Rigel Awarded $16.5 Million from DoD for Phase 3 Trial of Fostamatinib in COVID-19 Patients

Rigel Pharmaceuticals, Inc. announced on Jan. 29 it has been awarded $16.5 million by the U.S. Department of Defense’s (DOD) Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) to support Rigel’s ongoing Phase 3 clinical trial to evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients.

Fostamatinib is marketed in the U.S. as TAVALISSE^® (fostamatinib disodium hexahydrate) tablets, and is approved in the U.S., Europe, and Canada as a treatment for adult chronic immune thrombocytopenia (ITP).

“The DOD is pleased to support this effort, since repurposing an existing FDA-approved drug product for potential application as a COVID-19 treatment saves time and cost, enabling a much more rapid response to the pandemic,” said Dr. Jason Roos, from JPEO-CBRND. “This investment should speed up identification of safe and effective treatments for this formidable pandemic.”

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The Phase 3 clinical trial will evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients without respiratory failure that have certain high-risk prognostic factors. This multi-center, double-blind, placebo-controlled, adaptive design study is expected to enroll over 300 evaluable patients that will be randomly assigned to either fostamatinib plus standard of care (SOC) or matched placebo plus SOC (1:1). Treatment will be administered orally twice daily for 14 days. There will be a follow-up period to day 60. The primary endpoint of this study is the proportion of subjects who progress to severe/critical disease within 29 days.

The Other Transaction Authority (OTA) agreement was executed by JPEO-CBRND’s Joint Project Manager for Chemical, Biological, Radiological and Nuclear Medical (JPM CBRN Medical), in collaboration with the U.S. Army Contracting Command – Aberdeen Proving Ground, using Coronavirus Aid, Relief, and Economic Security (CARES) Act funding.

“Working alongside our industry partners to continue our fight against COVID-19 is crucial to the health and readiness of the Joint Force,” said Col. Ryan Eckmeier, who heads up JPM CBRN Medical. “These clinical trials may lead to the prevention of severe COVID-19 symptoms in our warfighters, bringing them more rapidly back to the fight.”

“We are grateful to receive this funding from the DOD and for their demonstrated commitment towards finding safe and effective treatments for COVID-19 patients,” said Raul Rodriguez, Rigel’s president and CEO. “These additional resources will contribute significantly to the advancement of our Phase 3 trial. Data from this trial, coupled with findings from the NIH-sponsored Phase 2 trial, which is anticipated to report topline results in April 2021, could potentially facilitate an EUA filing for a much needed therapy for hospitalized COVID-19 patients in the U.S.”

Fostamatinib is currently being studied in a Phase 3 trial for the treatment of warm autoimmune hemolytic anemia (wAIHA); an 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 being conducted by Imperial College London.

About COVID-19 and SYK Inhibition

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.^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.

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