Baloxavir marboxil is an oral prodrug that is rapidly converted to its active form baloxavir acid, a potent inhibitor of influenza cap-dependent endonuclease function of influenza A and B viruses. Baloxavir was approved for treatment of uncomplicated influenza A and B virus infections in 2018 in Japan (for those weighing >10 kg) and the United States (for those aged 12 years and older)
Key nonclinical characteristics of baloxavir include broad spectrum activity against various types and subtypes of influenza virus strains in vitro as well as rapid and profound reduction in viral load in vivo. The phase III study (CAPSTONE-1) was a multicenter, randomised, double-blind, placebo- and oseltamivir-controlled study of otherwise-healthy patients in Japan and US (n=1436). The primary endpoint was time to alleviation of influenza symptoms (TTAS). TTAS was shorter with baloxavir than placebo (median 53.7 hr vs 80.2 hr, p<0.0001). Median time to cessation of viral shedding was 24 hr in baloxavir-treated patients, compared with 72 hr for oseltamivir (p<0.0001) and 96 hr for placebo (p<0.0001). Baloxavir was well tolerated and appeared to have no significant safety issues identified. Testing of laboratory isolates passage or clinical isolates identified isoleucine-to-threonine substitution at amino acid position 38 in N-terminal domain (PA/I38T). PA/I38 substitutions conferred reduced susceptibility to baloxavir and reduced fitness in variants. In the poster session, we report the key nonclinical and clinical profiles of baloxavir.