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All Studies   Meta Analysis    Recent:   

Inhaled remdesivir reduces viral burden in a nonhuman primate model of SARS-CoV-2 infection

Vermillion et al., Science Translational Medicine, doi:10.1126/scitranslmed.abl8282
Dec 2021  
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African green monkey study of inhaled versus IV remdesivir, showing similar efficacy with inhalation. Comparable concentrations of the active triphosphate in the lower respiratory tract were found with ~20x lower dose using inhalation, and there was lower systemic exposure to remdesivir and metabolites.
Gérard, Wu, Zhou show significantly increased risk of acute kidney injury with remdesivir.
5 preclinical studies support the efficacy of remdesivir for COVID-19:
Vermillion et al., 30 Dec 2021, peer-reviewed, 26 authors.
This PaperRemdesivirAll
Inhaled remdesivir reduces viral burden in a nonhuman primate model of SARS-CoV-2 infection
Meghan S Vermillion, Eisuke Murakami, Bin Ma, Jared Pitts, Adrian Tomkinson, Davin Rautiola, Darius Babusis, Hammad Irshad, Dustin Seigel, Cynthia Kim, Xiaofeng Zhao, Congrong Niu, Jesse Yang, Andrew Gigliotti, Nani Kadrichu, John P Bilello, Scott Ellis, Roy Bannister, Raju Subramanian, Bill Smith, Richard L Mackman, William A Lee, Philip J Kuehl, Jim Hartke, Tomas Cihlar, Danielle P Porter
Science Translational Medicine, doi:10.1126/scitranslmed.abl8282
Remdesivir (RDV) is a nucleotide analog prodrug with demonstrated clinical benefit in patients with coronavirus disease 2019 . In October 2020, the US FDA approved intravenous (IV) RDV as the first treatment for hospitalized COVID-19 patients. Furthermore, RDV has been approved or authorized for emergency use in more than 50 countries. To make RDV more convenient for non-hospitalized patients earlier in disease, alternative routes of administration are being evaluated. Here, we investigated the pharmacokinetics and efficacy of RDV administered by head dome inhalation in African green monkeys (AGM). Relative to an IV administration of RDV at 10 mg/kg, an approximately 20-fold lower dose administered by inhalation produced comparable concentrations of the pharmacologically active triphosphate in lower respiratory tract tissues. Distribution of the active triphosphate into the upper respiratory tract was also observed following inhaled RDV exposure. Inhalation RDV dosing resulted in lower systemic exposures to RDV and its metabolites as compared with IV RDV dosing. An efficacy study with repeated dosing of inhaled RDV in an AGM model of SARS-CoV-2 infection demonstrated reductions in viral replication in bronchoalveolar lavage fluid and respiratory tract tissues compared with placebo. Efficacy was observed with inhaled RDV administered once daily at a pulmonary deposited dose of 0.35 mg/kg beginning approximately 8 hours post-infection. Moreover, the efficacy of inhaled RDV was similar to that of IV RDV administered once at 10 mg/kg followed by 5 mg/kg daily in the same study. Together, these findings support further clinical development of inhalation RDV.
