Effectiveness of baloxavir marboxil in nonhuman primates infected with highly pathogenic avian influenza A(H7N9) virus

Abstract: 

"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."

Iwatsuki-Horimoto, K., Imai, M., Ishibashi, T., Yamada, S., Kiso, M., Ito, M., Yasuhara, A., Yamayoshi, S. and Kawaoka, Y. (2026). Effectiveness of baloxavir marboxil in nonhuman primates infected with highly pathogenic avian influenza A(H7N9) virus. eBioMedicine, [online] 129, p.106350. doi:10.1016/j.ebiom.2026.106350.