SOUTH SAN FRANCISCO, Calif.,
Sept. 17, 2020 /PRNewswire/ -- Rigel
Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced the start of a
multicenter, Phase 2 trial to evaluate the safety of fostamatinib,
its 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).
"With the ongoing pandemic continuing to cause tens of thousands
of new daily cases of COVID-19 across the U.S., there is a critical
need to not only stop the spread of the virus, but to also develop
new and effective therapies to treat the infected population,
including those with severe and life-threatening disease," said
Richard Childs, M.D., clinical
director of the NHLBI. "As we work with the broader community to
identify safe and effective therapeutic options for COVID-19
patients, we are hopeful that the investigation of fostamatinib
will potentially aid in the fight against this pandemic."
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.
"Working with Dr. Childs and his team at the NIH provides an
excellent platform to further explore the potential of fostamatinib
to treat and prevent conditions caused by an overactive immune
system in COVID-19 patients," said Raul
Rodriguez, Rigel's president and CEO. "COVID-19 infection
can lead to dangerous and potentially life-threatening immune
responses that can attack not only the lungs, but potentially other
organs. Based on our understanding of SYK's role in the
pathogenesis of the virus and fostamatinib's mechanism of action,
we believe expanding our clinical effort into this second
trial in COVID-19 related lung injuries is critical."
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 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.
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.
Recently, researchers at The Broad Institute of the Massachusetts Institute of Technology (MIT) and Harvard led a
screen focused on drug repurposing to identify U.S. Food and Drug
Administration (FDA) approved compounds that reduce mucin-1 (MUC1)
protein abundance. MUC1 is a biomarker used to predict the
development of acute lung injury and ARDS, and it correlates with
poor clinical outcomes. Of the 3,713 compounds that were screened,
fostamatinib was the only compound identified that both decreased
expression of MUC1 and is FDA approved.6 Additionally, a
recent study led by the Amsterdam University Medical Center at the
University of Amsterdam, found
that anti-Spike IgG from serum of severely ill COVID-19 patients
induces a hyperinflammatory response by human macrophages, a
response that can be counteracted by SYK inhibition with
fostamatinib. This study also found that anti-Spike IgG can break
down pulmonary endothelial barriers and induce microvascular
thrombosis.3 Fostamatinib is currently in a Phase 2
trial being conducted by Imperial College London to evaluate
the efficacy of fostamatinib for the treatment of COVID-19
pneumonia.
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). Fostamatinib is also currently being studied in an
investigator-sponsored trial conducted by Imperial College London
for the treatment of COVID-19 pneumonia7.
Rigel's clinical programs include a Phase 3 study of
fostamatinib in warm autoimmune hemolytic anemia (AIHA); a
completed Phase 1 study of R8357, a proprietary molecule
from its interleukin receptor associated kinase (IRAK) inhibitor
program; and an ongoing Phase 1 study of R5527, 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.
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. Alimova M. et al. A High Content Screen for Mucin-1-Reducing
Compounds Identifies Fostamatinib as a Candidate for Rapid
Repurposing for Acute Lung Injury during the COVID-19 pandemic.
bioRxiv June 30, 2020. DOI:
https://doi.org/10.1101/2020.06.30.180380
7. 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.