In patients with severe COVID-19 pneumonia and hyper-inflammation, mavrilimumab was associated with decreased mechanical ventilation and death compared with placebo. Moreover, this global randomised double-blind phase 2 trial demonstrated a beneficial safety profile of mavrilimumab over placebo.
The need for treatment alternatives in COVID-19 pneumonia is largely unmet. Mavrilimumab, a human monoclonal antibody blocking GM-CSF signalling, has shown clinical benefits in previous phase 2 trials investigating this population. In the current phase 2 trial, non-mechanically-ventilated severe COVID-19 patients with pneumonia and hyper-inflammation (n=114, mean age 57.1) were randomised to 1 of the 3 treatment arms: 6 mg/kg intravenous mavrilimumab (first week qd, thereafter qw), 10 mg/kg mavrilimumab, or placebo. The primary efficacy endpoint was the proportion of patients alive and without mechanical ventilation at day 29.
Dr Lara Pupim (Kiniksa Pharmaceutical Corp., USA) presented the results. On day 29, 86.7% of the patients in the mavrilimumab treatment arms were alive and without mechanical ventilation versus 74.4% of the patients in the placebo arm. The risk of death was 61% lower in mavrilimumab recipients and the risk of death or mechanical ventilation was reduced by 65%. In addition, the median time to a 2-point clinical improvement on the National Institute of Allergy and Infectious Diseases COVID-19 ordinal scale was respectively 7 days for mavrilimumab recipients and 11 days for the placebo group. The median time to return to room air was 7 days (mavrilimumab) versus 9 days (placebo).
No drug-related serious adverse events (AEs) occurred in the mavrilimumab arms. AEs were less common in mavrilimumab-treated patients and infections were more likely to occur in the placebo group (mavrilimumab 9.8–11.4% vs placebo 22.5%). Thrombotic events were only observed in the placebo arm. Finally, no apparent differences in efficacy or safety were registered between the 2 mavrilimumab treatment arms.
Pupim L, et al. Mavrilimumab Improves Outcomes in Phase 2 Trial in Non-Mechanically Ventilated Patients with Severe COVID-19 Pneumonia and Systemic Hyperinflammation. LB0001, EULAR 2021 Virtual Congress, 2-5 June.