On Oct. 9, 2020, Rigel Pharma announced enrollment of the first patients in a multicenter, Phase 2 trial to evaluate the safety of fostamatinib, Rigel’s oral spleen tyrosine kinase (SYK) inhibitor, for the treatment of hospitalized COVID-19 patients. The study was sponsored by the National Heart, Lung, and Blood Institute, in collaboration with Inovaﾮ Health System. Fostamatinib, marketed in the U.S. as TAVALISSEﾮ (fostamatinib disodium hexahydrate) tablets, is approved in the U.S. and Europe as a treatment for adult chronic immune thrombocytopenia (ITP).

The clinical trial is being conducted at the NIH Clinical Center in Bethesda, Maryland, the nation’slargest hospital devoted entirely to clinical research, and Inova Fairfax Hospital. 

his is a randomized, double-blind, placebo-controlled trial to evaluate the safety of fostamatinib for the treatment of hospitalized COVID-19 patients. The study will randomly assign fostamatinib or matched placebo (1:1) to approximately 60 evaluable patients who are a 5 to 7 on the 8-point ordinal scale (requiring supplemental oxygen via nasal canula or non-invasive ventilation, requiring mechanical ventilation or extracorporeal membrane oxygenation). Treatment will be administered orally twice daily for 14 days. There will be a follow-up period to day 60. The primary objective of this study is to evaluate the safety of fostamatinib compared to placebo for the treatment of hospitalized COVID-19 patients. The secondary objective will be to assess the early efficacy and clinically relevant measures of disease progression.

COVID-19 is the infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2).  SARS-CoV-2 primarily infects the upper and lower respiratory tract and can lead to acute respiratory distress syndrome (ARDS). Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock resulting in endothelial dysfunction and subsequently micro and macrovascular thrombosis.¹ Much of the underlying pathology of SARS-CoV-2 is thought to be secondary to a hyperinflammatory immune response associated with increased risk of thrombosis.²

SYK is involved in the intracellular signaling pathways of many different immune cells. Therefore, SYK inhibition may improve outcomes in patients with COVID-19 via inhibition of key Fc gamma receptor (FcγR) and c-type lectin receptor (CLR) mediated drivers of pathology, such as inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps (NETs) by neutrophils, and platelet aggregation. Furthermore, SYK inhibition in neutrophils and platelets may lead to decreased thromboinflammation, alleviating organ dysfunction in critically ill patients with COVID-19.