References
Alexander, Collins, Coombs, Gilkison, Hardy et al., Association of Inhalation Toxicologists (AIT) working party recommendation for standard delivered dose calculation and expression in non-clinical aerosol inhalation toxicology studies with pharmaceuticals, Inhal. Toxicol, doi:10.1080/08958370802207318
Assiri, Al-Tawfiq, Al-Rabeeah, Al-Rabiah, Al-Hajjar et al., Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study, Lancet Infect. Dis, doi:10.1016/S1473-3099(13)70204-4
Beigel, Tomashek, Dodd, Mehta, Zingman et al., ACTT-1 Study Group Members, Remdesivir for the Treatment of Covid-19 -Final Report, N. Engl. J. Med, doi:10.1056/NEJMoa2007764
Benech, Théodoro, Herbet, Page, Schlemmer et al., Peripheral blood mononuclear cell counting using a DNA-detectionbased method, Anal. Biochem, doi:10.1016/j.ab.2004.03.015
Blair, Vaccari, Doyle-Meyers, Roy, Russell-Lodrigue et al., Acute Respiratory Distress in Aged, SARS-CoV-2-Infected African Green Monkeys but Not Rhesus Macaques, Am. J. Pathol, doi:10.1016/j.ajpath.2020.10.016
Choi, Kang, Kim, Choi, Joh et al., Korean Society of Infectious Diseases, Clinical Presentation and Outcomes of Middle East Respiratory Syndrome in the Republic of Korea, Infect. Chemother, doi:10.3947/ic.2016.48.2.118
Hartman, Nambulli, Mcmillen, White, Tilston-Lunel et al., SARS-CoV-2 infection of African green monkeys results in mild respiratory disease discernible by PET/CT imaging and shedding of infectious virus from both respiratory and gastrointestinal tracts, PLOS Pathog, doi:10.1371/journal.ppat.1008903
Hill, Paredes Deiros, Vaca, Mera, Webb et al., Remdesivir for the treatment of high-risk non-hospitalized individuals with COVID-19: a randomized, double-blind, placebo-controlled trial
Humeniuk, Mathias, Cao, Osinusi, Shen et al., Safety, Tolerability, and Pharmacokinetics of Remdesivir, An Antiviral for Treatment of COVID-19, in Healthy Subjects, Clin. Transl. Sci, doi:10.1111/cts.12840
Ksiazek, Erdman, Goldsmith, Zaki, Peret et al., SARS Working Group, A novel coronavirus associated with severe acute respiratory syndrome, N. Engl. J. Med, doi:10.1056/NEJMoa030781
Li, Liclican, Xu, Pitts, Niu et al., Key Metabolic Enzymes Involved in Remdesivir Activation in Human Lung Cells, Antimicrob. Agents Chemother, doi:10.1128/AAC.00602-21
Mackman, Hui, Perron, Murakami, Palmiotti et al., Prodrugs of a 1′-CN-4-Aza-7,9-dideazaadenosine C-Nucleoside Leading to the Discovery of Remdesivir (GS-5734) as a Potent Inhibitor of Respiratory Syncytial Virus with Efficacy in the African Green Monkey Model of RSV, J. Med. Chem, doi:10.1021/acs.jmedchem.1c00071
Mers, Group, State of Knowledge and Data Gaps of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in Humans, PLOS Curr
Munster, Feldmann, Williamson, Van Doremalen, Pérez-Pérez et al., Respiratory disease in rhesus macaques inoculated with SARS-CoV-2, Nature, doi:10.1038/s41586-020-2324-7
Pitts, Lu, Du Pont, Riola, Li et al., Delta Variant and Other Variants of Concern
Speranza, Williamson, Feldmann, Sturdevant, Pérez-Pérez et al., Single-cell RNA sequencing reveals SARS-CoV-2 infection dynamics in lungs of African green monkeys, Sci. Transl. Med, doi:10.1126/scitranslmed.abe8146
Tepper, Kuehl, Cracknell, Nikula, Pei et al., Symposium Summary: "Breathe In, Breathe Out, Its Easy: What You Need to Know About Developing Inhaled Drugs, Int. J. Toxicol, doi:10.1177/1091581815624080
Warren, Jordan, Lo, Ray, Mackman et al., Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys, Nature, doi:10.1038/nature17180
Williamson, Feldmann, Schwarz, Meade-White, Porter et al., Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2, Nature, doi:10.1038/s41586-020-2423-5
Woolsey, Borisevich, Prasad, Agans, Deer et al., Establishment of an African green monkey model for COVID-19 and protection against re-infection, Nat. Immunol, doi:10.1038/s41590-020-00835-8
Wu, Mcgoogan, Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention, JAMA, doi:10.1001/jama.2020.2648
Wölfel, Corman, Guggemos, Seilmaier, Zange et al., Virological assessment of hospitalized patients with COVID-2019, Nature, doi:10.1038/s41586-020-2196-x
Zhu, Zhang, Wang, Li, Yang et al., China Novel Coronavirus Investigating and Research Team, A Novel Coronavirus from Patients with Pneumonia in China, N. Engl. J. Med, doi:10.1056/NEJMoa2001017
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