In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in baloxavir vs. placebo group (p<0.05). In the phase 3 trial, the intention-to-treat infected population (n=1064), the median time to alleviation of symptoms was 53.7 hours with baloxavir vs. 80.2 hours with placebo (p<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 and phase 3 trial, respectively. The researchers suggest that because this treatment is inhibitory for influenza virus strains resistant to neuraminidase inhibitors or M2 ion-channel inhibitors, it could provide an option for patients with infections caused by such viruses.
According to an editorial, these studies should be viewed as a first step and the findings tempered by the need for data on baloxavir efficacy and safety through clinical trials involving patients with influenza who are most likely to benefit from antiviral treatment (persons at higher risk for influenza complications because of age, pregnancy, or chronic coexisting medical conditions). It adds that data are also needed on the clinical benefit of administering baloxavir more than 48 hours after illness onset to outpatients who are in a high-risk group and to patients of all ages who are hospitalized with severe influenza complications, including critical illness. Pharmacokinetic and pharmacodynamic data are also needed to inform appropriate dosing and to determine whether additional doses are beneficial in patients with severe influenza.
Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents. It was filed for approval under priority review in US in June 2018.