velpatasvir (GS-5816) / Gilead - LARVOL DELTA

In silico screening of potential FGF2 inhibitors for cancer therapy. (PubMed, In Silico Pharmacol) - "Molecular docking study showed Elbasvir (1) to exhibit the strongest binding affinity (-8.1 kcal/mol), followed by Velpatasvir (2) (-7.6 kcal/mol), Daclatasvir (3) (-7.5 kcal/mol), Ritonavir (4) (-6.2 kcal/mol), Paliperidone Palmitate (5) (-5.9 kcal/mol), Saralasin (6) (-5.4 kcal/mol), Nystatin (8) (-5.2 kcal/mol), and Cobicistat (-5.1 kcal/mol)...Overall, the study provides mechanistic insights into the molecular interactions between FGF2 and these candidate drugs, highlighting the promising potential of compounds 1-6 and 8 for subsequent in vitro validation in cancer therapeutics. The online version contains supplementary material available at 10.1007/s40203-025-00495-2."

Journal • Acute Myelogenous Leukemia • Brain Cancer • Breast Cancer • Gastric Cancer • Glioblastoma • Hematological Malignancies • Leukemia • Lung Cancer • Nasopharyngeal Carcinoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • FGF2 • FGFR

Long-term changes in hepatic reserve and prognosis after direct-acting antiviral treatment in patients with hepatitis C virus-related decompensated cirrhosis: a five-year follow-up study of a Japanese phase 3 trial. (PubMed, J Gastroenterol) - "In HCV-related decompensated cirrhosis, 5 year LT-free survival rate after DAA was 74.7%, and viral clearance and post-treatment Child-Pugh class were associated with long-term prognosis. Child-Pugh class improved until 24 weeks after EOT, but little change was observed thereafter, which was closely associated with albumin levels."

Journal • P3 data • Fibrosis • Hepatitis C • Immunology • Infectious Disease • Inflammation • Transplantation

LIVERRISK SCORE EFFECTIVELY PREDICTS FIBROSIS PROGRESSION AND MORTALITY IN HCV PATIENTS TREATED WITH DIRECT-ACTING ANTIVIRALS (UEGW 2025) - "A total of 26(38.2%) patients underwent upper endoscopy, among whom 13(19.11%) had esophageal varices, 2(2.9%) had gastric or gastroesophageal varices (GOV), and 9(13.2%) presented with hypertensive gastropathy.46(75.4%) were treated with Sofosbuvir and Daclatasvir, followed by Sofosvubir and Velpatasvir for 9(14.8%). The LiverRisk score is an accurate tool to predict liver fibrosis and mortality in HCV patients treated with direct acting antivirals."

Clinical • Addiction (Opioid and Alcohol) • Cardiovascular • Cholestasis • Diabetes • Fibrosis • Gastroenterology • Hematological Disorders • Hepatitis B • Hepatitis C • Hepatology • Hypertension • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Portal Hypertension • Thrombocytopenia

OUTCOMES OF DIRECT ACTING ANTIVIRAL AGENTS IN CHRONIC HEPATITIS C PATIENTS WITH PRE-EXISTING HEPATOCELLULAR CARCINOMA (AASLD 2025) - "Patients were administered various DAAs; daclatasvir+asunaprevir, sofosvubir+ribavirin, sofosbuvir+daclatasvir, ledipasvir/Sofosbuvir±ribavirin, ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin, glecaprevir/pibrentasvir, velpatasvir/Sofobuvir ± ribavirin. This study demonstrated that the DAAs achieved favorable treatment outcomes and was well tolerated in CHC patients with pre-existing HCC. HCC tumor stage, presence of viable HCC and ribavirin use was significantly associated with survival."

Clinical • Hepatitis C • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor

Assessment of direct-acting antiviral treatment outcomes in patients with chronic hepatitis C infected with various HCV genotypes: Insights from a real-world cohort in West Bengal, India. (PubMed, BMC Infect Dis) - "This study highlights genotype-specific variations in treatment response, with GT-3b exhibiting lower treatment response which highlights the need to decipher the reasons behind treatment failure for future therapeutic management."

