A Randomised trial of anti-GM-CSF Otilimab in severe COVID-19 pneumonia (OSCAR)
Pulmonary/Critical Care Medicine
Abstract BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of coronavirus disease 2019 (COVID-19).
Methods: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure, and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28.
Results: In Part 1 (N=806 randomised 1:1 otilimab:placebo), 71% of otilimab-treated patients were alive and free of respiratory failure at Day 28 versus 67% who received placebo; the model-adjusted difference of 5.3% was not statistically significant (95% CI -0.8, 11.4; p=0.09). A nominally significant model-adjusted difference of 19.1% (95% CI 5.2, 33.1; p=0.009) was observed in the predefined 70-79 years subgroup, but this was not confirmed in Part 2 (N=350 randomised) where the model-adjusted difference was 0.9% (95% CI -9.3, 11.2; p=0.86). Compared with placebo, otilimab resulted in lower serum concentrations of key inflammatory markers, including the putative pharmacodynamic biomarker CCL17, indicative of GM-CSF pathway blockade. Adverse events were comparable between groups and consistent with severe COVID-19.
Conclusions: There was no significant difference in the proportion of patients alive and free of respiratory failure at Day 28. However, despite the lack of clinical benefit, a reduction in inflammatory markers was observed with otilimab, in addition to an acceptable safety profile.
Patel J, Bass D, Beishuizen A, Bocca Ruiz X, Boughanmi H, Cahn A, Colombo H, Criner GJ, Davy K, de-Miguel-Díez J, Doreski PA, Fernandes S, François B, Gupta A, Hanrott K, Hatlen T, Inman D, Isaacs JD, Jarvis E, Kostina N, Kropotina T, Lacherade JC, Lakshminarayanan D, Martinez-Ayala P, McEvoy C, Meziani F, Monchi M, Mukherjee S, Muñoz-Bermúdez R, Neisen J, O'Shea C, Plantefeve G, Schifano L, Schwab LE, Shahid Z, Shirano M, Smith JE, Sprinz E, Summers C, Terzi N, Tidswell MA, Trefilova Y, Williamson R, Wyncoll D, Layton M. A Randomised trial of anti-GM-CSF Otilimab in severe COVID-19 pneumonia (OSCAR). Eur Respir J. 2022 Oct 13:2101870. doi: 10.1183/13993003.01870-2021. Epub ahead of print.