Blocking EGFR with nimotuzumab: A novel strategy for COVID-19 treatment
Keywords:
Nimotuzumab, COVID-19, SARS-CoV2, inflammation, fibrosis, EGFR, monoclonal antibodyAbstract
Introduction: Lung injury and STAT1 deficit can induce EGFR overexpression in SARS-CoV2 infected cells.
Methods: Considering the role of EGFR in inflammation and fibrosis, a Phase I/II trial was done to evaluate the safety and preliminary effect of nimotuzumab, a humanized anti-EGFR antibody, in severe and high-risk moderate patients with COVID-19. Patients were able to receive other drugs included in the national protocol. Treatment consisted on nimotuzumab intravenous infusions, administered every 72 hours. Before launching the study, EGFR expression was confirmed by immunohistochemistry in 20 lung samples from COVID-19 deceased subjects.
Results: They were included forty-one patients (31 severe/10 moderate) in the trial. The median age was 62 years and the main comorbidities were hypertension, diabetes, cardiovascular disease and obesity. Seven patients received one dose of nimotuzumab, 29 received 2 infusions while 5 subjects required 3 doses. The antibody was very safe. There were only 4 related adverse events in 2 subjects. Eight patients required invasive mechanical ventilation. The 14-day recovery rate was 82,9%. 90% in moderate patients and 80,64 % in severe patients. Inflammatory markers decreased overtime and interleukin-6 concentration diminished from 46,5 pg/ml to 14,51 pg/ml at day 7. None of the evaluated patients showed signs of fibrosis in the follow-up evaluation. After the use of nimotuzumab in 1,536 patients in the real-world scenario, a high recovery rate was achieved in severe and moderate patients (89,4% and 79.4%, respectively), which compares very favorably with the phase I/II trial data.
Conclusions: our results suggest that nimotuzumab is a safe antibody that can reduce inflammation and avoid fibrosis in severe and moderate COVID-19 patients at high risk of aggravation.
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