presatovir (GS-5806) / Gilead - LARVOL DELTA

A New Paradigm for RSV Treatment: EV148 Leverages Pre-Existing Immunity to Achieve Strain-Independent Antiviral Efficacy in Neonatal Lambs (RSVVW 2026) - "Monoclonal antibodies such as palivizumab and nirsevimab provide prophylaxis for high-risk populations but demonstrate limited therapeutic efficacy in hospitalized patients with established infection...In therapeutic BALB/c mouse models, single-dose subcutaneous treatment 72 hours post-infection reduced nasal viral titers by >4.0 log₁₀ and viral RNA by >3.0 log₁₀—outperforming ribavirin, Presatovir, and investigational fusion inhibitors...Most critically, in blinded neonatal lamb studies—a translationally relevant large animal model that recapitulates human infant lower respiratory tract disease—single-dose EV148 administered 24 hours post-infection reduced gross lung lesions by 75%, significantly decreased viral titers in both lung tissue and bronchoalveolar lavage fluid with dose-dependent reductions in viral RNA, and prevented clinical disease progression including abnormal lung sounds and elevated resting respiratory rates. These data establish EV148 as a..."

Clinical • IO biomarker • Infectious Disease • Inflammation • Influenza • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNG • IL1B • IL6 • TNFA

A New Paradigm for RSV Treatment: EV148 Leverages Pre-Existing Immunity to Achieve Strain-Independent Antiviral Efficacy in Neonatal Lambs. (RSVVW 2026) - "Monoclonal antibodies such as palivizumab and nirsevimab provide prophylaxis for high-risk populations but demonstrate limited therapeutic efficacy in hospitalized patients with established infection...In therapeutic BALB/c mouse models, single-dose subcutaneous treatment 72 hours post-infection reduced nasal viral titers by >4.0 log₁₀ and viral RNA by >3.0 log₁₀—outperforming ribavirin, Presatovir, and investigational fusion inhibitors...Most critically, in blinded neonatal lamb studies—a translationally relevant large animal model that recapitulates human infant lower respiratory tract disease—single-dose EV148 administered 24 hours post-infection reduced gross lung lesions by 75%, significantly decreased viral titers in both lung tissue and bronchoalveolar lavage fluid with dose-dependent reductions in viral RNA, and prevented clinical disease progression including abnormal lung sounds and elevated resting respiratory rates. These data establish EV148 as a..."

Clinical • IO biomarker • Infectious Disease • Inflammation • Influenza • Pneumonia • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNG • IL1B • IL6 • TNFA

Systematic Review of the Efficacy and Safety of RSV-Specific Monoclonal Antibodies and Antivirals in Development. (PubMed, Rev Med Virol) - "Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633."

Journal • Review • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNA1

A randomized controlled trial of presatovir for respiratory syncytial virus after lung transplant. (PubMed, J Heart Lung Transplant) - P2b | "Presatovir treatment did not significantly improve change in nasal RSV load, symptoms, or lung function in lung transplant recipients."

Clinical • Journal • Infectious Disease • Influenza • Respiratory Diseases • Respiratory Syncytial Virus Infections • Transplantation

Evaluation of Small Molecule Combinations against Respiratory Syncytial Virus In Vitro. (PubMed, Molecules) - "Therefore, we tested in vitro two-drug combinations of fusion inhibitors (GS5806, Ziresovir and BMS433771) and RNA-dependent RNA polymerase complex (RdRp) inhibitors (ALS8176, RSV604, and Cyclopamine). On the other hand, all combinations between fusion inhibitors showed antagonistic effects against RSV in vitro, with volume of antagonism ranging from -50 µM % to -176 µM % at 95% confidence interval. Over all, our results suggest the potentially therapeutic combinations in combating RSV in vitro could be considered for further animal and clinical evaluations."

Journal • Preclinical • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Drug repurposing for identification of potential inhibitors against SARS-CoV-2 spike receptor-binding domain: An in silico approach. (PubMed, Indian J Med Res) - "Drugs such as chalcone, grazoprevir, enzaplatovir, dolutegravir, daclatasvir, tideglusib, presatovir, remdesivir and simeprevir were predicted to be potentially effective antiviral drugs against RBD and could have good COVID-19 therapeutic efficacy. In the current investigation, simeprevir was identified as the potential antiviral drug based on the in silico findings in comparison to remdesivir, favipiravir and other 53 drugs. Further, laboratory and clinical investigations are needed to be carried out which will aid in the development of quick therapeutics designed for COVID-19."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Neutrophils in respiratory syncytial virus infection: from harmful effects to therapeutic opportunities. (PubMed, Br J Pharmacol) - "Although antiviral drugs are obvious candidates to treat viral illness, and some have shown antiviral effects in humans, antivirals such as GS-5806, ALX-0171, ALS-8176 did not yet meet their expectations. It is unclear how these cells contribute to antiviral defense or whether they contribute to lung pathology. This article discusses the protective and harmful roles of neutrophils during RSV infection and provides an overview of mechanisms by which neutrophil function could be targeted to prevent tissue injury and preserve homeostasis."

Journal • Review • Immune Modulation • Immunology • Infectious Disease • Inflammation

Advances in respiratory virus therapeutics - A meeting report from the 6th isirv Antiviral Group conference. (PubMed, Antiviral Res) - "Updates were presented on several influenza antivirals including baloxavir, CC-42344, VIS410, immunoglobulin, immune plasma, MHAA4549A, pimodivir (JNJ-63623872), umifenovir, and HA minibinders; RSV antivirals including presatovir (GS-5806), ziresovir (AK0529), lumicitabine (ALS-008176), JNJ-53718678, JNJ-64417184, and EDP-938; broad spectrum antivirals such as favipiravir, VH244, remdesivir, and EIDD-1931/EIDD-2801; and host directed strategies including nitazoxanide, eritoran, and diltiazem. Other topics included considerations of novel endpoints such as ordinal scales and patient reported outcomes (PRO), and study design issues, and other regulatory considerations for antiviral drug development. The aim of this report is to provide a summary of the presentations given at this meeting."

Journal • Review • Infectious Disease • Novel Coronavirus Disease

RSVAdultLungTx: Presatovir in Lung Transplant (LT) Recipients With Respiratory Syncytial Virus (RSV) Infection (clinicaltrials.gov) - P2b; N=61; Completed; Sponsor: Gilead Sciences; Active, not recruiting ➔ Completed

Trial completion • Biosimilar

The Drug-Drug Interaction Profile of Presatovir. (PubMed, J Clin Pharmacol) - "This study enrolled 64 healthy subjects to evaluate the effect of cyclosporine, a P-gp, BCRP, and OATP1B1/1B3 inhibitor; rifampin, a strong CYP3A4 and P-gp inducer; efavirenz, a moderate CYP3A4 inducer; and cobicistat, a potent CYP3A inhibitor, on presatovir pharmacokinetics. These data support coadministration of presatovir with inhibitors of P-gp, BCRP, OATP1B1/1B3, or CYP3A, but not with moderate or strong CYP3A4 inducers. Presatovir was well-tolerated with the most common drug-related adverse events of dizziness (n = 12) and somnolence (n = 4) reported during efavirenz treatment."

Journal

Late therapeutic intervention with a respiratory syncytial virus L-protein polymerase inhibitor, PC786, on RSV infection in human airway epithelium. (PubMed, Br J Pharmacol) - "Late therapeutic intervention with the RSV polymerase inhibitor, PC786, reduced the viral burden quickly in human airway epithelium. Thus, PC786 demonstrates the potential to be an effective therapeutic agent to treat active RSV infection."

Biomarker • Journal