Baloxavir marboxil in Japanese patients with seasonal influenza: Dose response and virus type/subtype outcomes from a randomized phase 2 study

Baloxavir marboxil (baloxavir) is an antiviral drug that inhibits the viral "cap-snatching" step in virus RNA transcription initiation. In Phase 2 study, baloxavir significantly shortend the time to alleviation of symptoms (TTAS) and showed significantly greater reduction in influenza virus titer compared with placebo. This provides additional outcomes including efficacy against virus types/subtypes and pharmacokinetic/pharmacodynamic (PK/PD) analysis. Subgroup analyses by virus types/subtype were conducted for the primary and key secondary endpoints. Blood samples were collected totally at 2 to 5 points including Day 2 after baloxavir dosing. PK/PD analyses were conducted for TTAS and change in virus titer using the liner model and the Emax model, respectively. The median TTAS in each baloxavir dose group was significantly shorter than in the placebo group for patients with A/H1N1pdm virus, and was numerically shorter than the placebo group for patients with A/H3N2 and type B virus. Baloxavir significantly reduced virus titer within 1 day after treatment: for A/H1N1pdm, A/H3N2, and B virus, all 3 doses of baloxavir marboxil reduced virus titer on Day 2 to a greater extent than placebo. No clear PK/PD relationships were found for the TTAS, but the larger reduction in virus titer was observed in increasing C24. These results support that baloxavir marboxil will be effective against a range of virus types/subtypes.