SOUTH SAN FRANCISCO, Calif.,
Oct. 9, 2020 /PRNewswire/ -- Rigel
Pharmaceuticals, Inc. (Nasdaq: RIGL) today 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 is sponsored by the National Heart, Lung,
and Blood Institute (NHLBI), part of the National Institutes
of Health (NIH), in collaboration with Inova® Health
System. Fostamatinib, marketed in the U.S. as TAVALISSE®
(fostamatinib disodium hexahydrate) tablets, is approved in the
U.S. and Europe as a treatment for
adult chronic immune thrombocytopenia (ITP).
"As mortality continues to rise, it is evident that new
therapeutics selectively targeting immune response are desperately
needed to treat patients infected with SARS-CoV-2," stated Dr.
Richard Childs, M.D., clinical
director of the NHLBI. "This is a rigorously-designed clinical
trial, which should provide insight into the potential safety and
efficacy of fostamatinib in the treatment of severely ill patients
suffering from COVID-19."
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.
"We are very excited to be a part of this clinical trial with
the NIH/NHLBI and Rigel. This study fits seamlessly within our
portfolio of research options that we have within the Inova Health
System to offer our COVID-19 population," said Dr. Steven Nathan M.D., medical director,
Advanced Lung Disease & Lung Transplant Program, at Inova.
"Research into novel compounds is a key component in finding
therapeutic options for COVID-19 patients, and with the first
patients enrolled, we are one step closer to understanding the
potential of fostamatinib and SYK inhibition in this disease."
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 (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.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.
About Rigel (www.rigel.com)
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 pioneering
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 (SYK) 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 (AIHA);
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 (IRAK) inhibitor program,
and an ongoing Phase 1 study of R5526, a proprietary
molecule from its receptor-interacting protein kinase (RIP)
inhibitor program. In addition, Rigel has product candidates in
clinical development with partners AstraZeneca, BerGenBio ASA, and
Daiichi Sankyo.
Please see www.TAVALISSE.com for the full Prescribing
Information.
- Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J
Med 2020
- 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
- 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
- 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
- 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
- The product for this use or indication is investigational
and has not been proven safe or effective by any regulatory
authority.
Forward Looking Statements
This release contains
forward-looking statements relating to, among other things, Rigel's
plans to support the NIH Phase 2 trial, the trial design, the
potential clinical benefit of fostamatinib for the treatment of
hospitalized COVID-19 patients and the role of SYK inhibition in
potentially improving outcomes of critically ill COVID-19 patients,
including by alleviating thromboinflammation. Any statements
contained in this press release that are not statements of
historical fact may be deemed to be forward-looking statements.
Words such as "potential," "may," "aim," "believe," "expects" and
similar expressions are intended to identify these forward-looking
statements. These forward-looking statements are based on Rigel's
current expectations and inherently involve significant risks and
uncertainties. Actual results and the timing of events could differ
materially from those anticipated in such forward looking
statements as a result of these risks and uncertainties, which
include, without limitation, risks and uncertainties associated
with the commercialization and marketing of fostamatinib in the
U.S. and Europe; risks that the
FDA, European Medicines Agency (EMA) or other regulatory
authorities may make adverse decisions regarding fostamatinib or
any of Rigel's product candidates; risks that clinical trials may
not be predictive of real-world results or of results in subsequent
clinical trials; the availability of resources to develop and, if
approved, commercialize fostamatinib or any other of Rigel's
product candidates; the progress of our and our collaborators'
product development programs, including clinical testing, and the
timing of results thereof; our expectations with respect to
regulatory submissions and approvals; our research and development
expenses; protection of our intellectual property, market
competition; as well as other risks detailed from time to time in
Rigel's reports filed with the Securities and Exchange Commission,
including its Quarterly Report on Form 10-Q for the quarter ended
June 30, 2020. In addition, the
ongoing COVID-19 pandemic may result in further delays in Rigel's
studies and trials, or impact Rigel's sales and ability to obtain
supply of fostamatinib. Rigel does not undertake any obligation to
update forward-looking statements and expressly disclaims any
obligation or undertaking to release publicly any updates or
revisions to any forward-looking statements contained
herein.
Rigel IR Contact: David Burke
Phone: 650.624.1232
Email: dburke@rigel.com
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SOURCE Rigel Pharmaceuticals, Inc.