A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR)
Jatin Patel, Damon Bass, Albertus Beishuizen, Xavier Bocca Ruiz, Hatem Boughanmi, Anthony Cahn, Hugo Colombo, Gerard J. Criner, Katherine Davy, Javier de Miguel‐Díez, Pablo Alexis Doreski, Sofia Fernandes, Bruno François, Anubha Gupta, Kate Hanrott, Timothy Hatlen, Dave Inman, John D. Isaacs, Emily Jarvis, N. E. Kostina, Tatiana Kropotina, Jean-Claude Lachérade, Divya Lakshminarayanan, Pedro Martínez-Ayala, Charlene McEvoy, Ferhat Meziani, Mehran Monchi, Sumanta Mukherjee, Rosana Muñoz-Bermúdez, Jessica Neisen, Ciara O’Shea, Gaëtan Plantefève, Lorrie Schifano, Lee Schwab, Zainab Shahid, Michinori Shirano, Julia E. Smith, Eduardo Sprinz, Charlotte Summers, Nicolas Terzi, Mark Tidswell, Yuliya Trefilova, R. Williamson, Duncan Wyncoll, Mark Layton
Abstract
BACKGROUND: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of 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: 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 CC chemokine ligand 17, 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.