A Randomized Trial of Otilimab in Severe COVID-19 Pneumonia (OSCAR)

Patel, J.; Beishuizen, A.; Bocca Ruiz, X.; Boughanmi, H.; Cahn, A.; Criner, G. J.; Davy, K.; de-Miguel-Diez, J.; Fernandes, S.; Francois, B.; Gupta, A.; Hanrott, K.; Hatlen, T.; Inman, D.; Isaacs, J. D.; Jarvis, E.; Kostina, N.; Lacherade, J.-C.; Martinez-Ayala, P.; McEvoy, C.; Munoz-Bermudez, R.; Neisen, J.; Plantefeve, G.; Schifano, L.; Schwab, L.; Shahid, Z.; Shirano, M.; Smith, J. E.; Sprinz, E.; Summers, C.; Terzi, N.; Tidswell, M. A.; Williamson, R.; Wyncoll, D.; Layton, M.

BACKGROUND Increasing age is a risk factor for COVID-19 severity and mortality; emerging science implicates GM-CSF and dysregulated myeloid cell responses in the pathophysiology of severe COVID-19. METHODS We conducted a large, global, double-blind, randomized, placebo-controlled study evaluating a single 90 mg infusion of otilimab (human anti-GM-CSF monoclonal) plus standard of care in adults hospitalized with severe COVID-19 respiratory failure and systemic inflammation, stratified by age and clinical status. Primary outcome was the proportion of patients alive and free of respiratory failure at Day 28; secondary endpoints included all-cause mortality at Day 60. RESULTS Overall, 806 patients were randomized (1:1); 71% of patients receiving otilimab were alive and free of respiratory failure at Day 28 versus 67% receiving placebo, although this did not reach statistical significance (model-adjusted difference 5.3% [95% CI 0.8, 11.4]; p=0.09). However, there was a benefit in the pre-defined [≥]70-year age group (model-adjusted difference 19.1% [95% CI 5.2, 33.1]; nominal p=0.009); these patients also had a reduction of 14.4% (95% CI 0.9, 27.9%; nominal p=0.04) in model-adjusted all-cause mortality at Day 60. Safety findings were comparable between otilimab and placebo, and consistent with severe COVID-19. CONCLUSIONS Although not statistically significant in the overall population, otilimab demonstrated a substantial benefit in patients aged [≥]70, possibly reflecting a population that could benefit from therapeutic blocking of GM-CSF in severe COVID-19 where myeloid cell dysregulation is predominant. These findings are being confirmed in a further cohort of patients aged [≥]70 in Part 2 of this study. (ClinicalTrials.gov number: NCT04376684).