Fostamatinib

The FOCUS trial, enrolling more severely ill patients, found that fostamatinib significantly reduced days on supplemental oxygen compared with placebo. Evidence from multiple trials suggests fostamatinib may confer greater benefit at more advanced disease stages. Despite plausible biological rationale, MATIS found no benefit from fostamatinib, possibly because enrolled patients were too mildly ill, the dose was suboptimal, or the duration insufficient. Fostamatinib inhibits the SYK pathway, which is activated by C-type lectin receptors, C-type lectin-like receptors, and Fc receptors. SYK modulates cytokine secretion and promotes macrophage and monocyte influx into the lung, contributing to both the hyperinflammatory state and long-term lung damage. Fostamatinib caused a statistically significant elevation of serum creatinine compared with standard of care.