Hayden FG, et al. – Researchers assessed the efficacy of baloxavir marboxil, a selective inhibitor of influenza cap-dependent endonuclease, for the treatment of uncomplicated influenza in adults and adolescents. Findings suggested that single-dose baloxavir marboxil was safe and superior to placebo in alleviating influenza symptoms, and was superior to oseltamivir and placebo in reducing the viral load 1 day following initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir marboxil following treatment was also reported.

Methods

• Two randomized, double-blind, controlled trials were conducted, enrolling otherwise healthy outpatients with acute uncomplicated influenza.
• During the 2016–2017 season, following a dose-ranging (10 mg to 40 mg), placebo-controlled trial, a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir marboxil (40 mg or 80 mg) in patients aged 12 to 64 years was conducted.
• Oseltamivir 75 mg was administered twice daily for 5 days.
• The time to alleviation of influenza symptoms in the intention-to-treat infected population was the primary efficacy end point.

Results

• In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir marboxil groups vs the placebo group (P < 0.05).
• In the phase 3 trial, 1,064 patients were included in the intention-to-treat infected population; influenza A(H3N2) infection was observed in 84.8% to 88.1% of patients in each group.
• With baloxavir marboxil treatment, the median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI]: 49.5–58.5) vs 80.2 hours (95% CI: 72.6–87.1) with placebo (P < 0.001).
• With baloxavir marboxil and oseltamivir, time to alleviation of symptoms was similar.
• Baloxavir marboxil was associated with greater reductions in viral load 1 day following initiation of the regimen vs placebo or oseltamivir.
• Of those treated with baloxavir marboxil, adverse events (AEs) were observed in 20.7% of recipients; in the placebo and oseltamivir groups, AEs were reported in 24.6% and 24.8% of recipients, respectively.
• Of those treated with baloxavir marboxil in the phase 2 and 3 trials, emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir marboxil occurred in 2.2% and 9.7% of recipients, respectively.