Examples include glecaprevir (Mavyret), voxilaprevir (Vosevi), Balversa (L01EX16) (erdafitinib), carbadox, XK469R (NSC698215), and becampanel (AMP397). Recognizing the significance of these bioactive quinoxaline derivatives, researchers have dedicated their efforts to developing various synthetic methods for their production. This review aimed to compile the most recent findings on the synthesis and biological properties of quinoxaline derivatives from 2015 to 2023."

Journal • Human Immunodeficiency Virus • Infectious Disease • Oncology • Pain

Cost of Illness (COI) Associated with Direct Antiviral Agents (DAAs) for the Treatment of Hepatitis C Viral (HCV) Infection in India: A Systematic Literature Review (ISPOR-EU 2023) - "Mean drug cost/patient for 12 weeks with sofosbuvir+velpatasvir was INR43,447±21,247 in private and INR13,183±136 from state-government, with sofosbuvir+daclatasvir INR30,702±17,847 in private and INR4,019±849 from state-government, and with sofosbuvir+ledipasvir INR22,755±9,268 in private setting and INR9,576±0 from state-government...No study for voxilaprevir and its combination was identified... This SLR showed significant difference between market price (private) and state-government price for DAAs. High cost of DAAs is still a hinderance in HCV infection eradication. There was significant heterogeneity in costs among studies, so there is need to conduct more real-world studies on costs associated with HCV infection."

Review • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Pangenotypic triple versus double therapy in HCV-infected patients after prior failure of direct-acting antivirals. (PubMed, Clin Exp Hepatol) - "In the P2 group, two-thirds of patients were treated with velpatasvir/sofosbuvir, while in the P3 group the majority of patients received a combination of velpatasvir/sofosbuvir/voxilaprevir. A comparison of double and triple pangenotypic retherapy in patients after failure of DAA therapy showed a higher sustained virological response in the triple option with a comparable response at the end of therapy. The factors reducing the chances of cure were cirrhosis, genotype 3 infection and male gender."

Journal • Fibrosis • Hepatitis C • Hepatology • Immunology • Infectious Disease • Inflammation • Transplantation

Computational model for lipid binding regions in phospholipase (Ves a 1) from Vespa venom. (PubMed, Sci Rep) - "Furthermore, the MD simulation results indicated that voxilaprevir formed stable conformations within the catalytic pocket. Consequently, voxilaprevir could act as a potent inhibitor, opening up avenues for the development of more effective anti-venom therapeutics for Ves a 1."

Journal

Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in hepatitis C patients with prior failure to DAA treatment (EASL-ILC 2023) - "Ribavirin (RBV) was added in 8% of treatment courses and increased overall SVR rates (97%) as well as SVR rates in difficult-to-treat patients with HCV GT 3a (100%), liver cirrhosis (92.6%) and liver cancer (90%) insignificantly. Moreover, treatment effectiveness of rescue therapy with glecaprevir/pibrentasvir and sofosbuvir (G/P+SOF), which was initiated in 9 patients after VOX/VEL/SOF failure, was found to be high (SVR 12: 95%). VOX/VEL/SOF represents an effective standard therapy for patients with prior DAA treatment failure. The addition of RBV or alternative retreatment with G/P+SOF, which was found to be effective in VOX/VEL/SOF treatment failures, may be considered in difficult-to-treat patients with HCV GT 3a, liver cirrhosis and liver cancer."

Clinical • Real-world • Real-world effectiveness • Real-world evidence • Fibrosis • Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Liver Cancer • Liver Cirrhosis • Oncology • Solid Tumor

Real-life effectiveness of voxilaprevir/sofosbuvir/velpatasvir in hepatitis C patients previously treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir (EASL-ILC 2023) - "All patients received VOX/SOF/VEL ± ribavirin (RBV) for 12 weeks. VOX/SOF/VEL in the real world is an effective rescue therapy for failures to SOF/VEL or GLE/PIB. There is a trend towards higher SVR in patients previously treated with GLE/PIB. The addition of RBV to VOX/SOF/VEL could rise the rates of SVR and might be considered in patients with GT3, cirrhosis and prior failure to SOF/VEL."

Clinical • Fibrosis • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation