Tocilizumab is an IgG1 class humanized monoclonal antibody targeting IL-6 receptor (IL-6R). IL-6 is a key cytokine involved in cytokine storm of severe COVID-19. Tocilizumab down-regulates IL-6 preventing fatal and permanent damage to vital organs, significantly preventing COVID-19 related mortality and morbidity. Therefore, this study aimed to compare the efficacy and safety of Tocilizumab (biosimilar) developed by Hetero Biopharma Ltd, India vs reference medicinal product (RMP)-Tocilizumab manufactured by Roche in cytokine storm of severe COVID-19 pneumonia.
This multicenter, randomized, double-blind, active-controlled study enrolled patients aged 18 to 65 years, with laboratory-confirmed, hospitalized, severe COVID-19 disease with elevated inflammatory markers not on mechanical ventilation. Patients were randomized (3:1 ratio) to receive either Test-Tocilizumab (Test) 8 mg/kg or RMP-Tocilizumab 8mg/kg, maximum 800mg, administered once on day 1. The primary endpoint was the cumulative proportion of patients requiring mechanical ventilation by Day 14. Secondary endpoints included 28 day mortality rate, proportion of patients with a 2-point decrease in WHO ordinal scale, time to clinical failure (death or required mechanical ventilation or withdrawn), change in inflammatory markers (CRP, IL-6, Ferritin and D-dimer) and duration of hospital stay in days. Safety endpoints included the incidence of adverse events; the proportion of patients discontinued the study due to adverse events and the incidence of any post-treatment bacterial and/or fungal infection.
Out of 211 patients screened, 172 patients were randomized (131 to Test and 41 to RMP) to receive Tocilizumab 8mg/kg. Patients were similar in both groups at baseline in terms of age, gender, weight etc. Fourteen (10.69%) patients in Test and 5 (12.20%) patients in RMP progressed to mechanical ventilation by Day 14 (p=0.7789). Overall, 9 (7.83%) patients died in Test vs 5 (13.16%) in RMP during 28 days follow up (p=0.3382). Clinical improvement was seen 62.60% and 77.10% vs 53.66% and 73.17% in Test vs RMP at day 14 and 28 respectively. The time to clinical failure was 6 vs 5 days and time to clinical improvement was 11 vs 11.5 days. Hospitalization duration was 12.9 versus 13.8 days in the Test and RMP. ARDS, Insomnia and Pain were most commonly reported adverse events.
Tocilizumab biosimilar is comparable with RMP-Tocilizumab in preventing mechanical ventilation in severe COVID19 pneumonia patients