Data from NIH/NHLBI-sponsored phase II trial of fostamatinib in hospitalized COVID-19 patients is published in Clinical Infectious Diseases journal. Rigel Pharma

The results from the 59 patient Phase II trial demonstrated that the addition of fostamatinib to standard of care (SOC), which included the antiviral remdesivir and the steroid dexamethasone, was well tolerated and associated with clinically meaningful improvement in clinical outcomes in hospitalized COVID-19 patients who required supplemental oxygen. While the study was not powered to test clinical efficacy, numerous prespecified secondary endpoints consistently favored fostamatinib, including mortality, time to sustained recovery, change in ordinal scale assessment, number of days on oxygen, and number of days in the ICU, suggesting that fostamatinib may provide an additional therapeutic benefit compared to current SOC alone.

Key findings within the fostamatinib Phase II trial include: i. The study met the primary endpoint showing fostamatinib did not increase the incidence of serious adverse events (SAEs) compared with placebo. ii. The overall incidence of SAEs by Day 29 was approximately 50% less in the fostamatinib group (10.5%) compared with the placebo group (22.0%) (p=0.2) .iii. The most frequent SAE reported by Day 29 was hypoxia, occurring in 1 patient receiving fostamatinib and 3 patients receiving placebo. iv. At Day 29, in the overall population there were zero deaths in the fostamatinib group compared to 3 in the placebo group (p=0.07). In more severe patients (ordinal scale 6 or 7), the difference was 0/19 patients in the fostamatinib group compared to 3/17 patients in the placebo group (p=0.049) , v. There were 4 intubated patients in the trial on mechanical ventilation (ordinal scale 7) upon enrollment with 2 patients randomized to each treatment group. Both patients in the fostamatinib group were extubated and discharged from the hospital, while both patients in the placebo group deceased. vi. The median number of days in the ICU was reduced by 4 days, from 7 days (IQR 2-10) in the placebo group to 3 days (IQR 2-5) in the fostamatinib group (p=0.07). vii. The median number of days on oxygen was 8 (IQR 5-10) in the fostamatinib group compared to 20 (IQR 14-27) in the placebo group (p=0.2). The difference was even greater in more severe patients with the fostamatinib group at 10 days compared to placebo at 28 days (p=0.027). viii. At Day 15, 65.5% of patients were free of supplemental oxygen in the fostamatinib group compared to 39.9% in the placebo group (p=0.08). In more severe patients, the difference was 57.9% compared to 20% (p=0.016) ix. Fostamatinib was superior to placebo in accelerating improvement in clinical status from baseline by Day 15 (mean change -3.6 + 0.3 vs. -2.6 + 0.4; p=0.035) using ordinal scale assessments. x. The median time to recovery was 8 days in both groups. The greatest benefits were observed in more severe patients where the median time to recovery was reduced from 13 days (IQR 11-19) in the placebo group to 10 days (IQR 6-13) in the fostamatinib group. Despite general SOC use of both steroids and remdesivir in all 59 patients, there was a consistently greater reduction in NETosis and other inflammatory biomarkers (CRP, Ferritin, D-Dimer, Fibrinogen) in the fostamatinib group compared to the placebo group.

See- " Fostamatinib for the treatment of hospitalized adults with COVD-19 A randomized trial"; Jeffrey R Strich et al. Clinical Infectious Diseases, ciab732, https://doi.org/10.1093/cid/ciab732 Published: 01 September 2021.