medwireNews: Inhibition of granulocyte–macrophage-colony stimulating factor (GM-CSF) with mavrilimumab may represent a promising treatment option for patients with severe COVID-19 pneumonia and systemic hyperinflammation, suggest phase 2 study results.
Presenting the findings as a late-breaking abstract at the EULAR 2021 Virtual Congress, Lara Pupim (Kiniksa Pharmaceuticals Corp., Lexington, Massachusetts, USA) said that the efficacy and safety profiles of mavrilimumab have been demonstrated previously in phase 2 studies involving patients with rheumatoid arthritis and giant cell arteritis.
She explained that “GM-CSF is implicated in the mechanism of aberrant immune cell infiltration and activation in the lungs, and it may contribute to respiratory failure and death in patients with severe COVID-19 pneumonia and systemic hyperinflammation.”
Therefore, it was hypothesized that mavrilimumab, which “binds GM-CSF receptor alpha and downregulates inflammatory processes,” could “reduce infiltration of pathogenic cells into the lung and […] suppress inflammation in COVID-19 pneumonia,” she added.
Pupim and team’s trial involved two cohorts of hospitalized patients with COVID-19: nonventilated (cohort 1) and recently ventilated (cohort 2). The present analysis focused on cohort 1 and involved 114 patients with hypoxia and severe COVID-19 pneumonia from North and South America and South Africa, almost all of whom were receiving corticosteroids including dexamethasone. The average age was 57.1 years and 49% of participants had a BMI above 30 kg/m2.
At day 29, the proportion of patients alive and free of mechanical ventilation – the primary endpoint – was numerically higher among the 75 participants randomly assigned to receive a single intravenous administration of mavrilimumab 6 mg/kg or 10 mg/kg compared with the 39 given placebo, at 87% versus 74%. The between-group difference did not reach statistical significance, however.
When the probability of ventilation-free survival was evaluated over time, participants given mavrilimumab had a significant 65% lower risk for mechanical ventilation or death from day 0 to 29 relative to those given placebo.
The team also found that mortality rates at day 29 were numerically lower among mavrilimumab- versus placebo-treated patients (8 vs 21%), as was the median time to a 2-point clinical improvement on a COVID-19 ordinal scale (7 vs 11 days).
Pupim noted that there was “no apparent difference” in efficacy between the two different doses of mavrilimumab.
In terms of safety, she said that there were no drug-related serious adverse events in patients treated with mavrilimumab, and thrombotic events occurred in five patients in the placebo arm only.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group
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