voxilaprevir (GS-9857) / Gilead - LARVOL DELTA

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

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

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

Challenges and synthetic opportunities of macrocyclization as a tool for the development of highly selective kinase inhibitors (ACS-Sp 2023) - "Recent drug approvals such as Lorlatinib, Pacritinib, Glecaprevir, or Voxilaprevir underline the clinical relevance of drug-like macrocycles. Thus, the orthosteric binding pocket of protein kinases is highly conserved and the development of macrocyclic kinase inhibitors is one strategy to overcome this problem. Here I will discuss the challenges and synthetic opportunities for the development of highly selective macrocyclic kinase inhibitors."

REAL-LIFE EFFECTIVENESS OF VOXILAPREVIR/VELPATASVIR/SOFOSBUVIR IN HEPATITIS C PATIENTS PREVIOUSLY TREATED WITH DIRECT-ACTING ANTIVIRAL AGENTS (DAA) (AASLD 2022) - "Patients received VOX/VEL/SOF for 12 weeks, ribavirin was added in 4% of treatment schedules...The most common prior DAA combinations were sofosbuvir plus an NS5A inhibitor (64%) or grazoprevir/elbasvir (12%)... Real-world data show that VOX/VEL/SOF is an effective rescue therapy for patients with prior DAA treatment failure despite the presence of resistance associated substitutions."

Clinical • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Inflammation • Liver Cirrhosis • Oncology • Solid Tumor

Infrequent hepatitis C genotypes/subtypes in patients treated with DAA-based regimens: successes and failures (EASL-ILC 2022) - "One cirrhotic genotype 1d patient failed 2 one-DAA-based regimens (telaprevir (TPV)/pegylated interferon (pegIFN)/Ribavirin (RBV); sofosbuvir (SOF)/pegIFN/RBV) was successfully retreated with SOF/ledipasvir (LDV). One cirrhotic genotype 1 k patient failed 4 DAA-based regimens (SOF/simeprevir (SIM); SOF/LDV 24/48 weeks; SOF/LDV/RBV). In a subgroup analysis of patients treated with a 2-last generation DAA (SOF/velpatasvir (VEL), SOF/VEL/RBV, glecaprevir (GLE)/pibrentasvir (PIB)), 50 patients were identified...A genotype 3b patient failed SOF/VEL for 12 weeks and was successfully retreated with SOF/VEL/ voxilaprevir (VOX) for 12 weeks... Our real-world data show that in patients with infrequent HCV genotypes/subtypes treated with 2 last-generation DAA the SVR rate is 90%. Although the data are limited, these results support the possibility of initially treating them with 2 lastgeneration DAA. More data are needed to determine optimal treatment regimen by genotype/subtype..."

Clinical • Fibrosis • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis • Transplantation

Effectiveness of pangenotypic retreatment of HCV infection after prior failure of pangenotypic therapies (EASL-ILC 2022) - "As shown in figure 1 primary glecaprevir/pribrentasivir (GP) based therapy was changed to velpatasvir/sofosbuvir (VS) based in 18, and VS to GP in 13 patients. In 6 patients, the same regimen was used, extending the duration of therapy or supplementing it with an additional drug (ribavirin (R), sofosbuvir (S), voxilaprevir (V))... We have demonstrated a high, almost 90% effectivenes of pangenotypic retreatment after failure of the primary pangenotypic therapy. Only men with cirrhosis, infected with genotype 3, did not eliminate HCV infection despite double pangenotypic treatment. We hope to provide data from more patients at the ILC."

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

Effectiveness of voxilaprevir/velpatasvir/sofosbuvir in hepatitis C patients previously treated with direct-acting antiviral agents (DAA) (EASL-ILC 2022) - "Patients received VOX/VEL/SOF for 12 weeks, ribavirin was added in 4% of treatment schedules. VOX/VEL/SOF is an effective retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. We identified HCV GT 3a and HCC as the main predictors of VOX/VEL/SOF failure."

Clinical • Fibrosis • Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Inflammation • Liver Cirrhosis • Oncology • Solid Tumor

In Vitro Assessment of Transporter Mediated Perpetrator DDIs for Several Hepatitis C Virus Direct-Acting Antiviral Drugs and Prediction of DDIs with Statins Using Static Models. (PubMed, AAPS J) - "Inhibitory effects of asunaprevir, daclatasvir, grazoprevir, paritaprevir, simeprevir, and voxilaprevir, direct-acting antiviral (DAA) drugs for the treatment of chronic hepatitis C virus (HCV) infection, were evaluated in vitro against a range of clinically important drug transporters...Furthermore, we refined and developed static models to predict complex DDIs with several statins (pitavastatin, rosuvastatin, atorvastatin, and pravastatin) by mechanistically assessing differential inhibitory effects of perpetrator drugs on multiple transporters, such as organic anion transporting polypeptides (OATP1B), breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), organic anion transporter 3 (OAT3), and cytochrome P450 CYP3A enzyme, as they are known to contribute to absorption, distribution, metabolism and excretion (ADME) of above statins...Our studies suggest that mechanistic static model is a promising and useful tool to provide more accurate..."

Journal • Preclinical • Breast Cancer • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Oncology • Solid Tumor

Deciphering the Molecular Mechanism of HCV Protease Inhibitor Fluorination as a General Approach to Avoid Drug Resistance. (PubMed, J Mol Biol) - "Third generation Hepatitis C virus (HCV) NS3/4A protease inhibitors (PIs), glecaprevir and voxilaprevir, are highly effective across genotypes and against many resistant variants...However, the molecular basis by which fluorination improves potency and resistance profile of HCV NS3/4A PIs is not well understood...Detailed analysis of the co-crystal structures revealed that PIs with fluorinated P4 caps can sample alternate binding conformations that enable adapting to structural changes induced by the D168A substitution. Our results elucidate molecular mechanisms of fluorine-specific inhibitor interactions that can be leveraged in avoiding drug resistance."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation

[VIRTUAL] MINIMAL DRUG-DRUG INTERACTIONS BETWEEN DIRECT- ACTING ANTIVIRALS AND HCC TREATMENTS – A TERRITORY- WIDE COHORT STUDY (AASLD 2021) - "Their mean age was 59±12 years, 1,807 (60.6%) were male; 810 (27.2%) had genotype 1 and 552 (18.5%) genotype 6 HCV; 771 (25.9%) received sofosbuvir/velpatasvir, 510 (17.1%) sofosbuvir/ledipasvir, and 865 (29.0%) glecaprevir/pibrentasvir...Sorafenib was used in two patients, and it has DDI with the 3D regimen and elbasvir/grazoprevir . Regorafenib is known to have DDI with various DDAs (3D contraindicated; DDI with sofosbuvir/ velpatasvir+/- voxilaprevir; weak DDI with elbasvir/grazoprevir and glecaprevir/pibrentasvir); yet regorafenib was not used in this cohort . . Five patients used immunotherapy namely pembrolizumab, nivolumab, atezolizumab and avelumab; so far no known DDI data are available of these immunotherapies with DAA (Table)... DDI between DAA and HCC treatment was rare . More data concerning DDI between immunotherapy and DAA would be helpful to guide the best DAA and HCC treatments for the patients . Table ."

Gastrointestinal Cancer • Hepatitis C • Hepatocellular Cancer • Oncology • Solid Tumor