Journal • Real-world evidence • Retrospective data • Hepatitis C • Hepatology • Infectious Disease • Inflammation • Novel Coronavirus Disease

Hepatitis C Virus Cascade of Care After the Introduction of Direct-Acting Antiviral Medications in Suriname. (PubMed, Cureus) - "Although treatment with DAAs in Suriname is highly efficacious, several hurdles, including improving linkage and access to treatment, must be addressed to reduce the disease burden of HCV in Suriname successfully."

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

Key population-led test and treat for hepatitis C virus infection in Thailand enables rapid initiation of treatment and achieved high virological success rates (IAS-HIV 2025) - "Those who met simplified treatment criteria (absence of advanced fibrosis score, hepatitis B (HBV) co-infection, or other medical concerns) received 12-week oral direct-acting antivirals (DAAs – sofosbuvir 400mg and velpatasvir 100mg once daily). KP-led HCV test-and-treat intervention enabled quick confirmation of active HCV-infection, quick DAAs initiation, and high rates of treatment completion and SVR. Clients referred out for treatment often did not initiate DAAs or did so after significant delays. To increase rates of SVR assessment, barriers for SVR testing should be explored to design and implement targeted interventions."

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

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

The Genotypes/Subtypes and Antiviral Drug Resistance of the Hepatitis C Virus from Patients in a Tertiary Care Hospital in Nepal. (PubMed, Viruses) - "Resistant mutations against sofosbuvir, pibrentasvir, velpatasvir, daclatasvir, and dasabuvir were found at 25%, 18%, 16%, 16%, and 2%, respectively, mostly on subtype 3a. The predominant HCV genotype/subtype in our patient group was 3a, and resistance mutations against direct-acting antivirals were found in most untreated patients."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation

High rates of active hepatitis C (HCV) infection and rapid treatment initiation: results from Thailand's first key population-led HCV test and treat intervention (APASL 2025) - "Those with active HCV infection received telehealth consultations with physicians from affiliated sites, and clients eligible for simplified treatment (absence of cirrhosis, hepatitis B co-infection, or other medical concerns) received 12 weeks of once-daily fixed dose combination of sofosbuvir (400mg) and velpatasvir (100mg). We observed high HCV infection rates among men who have sex with men and transgender women, as well as high rates of co-infections with HIV and other STIs. Onsite HCV-RNA testing facilitated the rapid identification of active HCV infection and all clients eligible for simplified treatment initiated direct acting antivirals within a week. Clients referred out for treatment were less likely to initiate treatment, or did so with significant delays."

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

Prevalence of resistance-associated substitutions (RAS) in hepatitis C virus in the Former Soviet Union countries. (PubMed, BMJ Open Gastroenterol) - "The high prevalence of HCV genotypes 1b and 3a in the FSU region and the presence of specific RASs should be considered when determining the most effective treatment regimen for HCV-infected individuals in the FSU countries."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation

Retreatment of patients with chronic hepatitis C, subtype 3a, and cirrhosis, who previously failed a regimen containing second-generation NS5A inhibitors with sofosbuvir + glecaprevir/pibrentasvir and ribavirin for 16-24 weeks. (PubMed, J Virol) - "The outcomes of retreatment patients infected with hepatitis C virus genotype 3, cirrhosis, with velpatasvir may be affected by treatment failure with velpatasvir. The presence of NS5A resistance-associated substitution mutations, including Y93H, and the number and regimens of the past failed therapy do not influence the likelihood of achieving sustained virological response. When velpatasvir treatment fails, pibrentasvir should be used as the first choice for retreatment."

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

Reinfection and resistance associated substitutions following a minimal monitoring approach for HCV treatment in MINMON trial. (PubMed, Clin Infect Dis) - "Accounting for reinfections, SVR in MINMON was 97.0% further supporting simplified HCV treatment. No significant difference in SVR was found by baseline velpatasvir RAS. The high reinfection rate, especially among MSM with HIV, underscores the need to scale-up evidence-based interventions to reduce reinfection."

