Favipiravir may improve severe COVID-19 recovery, ventilator-free survival in younger patients
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Treatment with oral favipiravir had a beneficial effect on recovery and mechanical ventilation-free survival among patients younger than 60 years who were hospitalized with COVID-19, researchers reported.
Favipiravir (Toyama Chemical) is a pyrazine carboxamide-derived, nucleic acid analogue that targets the ribonucleic acid (RNA)-dependent RNA polymerase utilized in viral RNA synthesis. Before the current PIONEER trial, favipiravir was being investigated in the U.S. and Japan for uncomplicated influenza, Christopher M. Orton, MD, consultant respiratory physician at Royal Brompton Hospital, London, said during a presentation at the European Respiratory Society International Congress.
PIONEER was a prospective, open-label, multicenter, randomized controlled trial that included 499 patients (median age, 58.9 years; 61% men) from the U.K., Brazil and Mexico who were admitted to the hospital with proven or suspected COVID-19 from May 2020 to May 2021. Patients were randomly assigned to favipiravir (n = 251) or standard care (n = 248). The treatment period was 10 days; patients received favipiravir 1,800 mg twice daily on day 1 and then decreased to 800 mg twice daily for the remaining days.
The primary outcome was time to a 2-point improvement in WHO ordinal scale or discharge, whichever occurred first. Secondary outcomes focused on mortality and health care resource utilization.
Twenty-six patients died and 214 patients recovered within 28 days of treatment in the favipiravir group compared with 34 deaths and 203 recovered patients in the standard care group.
Researchers reported no significant difference in the types of recovery between the two groups. However, when they analyzed patients aged younger than 60 years, there was significant improvement in the speed to recovery on day 4 (P = .03), but these results were not identified among patients aged at least 60 years.
Regarding survival and mechanical ventilation-free survival, researchers observed no significant differences between the groups. However, when they analyzed patients aged younger than 60 years, researchers observed a greater numerical difference in deaths, with an approximate 50% reduction and a significant difference in mechanical ventilation-free survival (P = .02). Patients aged at least 60 years did not have such effects with favipiravir, according to the results.
“Oral favipiravir did not improve prespecified outcomes in patients hospitalized with COVID-19. However, we have demonstrated that there may be a beneficial effect on recovery and mechanical ventilation-free survival in patients under the age of 60,” Orton said. “... We certainly feel that wider evaluation of antiviral medications and potentially looking back at the data that’s already out there to see the age-stratified effects ... [is needed] ... and the potential for combination therapy should be considered in COVID-19.””