In patients hospitalized for COVID-19 who receive oxygen, the addition of fostamatinib, a novel spleen tyrosine kinase inhibitor, to standard of care (SOC) therapy was associated with significantly fewer days on oxygen therapy compared with SOC alone. Fostamatinib was also safe and well-tolerated by these patients, according to research findings published in Clinical Infectious Diseases.
The double-blind clinical trial (ClinicalTrials.gov Identifier: NCT04579393) included 59 adult patients (mean age, 55.6 years) hospitalized for COVID-19 who required supplemental oxygen. In the study, all patients received SOC, which consisted of predominantly remdesivir and corticosteroids.
Patients were randomly assigned to receive either 150 mg fostamatinib (n=30) or placebo (n=29) in addition to the SOC regimen for a total of 14 days. Treatment was continued regardless of whether the patients remained in the hospital or were discharged before the 14-day follow-up.
Approximately 39% of patients had moderate disease at baseline, while 61% had severe or critical disease. The median duration from symptom onset was 10 days. In addition to SOC, 42% of patients also received convalescent plasma. The overall mean body mass index (BMI) was 32.3 kg/m2, which falls over the BMI classification for obesity. The majority of patients had coexisting conditions, with 25.4% having 1 condition and 55.9% having 2 or more conditions.
Serious adverse events (AEs) occurred in 9 patients. There was no significant difference between the fostamatinib arm and the placebo group in terms of the rate of serious AEs (10.5% vs 22.0%, respectively; P =.2). Worsening hypoxia was the most frequently reported serious AE (n=4). Only 3.3% of patients in the fostamatinib group had a serious AE classified as respiratory-related or death, whereas 18.5% of patients had a similar event (P =.08).
All deaths (n=3) occurred in the placebo arm. At 28 days following randomization, Kaplan-Meier estimates of mortality were 11.1% for placebo and 0% for fostamatinib (P =.07). In those enrolled with a baseline ordinal score of 6 or 7, there was a trend toward reduced mortality in patients with severe/critical disease in the fostamatinib arm compared with the placebo group (0% vs 20%, respectively; P =.049).
At day 15, the mean change in ordinal score was significantly greater in the fostamatinib arm vs the placebo group (-3.6±0.3 vs -2.6±0.4, respectively; P =.035), with the difference being most pronounced in patients with severe/critical disease (P <.05).
The median duration of intensive care unit stay was 3 days in the fostamatinib arm vs 7 days in the placebo group (P =.07). By day 15, a significantly greater proportion of patients assigned to fostamatinib with severe/critical disease did not require any supplemental oxygen (57.9% vs 20%; P =.016). The median duration of oxygen therapy through day 29 was also significantly shorter for the fostamatinib group (10 vs 28 days; P =.027).
The investigators noted changes in multiple inflammatory biomarkers during treatment that favored fostamatinib. These markers included C-reactive protein (CRP), D-dimer, fibrinogen, and ferritin levels. The trends towards improvement for these biomarkers were more noticeable in those with severe/critical disease.
A limitation of this study included its small sample. The researchers added that the study was underpowered for both efficacy outcomes and subgroup analysis. Given the limitation, the researchers wrote that “larger confirmatory trials are needed to further evaluate the efficacy of fostamatinib in COVID-19.”
This research was funded by the US National Institutes of Health, which has a research collaboration with a pharmaceutical company with a commercial interest in fostamatinib. Please see the original reference for full disclosure information.
Strich JR, Tian X, Samour M, et al. Fostamatinib for the treatment of hospitalized adults with COVD-19 A randomized trial. Clin Infect Dis. Published online September 1, 2021. doi:10.1093/cid/ciab732