Pharmacokinetic and Pharmacodynamic Evaluation of Ravulizumab in Adults with Severe Coronavirus Disease 2019

• DOI: 10.1007/s40121-021-00425-7
• Publication Date: 2021-04-07T10:17:56Z
• Authors: Alanna C. McEneny...; Jonathan P. R. Mo...; Shamsah D. Kazani; Stephan R. Ortiz
• Keywords: Pharmacodynamics; Regimen

Terminal complement amplification is hypothesized to be a key contributor the clinical manifestations of severe coronavirus disease 2019 (COVID-19). Ravulizumab, humanized monoclonal antibody that binds with high affinity protein C5 and inhibits terminal activation, being evaluated as treatment for COVID-19-related pneumonia, acute lung injury, respiratory distress syndrome in an ongoing phase 3 randomized controlled trial (ALXN1210-COV-305). To address overactivation COVID-19 compared diseases which ravulizumab currently approved, modified dosing regimen was adopted. This analysis evaluates preliminary pharmacokinetic/pharmacodynamic data confirm regimen. Weight-based doses were administered on days 1, 5, 10, 15. Serum levels free measured before after administration any time day 22. Free < 0.5 μg/mL indicate complete inhibition. The pharmacokinetic target defined concentrations at end interval > 175 μg/mL, concentration above completely inhibited. Twenty-two patients included this evaluation. At baseline, mean 240 ± 67 μg/mL. In all individual timepoints first dose administered, remained High baseline observed contribute growing body evidence suggests marked by activation. Data from evaluation 22 show achieved immediate inhibition, can sustained up days. These support continued use dosage study. ClinicalTrials.gov identifier, NCT04369469 While many people have no or mild symptoms, small number become very sick require hospitalization intensive care units. One part their immune system, known complement, overreacts attacks lungs other organs. Researchers are looking way keep system attacking instead protecting it. Ravulizumab medication used do diseases. studied see if it reduce destructive deadly effects infection. evaluation, effectively reduced COVID-19.