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

Real-World Experience, Effectiveness, and Safety of Direct-Acting Antivirals for the Treatment of Hepatitis C in Oman: A Cross-Sectional, Multicenter Study. (PubMed, J Clin Med) - " A cross-sectional study was conducted including 375 HCV patients with different genotypes, treated using different DAA regimens, with or without ribavirin, between January 2012 and December 2020 at the Sultan Qaboos University Hospital and the medical city for military and security services, two tertiary hospitals in Muscat, Oman...No significant adverse effects were reported. Based on our real-world experience, DAAs are highly effective in treating patients with HCV infection in Oman, with an excellent tolerability and safety profile."

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

Predictors of hepatitis C treatment failure in people living with HIV (HIV-Glasgow 2024) - "They received treatment with DAA, specifically Sofosfuvir with Velpatasvir by availability in our care center, the viral HCV RNA was measured at 12 weeks after finishing treatment to determine whether sustained virological response existed or not. Patients living with HIV infection who have experienced previous treatment failures are likely to show lower adherence to hepatitis C virus infection treatment. Also patients with psychiatric disorders are in risk of lower adherence to treatment of hepatitis C. This information would support us to pay more attention to these population groups to avoid treatment failures and reduce the potential transmission risk of resistant strains of hepatitis C."

CNS Disorders • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Mental Retardation • Psychiatry

PREDICTORS OF TREATMENT FAILURE AND RESISTANCE ASSOCIATED SUBSTITUTIONS IN PATIENTS WITH CHRONIC HEPATITIS C INFECTIONS - HCV ELIMINATION EXPERIENCE FROM THE PUNJAB MODEL IN INDIA (AASLD 2024) - P=N/A | "We collected the clinical and virological data for the ~8% treatment failure cases to ascertain presence of resistance associated substitutions (RAS) and clinical predictors of treatment failure when using generic direct-acting antivirals (DAAs)- sofosbuvir with an NS5A inhibitor (ledipasvir, daclatasvir or velpatasvir) ± ribavirin in a public health setting. RAS is not the primary factor for treatment failure in a public health setting in Punjab, India. Factors such as prior treatment experience, poor adherence to treatment, drug compliance and poor liver function predicted treatment failures."

Clinical • Cardiovascular • Diabetes • Fibrosis • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Hypertension • Immunology • Infectious Disease • Inflammation • Metabolic Disorders

TRENDS IN HCV SCREENING, FOLLOW-UP TESTING, AND TREATMENT IN PREGNANT PEOPLE AND INFANTS IN A TERTIARY CARE CENTER (AASLD 2024) - "Of the 32 with viremia, none received antiviral therapy during pregnancy; 9 (28.1%) received postpartum antiviral therapy (3 with ledipasvir-sofosbuvir, 1 with daclatasvir-sofosbuvir, 1 with elbasvir-grazoprevir, 1 with velpatasvir-sofosbuvir, 3 with unknown regimens). From 2014-2023, HCV screening in pregnancy improved to 66%, but remained much lower than universal screening recommendations. HCV viremia was < 1%, with no identified perinatal transmission. However, 58% of babies and 72% of mothers were lost to follow-up, supporting the need for improved screening as well as referral during pregnancy, postpartum, and for pediatric care."

Hepatitis C • Hepatology • Infectious Disease • Inflammation • Pediatrics • Small for Gestational Age

Drug repositioning identifies potential autophagy inhibitors for the LIR motif p62/SQSTM1 protein. (PubMed, Comput Biol Chem) - "The results revealed that the kanamycin, velpatasvir, verteporfin, and temoporfin significantly decreased the binding of LIR to the p62 protein. Finally, we experimentally confirmed that Kanamycin can inhibit autophagy-associated acidic vesicular formation in breast cancer MCF-7 and MDA-MB 231 cells. These repositioned drugs may represent novel autophagy modulators in clinical management, warranting further investigation."

