Influence of demographics and dosing on COVID-19 outcomes and Favipiravir efficacy

<bold>Introduction:</bold> Favipiravir was found to be non-efficacious in treating patients with COVID-19, with post hoc analysis revealing a beneficial effect only in those aged <60. Understanding the relationship between demographics, pharmacodynamics and disease trajectories is crucial in determining future pandemic preparedness. <bold>Hypothesis:</bold> Patient demographics influence favipiravir response. Tailored dosing based on demographics may enhance efficacy. <bold>Aims:</bold> To evaluate demographic impacts on COVID-19 outcomes and favipiravir response, and to assess favipiravir pharmacodynamics in hospitalised patients. <bold>Methods:</bold> Demographic data from hospitalised COVID-19 patients in the Pioneer trial, who received favipiravir (n=205), or standard care (n=228), were analysed. Plasma favipiravir concentrations were measured between days 5-10 post treatment initiation. NCT: 04373733. <bold>Results:</bold> Age, gender and comorbidity impacted favipiravir efficacy. For men, 28 day survival remained consistent regardless of treatment, while women saw an 8% increase in survival with favipiravir. Male comorbid patients had increased mortality relative to females (p=0.04), with endocrine and renal comorbidities specifically worsening male survival (p=0.005). Comorbidity worsened survival of favipiravir recipients (p=0.04), but not standard care (p=0.23). 17% (29 of n=174) reached target plasma concentrations. This subgroup exhibited improved primary endpoint attainment (p=0.07) and mortality (p=0.11) relative to standard care. <bold>Conclusion:</bold> Administering a higher dose of favipiravir or tailoring dosage considering patient heterogeneity may enhance COVID-19 treatment. Future work will explore links between underdosing and patient demographics.