A single-dose of a novel influenza antiviral out-performed placebo in alleviating influenza symptoms and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza.
That’s according to a report in the New England Journal of Medicine which also found that use of baloxavir marboxil was without evident safety concerns.
Influenza virus. Source
The antiviral, approved by the U.S. Food and Drug Administration as Xofluza, is a selective inhibitor of influenza cap-dependent endonuclease which has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.
An international study team led by researchers from the University of Virginia School of Medicine conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza.
Using a dose-ranging (10 to 40 mg) placebo-controlled trial, the investigators conducted a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016–2017 season. In comparison, the dose of oseltamivir was 75 mg twice daily for 5 days.
Defined as the primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.
In the phase 2 trial, results indicated that median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05).
The phase 3 trial had an intention-to-treat infected population of 1,064 participants, and 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. Researchers reported that the median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001).
The time to alleviation of symptoms was similar with baloxavir and oseltamivir, although baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than either placebo or oseltamivir.
Adverse events were reported in a slightly lower percentage of baloxavir recipients, 20.7%, compared to 24.6% of placebo recipients and 24.8% of oseltamivir recipients.
The study team also pointed out that 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 trial and phase 3 trial, respectively.
“Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza,” study authors concluded. “Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed.”