tetano
Editor, Senior Moderator
EBioMedicine
. 2026 Jun 25:129:106350.
doi: 10.1016/j.ebiom.2026.106350. Online ahead of print.
Effectiveness of baloxavir marboxil in nonhuman primates infected with highly pathogenic avian influenza A(H7N9) virus
Kiyoko Iwatsuki-Horimoto[SUP] 1 [/SUP], Masaki Imai[SUP] 2 [/SUP], Toru Ishibashi[SUP] 3 [/SUP], Shinya Yamada[SUP] 4 [/SUP], Maki Kiso[SUP] 5 [/SUP], Mutsumi Ito[SUP] 4 [/SUP], Atsuhiro Yasuhara[SUP] 4 [/SUP], Seiya Yamayoshi[SUP] 6 [/SUP], Yoshihiro Kawaoka[SUP] 7 [/SUP]
Affiliations
Background: Highly pathogenic avian influenza (HPAI) A(H7N9) virus poses a potential public health threat, underscoring the need for effective antiviral options for outbreak preparedness. Baloxavir marboxil (BXM) is a cap-dependent endonuclease inhibitor approved for seasonal influenza, but its in vivo efficacy against HPAI A(H7N9) virus has not been fully evaluated.
Methods: We evaluated the efficacy of BXM in cynomolgus macaques infected with a reverse genetics-generated HPAI A(H7N9) virus. Animals received either low- or high-dose BXM, single-dose oseltamivir, or vehicle at 4 or 48 h post-infection (hpi). BXM administration was designed to mimic human pharmacokinetics. Viral titres, body temperature, body weight, lung pathology, and treatment-emergent viral substitutions were analysed.
Findings: Early treatment (4 hpi) with BXM significantly reduced viral titres in nasal and tracheal swabs, lessened weight loss, and decreased pulmonary inflammation and alveolar damage compared to untreated or oseltamivir-treated animals. Virus pathogenicity was relatively mild; no animals died. Delayed treatment (48 hpi) showed limited benefit. The PA-I38T (83.8%) and PA-E23G (78.6%) substitutions associated with BXM resistance were detected in one animal, and a PA-K34R (85.4%) substitution was detected in another animal. These substitutions reduce BXM susceptibility and were detected at low titres.
Interpretation: Although the dosing regimen used in this study involved repeat dosing to achieve the plasma drug concentrations after a single dose in humans, these findings highlight the importance of early antiviral intervention and support BXM use as a potential countermeasure against HPAI A(H7N9) virus infection, as resistance-associated substitutions remained limited in the macaque model. BXM may be a valuable therapeutic option for HPAI A(H7N9) virus infections.
Funding: Supported by the Japan Agency for Medical Research and Development (JP20wm0125002, JP223fa627001) and Shionogi & Co., Ltd.
Keywords: A(H7N9); Baloxavir marboxil; HPAI; Influenza virus; Nonhuman primate.
. 2026 Jun 25:129:106350.
doi: 10.1016/j.ebiom.2026.106350. Online ahead of print.
Effectiveness of baloxavir marboxil in nonhuman primates infected with highly pathogenic avian influenza A(H7N9) virus
Kiyoko Iwatsuki-Horimoto[SUP] 1 [/SUP], Masaki Imai[SUP] 2 [/SUP], Toru Ishibashi[SUP] 3 [/SUP], Shinya Yamada[SUP] 4 [/SUP], Maki Kiso[SUP] 5 [/SUP], Mutsumi Ito[SUP] 4 [/SUP], Atsuhiro Yasuhara[SUP] 4 [/SUP], Seiya Yamayoshi[SUP] 6 [/SUP], Yoshihiro Kawaoka[SUP] 7 [/SUP]
Affiliations
- PMID: 42349254
- DOI: 10.1016/j.ebiom.2026.106350
Background: Highly pathogenic avian influenza (HPAI) A(H7N9) virus poses a potential public health threat, underscoring the need for effective antiviral options for outbreak preparedness. Baloxavir marboxil (BXM) is a cap-dependent endonuclease inhibitor approved for seasonal influenza, but its in vivo efficacy against HPAI A(H7N9) virus has not been fully evaluated.
Methods: We evaluated the efficacy of BXM in cynomolgus macaques infected with a reverse genetics-generated HPAI A(H7N9) virus. Animals received either low- or high-dose BXM, single-dose oseltamivir, or vehicle at 4 or 48 h post-infection (hpi). BXM administration was designed to mimic human pharmacokinetics. Viral titres, body temperature, body weight, lung pathology, and treatment-emergent viral substitutions were analysed.
Findings: Early treatment (4 hpi) with BXM significantly reduced viral titres in nasal and tracheal swabs, lessened weight loss, and decreased pulmonary inflammation and alveolar damage compared to untreated or oseltamivir-treated animals. Virus pathogenicity was relatively mild; no animals died. Delayed treatment (48 hpi) showed limited benefit. The PA-I38T (83.8%) and PA-E23G (78.6%) substitutions associated with BXM resistance were detected in one animal, and a PA-K34R (85.4%) substitution was detected in another animal. These substitutions reduce BXM susceptibility and were detected at low titres.
Interpretation: Although the dosing regimen used in this study involved repeat dosing to achieve the plasma drug concentrations after a single dose in humans, these findings highlight the importance of early antiviral intervention and support BXM use as a potential countermeasure against HPAI A(H7N9) virus infection, as resistance-associated substitutions remained limited in the macaque model. BXM may be a valuable therapeutic option for HPAI A(H7N9) virus infections.
Funding: Supported by the Japan Agency for Medical Research and Development (JP20wm0125002, JP223fa627001) and Shionogi & Co., Ltd.
Keywords: A(H7N9); Baloxavir marboxil; HPAI; Influenza virus; Nonhuman primate.