Findings from a discontinued clinical trial of favipiravir in high-risk patients with early-onset COVID-19
Satoshi Iwata, Osamu Kobayashi, Kazuyoshi Kurashima, Yohei Doi, Hiroyuki Kunishima, Masaharu Shinkai, Kenji Tsushima, Masaya Yamato, Akira Kano, Makoto Hibino, Takahiro Yamatake, Tsutomu Sakurai, Takashi Ogura
Journal of Infection and Chemotherapy, doi:10.1016/j.jiac.2023.10.010
Introduction: Favipiravir terminates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. Accordingly, early administration of favipiravir to SARS-CoV-2-infected coronavirus disease 2019 (COVID-19) patients may be expected to suppress disease progression. Methods: A randomized double-blind placebo-controlled trial was conducted to demonstrate efficacy of favipiravir in reducing disease progression in patients with mild COVID-19. The participants were unvaccinated patients with comorbidities and at risk of progression to severe disease. Patients were enrolled within 72 hours of disease onset and randomized to receive either favipiravir (1800 mg/dose on Day 1 followed by 800 mg/dose) or matching placebo twice daily for 10 days. The primary endpoint was the proportion of patients requiring oxygen therapy within 28 days of randomization.
Results: The trial was discontinued after enrolling 84 patients due to slower than anticipated enrollment caused by rapid uptake of SARS-CoV-2-vaccines and the emergence of the Omicron variant. Results from the 84 patients demonstrated no significant difference in all clinical outcomes. In post-hoc analyses, favipiravir treatment showed higher efficacy in patients within 48 hours of onset. No deaths or severe adverse events were documented in the favipiravir group. Plasma concentrations of favipiravir from Day 2 onward were maintained above 40 μg/mL.
Conclusions: Conducting clinical trials for pathogens like SARS-CoV-2 that rapidly accumulate mutations leading to altered disease characteristics carries significant risks unless it can be done in a short period. Therefore, it would be important to prepare the comprehensive clinical trial platform that can appropriately and promptly evaluate drugs even under a pandemic.
Declaration of competing interest TY and TS are employees of the sponsor. SI reports consulting fees from Fujifilm Toyama Chemical, and Meiji Seika Pharma; lecture fees from Pfizer, and Gilead Sciences. YD reports consulting fees from Fujifilm Toyama Chemical, Shionogi, GSK, Gilead Sciences, and Moderna. MS reports consulting fees from Genova Inc., Shionogi, Ono Pharmaceutical, AstraZeneca, Pfizer, Chugai, and Fujitsu; lecture fees from Fujifilm Toyama Chemical. OK, HK, and KT report consulting fee from Fujifilm Toyama Chemical. KK, MY, AK, and TO report lecture fee from Fujifilm Toyama Chemical. J o u r n a l P r e -p r o o f
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