COVID-19

TAVALISSE® ​(fostamatinib disodium hexahydrate) is a selective, oral spleen tyrosine kinase (SYK) inhibitor being evaluated in three clinical trials for the treatment of hospitalized patients with COVID-19*.

In May 2018,​ TAVALISSE was approved by the U.S. Food and Drug Administration (FDA) for use in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

*TAVALISSE® (fostamatinib disodium hexahydrate) is not FDA-approved for use in COVID-19.

NIH/NHLBI Phase 2 Clinical Trial Design

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH), in collaboration with Inova Health System, has completed enrollment of a randomized, double-blind, placebo-controlled Phase 2 clinical trial in fifty-nine hospitalized patients with COVID-19.

NIH/NHLBI Phase 2 Clinical Trial

1Standard of care includes any treatments currently in use to treat the underlying disease, or comorbidities associated with COVID-19 (eg, remdesivir).

ICL (MATIS) Phase 2 Clinical Trial

Imperial College London (ICL) is enrolling a two-stage, randomized, open label, controlled Phase 2 clinical trial, also known as MATIS, in hospitalized patients with COVID-19.

ICL (MATIS) Phase 2 Clinical Trial Design

1Standard of care includes any treatments currently in use to treat the underlying disease, or comorbidities associated with COVID-19 (eg, dexamethasone).

Rigel Phase 3 Clinical Trial

Rigel is enrolling a randomized, double-blind, placebo-controlled, adaptive Phase 3 clinical trial in hospitalized patients with COVID-19. Rigel was awarded $16.5 million by the U.S. Department of Defense to support funding of this trial.

Rigel Phase 3 Clinical Trial

1Standard of care includes any treatments currently in use to treat the underlying disease, or comorbidities associated with COVID-19 (eg, remdesivir).

 

Coronavirus Disease 2019 (COVID-19)

COVID-19 is an 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 (FcyR) and c-type lectin receptor (CLR) mediated drivers of pathology such as pro-inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps (NETs) by neutrophils, and platelet aggregation.3,4,5 Furthermore, SYK inhibition in neutrophils and platelets may lead to decreased thromboinflammation, alleviating organ dysfunction in critically ill patients with COVID-19.


The Journal of Infectious Diseases (JID) published research in December 2020 from the NIH which demonstrated that R406, the active metabolite of fostamatinib, was able to inhibit NETosis ex vivo in donor plasma from patients with COVID-19. NETosis is a unique type of cell death resulting in the release of neutrophil extracellular traps (NETs). NETs contribute to thromboinflammation and have been associated with mortality in COVID-19. These data provide insights for how fostamatinib may mitigate neutrophil-associated mechanisms contributing to COVID-19 immunopathogenesis.6
 

Fostamatinib Inhibits NETosis Induced by Plasma from Severly Ill COVID-19 Patients

For product related questions or Medical Inquiries:

Please contact 1-800-983-1329 or email us at producthelp@rigel.com

For questions related to product access:

Please contact RIGEL ONECARE at 1-833-RIGELOC (1-833-744-3562) or 650-449-8646

References:

  1. Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J Med 2020
  2. Becker RC. COVID-19 Update: COVID-19 associated coagulopathy. Journal of Thrombosis and Thrombolysis May 15, 2020. DOI: https://doi.org/10.1007/s11239-020-02134-3
  3. Hoepel W. et al. Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses. bioRxiv July 13, 2020.  DOI: https://doi.org/10.1101/2020.07.13.190140
  4. Sung P-S and Hsieh S-L (2019) CLEC2 and CLEC5A: Pathogenic Host Factors in Acute Viral Infections. Front. Immunol. 10:2867. DOI:https://doi.org/10.3389/fimmu.2019.02867
  5. Behnen M. Immobilized Immune Complexes Induce Neutrophil Extracellular Trap Release by Human Neutrophil Granulocytes via Fcγ RIIIB and Mac-1. The Journal of Immunology July 2014. DOI: https://doi.org/10.4049/jimmunol.1400478
  6. Strich, J. et al. Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic. Journal of Infectious Disease December 24, 2020. DOI: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaa789/6046406