Multi-center, Randomized, Double-blind, Placebo-controlled, Dose-ranging Study to Assess the Efficacy and Safety of the AV5080 Drug in Patients With Influenza

Assessment of the effect reached with the different doses of AV5080 on the duration and severity of influenza symptoms based on the incidence of their resolution within 96 hours from study treatment initiation compared to Placebo.
The absence of influenza symptoms or their reduction to mild severity for at least 24 hours indicates the resolution of influenza.

Start Date13 Nov 2017

Sponsor / Collaborator

Viriom, Inc.

100 Clinical Results associated with AV5080

100 Translational Medicine associated with AV5080

100 Patents (Medical) associated with AV5080

Literatures (Medical) associated with AV5080

01 Sep 2023·Antiviral Research

Resistance profiles for the investigational neuraminidase inhibitor AV5080 in influenza A and B viruses

Article

Author: Karapetian, Ruben N ; Shkil, Dmitry O ; Ivashchenko, Andrei A ; Govorkova, Elena A ; Penaflor, Melissa K ; Jones, Jeremy C ; Ivachtchenko, Alexandre V ; Ivanenkov, Yan A ; Pascua, Philippe Noriel Q

Neuraminidase inhibitors (NAIs) are recommended for influenza treatment and prevention worldwide. The most widely prescribed NAI is oral oseltamivir, while inhaled zanamivir is less commonly used. Using phenotypic neuraminidase (NA) enzymatic assays and molecular modeling approaches, we examined the ability of the investigational orally-dosed NAI AV5080 to inhibit viruses of the influenza A(H1N1)pdm09, A(H3N2), A(H5N1), and A(H7N9) subtypes and the influenza B/Victoria- and B/Yamagata-lineages containing NA substitutions conferring oseltamivir or zanamivir resistance including: NA-R292K, NA-E119G/V, NA-H274Y, NA-I122L/N, and NA-R150K. Broadly, AV5080 showed enhanced in vitro efficacy when compared with oseltamivir and/or zanamivir. Reduced AV5080 inhibition was determined for influenza A viruses with NA-E119G and NA-R292K, and for B/Victoria-lineage viruses with NA-I122N/L and B/Yamagata-lineage virus with NA-R150K. Molecular modeling suggested loss of the short hydrogen bond to the carboxyl group of AV5080 affected inhibition of NA-R292K viruses, whereas loss of the salt bridge with the guanidine group of AV5080 affected inhibition of NA-E119G. The resistance profiles and predicted binding modes of AV5080 and zanamivir are most similar, but dissimilar to those of oseltamivir, in part because of a guanidine moiety compensatory binding effect. Overall, our data suggests that AV5080 is a promising orally-dosed NAI that exhibited similar or superior in vitro efficacy against viruses with reduced or highly reduced inhibition phenotypes with respect to currently approved NAIs.

01 Sep 2023·Antiviral Research

Antiviral susceptibility of clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses isolated from birds and mammals in the United States, 2022

Article

Author: Jang, Yunho ; Jones, Joyce ; Wentworth, David E ; De La Cruz, Juan ; Torchetti, Mia K ; Di, Han ; Ivashchenko, Andrei A ; Chesnokov, Anton ; Nguyen, Ha T ; Davis, Charles T ; Killian, Mary Lea ; Mishin, Vasiliy P ; Pascua, Philippe Noriel Q ; Lantz, Kristina ; Gubareva, Larisa V ; Ivachtchenko, Alexandre V

Clade 2.3.4.4b highly pathogenic avian influenza (HPAI) A(H5N1) viruses that are responsible for devastating outbreaks in birds and mammals pose a potential threat to public health. Here, we evaluated their susceptibility to influenza antivirals. Of 1,015 sequences of HPAI A(H5N1) viruses collected in the United States during 2022, eight viruses (∼0.8%) had a molecular marker of drug resistance to an FDA-approved antiviral: three adamantane-resistant (M2-V27A), four oseltamivir-resistant (NA-H275Y), and one baloxavir-resistant (PA-I38T). Additionally, 31 viruses contained mutations that may reduce susceptibility to inhibitors of neuraminidase (NA) (n = 20) or cap-dependent endonuclease (CEN) (n = 11). A panel of 22 representative viruses was tested phenotypically. Overall, clade 2.3.4.4b A(H5N1) viruses lacking recognized resistance mutations were susceptible to FDA-approved antivirals. Oseltamivir was least potent at inhibiting NA activity, while the investigational NA inhibitor AV5080 was most potent, including against NA mutants. A novel NA substitution T438N conferred 12-fold reduced inhibition by zanamivir, and in combination with the known marker N295S, synergistically affected susceptibility to all five NA inhibitors. In cell culture-based assays HINT and IRINA, the PA-I38T virus displayed 75- to 108-fold and 37- to 78-fold reduced susceptibility to CEN inhibitors, baloxavir and the investigational AV5116, respectively. Viruses with PA-I38M or PA-A37T showed 5- to 10-fold reduced susceptibilities. As HPAI A(H5N1) viruses continue to circulate and evolve, close monitoring of drug susceptibility is needed for risk assessment and to inform decisions regarding antiviral stockpiling.

01 Jul 2014·Journal of Antimicrobial ChemotherapyQ2 · MEDICINE

Novel oral anti-influenza drug candidate AV5080

Q2 · MEDICINE

Article

Author: Ivachtchenko, Alexandre V ; Yamanushkin, Pavel M ; Veselov, Mark S ; Borisova, Olga V ; Ivanenkov, Yan A ; Bichko, Vadim V ; Mitkin, Oleg D ; Leneva, Irina A ; Karapetian, Ruben N ; Shevkun, Natalia A

OBJECTIVESDevelopment of a novel drug candidate with improved potency against influenza virus neuraminidase compared with currently available therapeutics, and high activity against oseltamivir-resistant viruses.METHODSA number of synthetic compounds were evaluated for antiviral properties in vitro and in vivo. Three-dimensional molecular docking, assisted by a pharmacophore model, was applied to classify compounds within the series by their inhibitory potency. Compound stability in blood and in animal models was determined. Pharmacokinetic studies in dogs and rats after oral or intravenous administration were performed.RESULTSA novel highly potent drug candidate [(3R,4R,5S)-5-[(diaminomethylene)amino]-3-(1-ethylpropoxy)-4-[(fluoroacetyl)amino]cyclohex-1-ene-1-carboxylic acid; AV5080] was synthesized and tested. AV5080 exhibited high activity against influenza virus neuraminidase in vitro, with IC(50) values of 0.03 nM and 0.07 nM against the neuraminidase of A/Duck/Minnesota/1525/1981/H5N1 and A/Perth/265/2009/H1N1 (wild-type), respectively. Notably, AV5080 was highly active against oseltamivir-resistant influenza viruses.CONCLUSIONSBased on the results presented in this study, AV5080 is a promising novel oral drug candidate for the treatment of influenza, including oseltamivir-resistant types. Further pre-clinical development of AV5080 is warranted.

100 Deals associated with AV5080

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Indication	Highest Phase	Country/Location	Organization	Date
Influenza, Human	Phase 3	RU	Viriom, Inc.	15 Jan 2022

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