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BOSTON -- Fostamatinib (Tavalisse) added to standard care reduced the number of days on supplemental oxygen and improved clinical status in hospitalized patients with COVID-19, the phase III randomized FOCUS trial showed.

In patients who received fostamatinib in addition to standard treatment, the number of days on oxygen was reduced by an estimated mean of 2.8 days compared with those who received placebo and standard treatment (mean number of days on oxygen by day 29 4.8 vs 7.6, respectively; P=0.0136), reported Deepa Gotur, MD, of Houston Methodist and Weill Cornell Medical College.

Adding the spleen tyrosine kinase inhibitor also significantly improved patients' clinical status on the 8-point Ordinal scale by day 15, with a change from baseline of -2.8 versus -2.2 in the placebo group (P=0.0092), Gotur said during her presentation at the IDWeek annual meeting.

"The benefit of fostamatinib treatment appears to be especially evident in more severe patients," she noted. "Of the six patients with a baseline clinical score of 6, all three in the placebo group died, while all three in the fostamatinib group survived."

Fostamatinib-treated patients also had significantly fewer days in the intensive care unit compared with those in the placebo group (mean 0.8 vs 2.3; P=0.0753), and significantly more fostamatinib patients were alive and off supplemental oxygen at day 29 (85.1% vs 73.4%, respectively; P=0.0213) and at day 60 (85.1% vs. 71.9%; P=0.0271).

While there were numeric benefits in mortality in the fostamatinib group, those were not statistically significant.

Fostamatinib, which is FDA approved for the treatment of immune thrombocytopenia, is a potent anti-inflammatory that targets both pathogen-associated molecular patterns and damage-associated molecular patterns. Through these inflammatory pathways, fostamatinib exerts effects on mast cells, neutrophils, B cells, macrophages, and dendritic cells.

"Fostamatinib prevents the downward cascade leading to cytokine storm that leads to the hyperinflammation we see in patients with severe COVID-19," Gotur said. The drug has been shown to have beneficial effects on endothelial function and acute lung and kidney injury. It also reduces the risk of thrombosis by inhibiting platelet activation and "," which creates neutrophil extracellular traps.

The was conducted in the U.S., Mexico, Brazil, and Argentina from February 2021 to September 2022, and randomized 280 patients to 150-mg oral fostamatinib or matching placebo twice daily plus standard of care for 14 days. Mean age was 52.8, 72.5% were men, and 89.6% were white.

The patients were primarily a high-risk population; 56.8% had a body mass index over 30, 25.7% had a history of type 2 diabetes, 45.4% had a history of hypertension, and 9.3% had a history of cardiovascular disease.

On the 8-point Ordinal scale, 87.5% had a clinical status score of 5 at baseline. About three-quarters had already received some sort of COVID-19 treatment within 14 days prior to randomization, and 45% had been vaccinated against COVID, although Gotur did not specify levels of partial or complete coverage. During the trial, 91.5% received dexamethasone.

Adverse events occurred in 62% of those taking fostamatinib and 64.4% of those taking placebo. The most common adverse events in each group were liver enzyme abnormalities. Alanine aminotransferase was elevated in 9.3% and 10.4%, respectively, and aspartate aminotransferase in 7.1% and 4.4%.

Other adverse events of note included pneumonia (1.4% vs 5.9%), respiratory failure (2.9% vs 5.2%), anxiety (5.7% vs 3%), constipation (6.4% vs 8.1%), and diarrhea (4.3% vs 5.2%).

Fifteen patients died: six in the fostamatinib group and nine in the placebo group.