Journal • Breast Cancer • Oncology • Solid Tumor • SQSTM1

An environmentally sustainable synchronous spectrofluorimetric method coupled with second derivative signal processing for simultaneous determination of velpatasvir and simeprevir in pharmaceutical and plasma samples. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Velpatasvir and simeprevir are two direct acting antivirals that are often used in combination with sofosbuvir to treat HCV infections. The method was very sensitive, with lower detection limits of 1.11 ng/mL and 25.40 ng/mL, and quantification limits of 3.36 ng/mL and 76.96 ng/mL for velpatasvir and simeprevir, respectively.The method was effectively used to determine velpatasvir and simeprevir simultaneously in their pure forms, pharmaceutical dosage forms, and human plasma with no interference. The suggested technique was additionally evaluated for its eco-friendliness through the utilization of the Analytical GREEnness (AGREE) and Green Analytical Procedure Index (GAPI) evaluation metrics, revealing that the method is indeed sustainable."

Journal • Hepatitis C • Infectious Disease

Analysis of the susceptibility of refractory hepatitis C virus resistant to nonstructural 5A inhibitors. (PubMed, Sci Rep) - "Compared with the WT, the Q24K/L28M/R30Q/A92K RASs was 36,000-fold resistant to daclatasvir, 440,000-fold resistant to ledipasvir, 6300-fold resistant to velpatasvir, 3100-fold resistant to elbasvir, and 1.8-fold resistant to pibrentasvir. Furthermore, a combination of pibrentasvir and sofosbuvir showed therapeutic efficacy against these RASs. Combination regimens may eradicate HCV with NS5A Q24K/L28M/R30E/A92K RASs."

Journal • Hepatitis C • Hepatology • Infectious Disease • Inflammation

INHIBITORS OF THE NON-STRUCTURAL PROTEIN 5A: FROM THE CONTROL OF HEPATITIS C TO THAT OF MALARIA? (EHA 2024) - "We have shownthat TD-6450, an NS5A inhibitor of hepatitis C virus (iNS5AHCV) kills the asexual stages, responsible forsymptoms and stiffens mature gametocytes of Plasmodium falciparum, responsible for transmission...The 3 NS5Ai (velpatasvir, elbasir, ravidasvir) are as effective on either P. falciparum artemisinin-sensitive (F-32TEM) and artemisinin-resistant (F32-ART) strains with IC50s lower than 2µM... All iNS5AHCV tested are active against P. falciparum (class effect). Ravidasvir, recently approved for thetreatment of hepatitis C in Indonesia (at a very low cost), is effective against the different stages of P. falciparum. If this multi-stage antimalarial activity is clinically confirmed, the addition of ravidasvir to combinedantimalarial treatments would generate multi-therapies that are resilient to resistance and effective intransmission blocking."

Hepatitis C • Hepatology • Infectious Disease • Inflammation • Malaria

Bioequivalence Study of Velpatasvir/Sofosbuvir Oral Coated Tablets in Healthy Volunteers Under Fasting Conditions. (PubMed, Clin Pharmacol Drug Dev) - "Criteria for bioequivalence were met for both area under the concentration-time curve from time 0 until the last quantifiable sample and peak concentration parameters. No adverse effects were reported during this trial in both groups."

Journal • Hepatology • Infectious Disease • Inflammation

Discovery of Bacterial Key Genes from 16S rRNA-Seq Profiles That Are Associated with the Complications of SARS-CoV-2 Infections and Provide Therapeutic Indications. (PubMed, Pharmaceuticals (Basel)) - "Then, we detected bKG-guided top-ranked eight drug molecules (Bemcentinib, Ledipasvir, Velpatasvir, Tirilazad, Acetyldigitoxin, Entreatinib, Digitoxin, and Elbasvir) by molecular docking. Finally, the binding stability of the top-ranked three drug molecules (Bemcentinib, Ledipasvir, and Velpatasvir) against three receptors (hldD, mlaA, and lptD) was investigated by computing their binding free energies with molecular dynamic (MD) simulation-based MM-PBSA techniques, respectively, and was found to be stable. Therefore, the findings of this study could be useful resources for developing a proper treatment plan against bacterial co-/super-/secondary-infection in SARS-CoV-2 infections."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases