Favipiravir Not Beneficial for Treating Early Symptomatic COVID-19

High-dose favipiravir is not associated with antiviral activity in early symptomatic COVID-19 infection, according to study findings published in BMC Infectious Diseases.

Researchers reported findings from PLATCOV (ClinicalTrials.gov Identifier: NCT05041907), an ongoing, phase 2, open-label, randomized controlled adaptive platform trial that evaluated the in vivo antiviral activity of favipiravir in previously healthy adults aged 18 to 50 years with early symptomatic COVID-19.

Participants who were allocated to favipiravir received 1800 mg at the start of treatment an additional 1800 mg 12 hours later. Afterward, the patients were administered 800 mg twice daily for 6 days for a total of 13.2 g over 7 days. The primary outcome was viral clearance rate.

The analyses were conducted in a prespecified modified intention-to-treat (mITT) population of patients who had at least 3 days of follow-up data. The mITT population included 114 patients randomly assigned to favipiravir and 126 patients randomly assigned to no study drug. The overall cohort had a mean (SD) age of 30.1 (7.4) years, and 63% were female.

Viral clearance rates were estimated with a linear mixed-effects model fitted to polymerase chain reaction data taken up to 7 days after randomization in the mITT population (4318 swabs in 240 patients, of which 3839 were greater than the lower limit of quantification, 89%).

In a sensitivity analysis, a nonlinear model found no evidence of a difference in viral clearance rates between patients who received favipiravir and those who had no study drug (mean difference: –1%; 95% CI, –14% to 14%). The posterior probability was 0.97 that the effect was less than the pre-specified futility margin of 12.5%. The nonlinear model demonstrated comparable estimates (mean difference: –5%; 95% CI, –14% to 6%; probability less than 12.0% equal to 1).

Patients who received favipiravir had an estimated median viral clearance half-life of 16.6 hours (range, 6.7-48.0), and those who received no study drug had an estimated median viral clearance half-life of 15.7 hours (range, 3.4-42.1) in the linear model.

The oropharyngeal swabbing procedures and treatment were well-tolerated, with 3 serious adverse events occurring in the no-study-drug arm and 2 in the favipiravir arm. These events resulted in the secondary endpoint of clinical deterioration leading to hospitalization for medical reasons. No treatment-related serious adverse events were observed.

The main study limitation was the open-label design, which may have resulted in more withdrawals in the no-study-drug arm.

“This comparative in vivo pharmacodynamic assessment conducted in ‘low risk’ adults with early symptomatic COVID-19 infections shows that favipiravir, given at relatively high oral doses, does not have measurable antiviral activity in vivo and is, therefore, very unlikely to be clinically beneficial,” the study authors concluded.

This article originally appeared on Pulmonology Advisor