12 October 2020 - - The first patients have been enrolled in a multicenter, Phase 2 trial to evaluate the safety of fostamatinib, US-based Rigel Pharmaceuticals, Inc's (NASDAQ: RIGL) oral spleen tyrosine kinase inhibitor, for the treatment of hospitalized COVID-19 patients, the company said.

The study is sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, in collaboration with Inova Health System.

Fostamatinib, marketed in the US as TAVALISSE (fostamatinib disodium hexahydrate) tablets, is approved in the US and Europe as a treatment for adult chronic immune thrombocytopenia.

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

This 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 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.

Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock resulting in endothelial dysfunction and subsequently micro and macrovascular thrombosis.

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.

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 and c-type lectin receptor mediated drivers of pathology, such as inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps 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.

Rigel Pharmaceuticals, Inc. is a biotechnology company dedicated to discovering, developing and providing novel small molecule drugs that significantly improve the lives of patients with immune and hematologic disorders, cancer and rare diseases.

Rigel's research focuses on signaling pathways that are critical to disease mechanisms.

The company's first FDA approved product is TAVALISSE (fostamatinib disodium hexahydrate) tablets, the only oral spleen tyrosine kinase inhibitor, for the treatment of adult patients with chronic immune thrombocytopenia who have had an insufficient response to a previous treatment.

The product has been approved by the European Commission for the treatment of chronic immune thrombocytopenia in adult patients who are refractory to other treatments and is marketed in Europe under the name Tavlesse (fostamatinib).

Fostamatinib6 is currently being studied in a Phase 3 trial for the treatment of warm autoimmune hemolytic anemia ; a NIH/NHLBI-Sponsored Phase 2 trial for the treatment of hospitalized COVID-19 patients, in collaboration with Inova Health System; and a Phase 2 trial for the treatment of COVID-19 pneumonia being conducted by Imperial College London.

Rigel's other clinical programs include a completed Phase 1 study of R8356, a proprietary molecule from its interleukin receptor associated kinase inhibitor program, and an ongoing Phase 1 study of R5526, a proprietary molecule from its receptor-interacting protein kinase inhibitor program.

In addition, Rigel has product candidates in clinical development with partners AstraZeneca, BerGenBio ASA, and Daiichi Sankyo.