SOUTH SAN FRANCISCO, Calif.,
June 29, 2021 /PRNewswire/ -- Rigel
Pharmaceuticals, Inc. (Nasdaq: RIGL), today announced that
fostamatinib, the Company's novel oral spleen tyrosine kinase (SYK)
inhibitor, has been selected for a National Institutes of Health
(NIH) ACTIV-4 (Accelerating COVID-19 Therapeutic Interventions and
Vaccines) trial in hospitalized patients with COVID-19.
The ACTIV-4 Host Tissue trial is a large, multi-site trial
funded by the National Heart, Lung, and Blood Institute (NHLBI) of
the NIH and coordinated by Vanderbilt
University Medical Center (VUMC). The trial is evaluating
treatments, including fostamatinib, that aim to protect and heal
host tissues in hospitalized patients with COVID-19.
This study follows a recently completed NHLBI/NIH-sponsored
Phase 2 study (NCT04579393), with positive topline
results, that evaluated fostamatinib in hospitalized adults
with COVID-19. The study met its primary endpoint of safety
and showed broad and consistent improvement in numerous efficacy
endpoints including mortality, ordinal scale assessment, and number
of days in the ICU. These data were submitted as part of a request
for an emergency use authorization (EUA) from the U.S. Food and
Drug Administration (FDA) for fostamatinib in hospitalized patients
diagnosed with COVID-19. These data have also been submitted for
publication in a peer-reviewed medical journal.
"Despite welcome advances in some areas, COVID-19 and its
variants will remain a real public health threat for the
foreseeable future, particularly for those with pre-existing
conditions," said Raul Rodriguez,
Rigel's president and CEO. "The teams at the NIH and VUMC are
ideally positioned to continue to advance clinical efforts for
COVID-19 related lung injuries, including the study of
fostamatinib's potential to treat and prevent conditions caused by
an overactive immune system in COVID-19 patients," he added.
"Fostamatinib will be the fourth arm of our ACTIV-4 Host Tissue
trial. The drugs tested on this platform offer an opportunity to
better understand both the central pathways of disease progression
and better ways to protect and heal the host tissues damaged by
COVID-19," said Dr. Sean P. Collins,
MD, MSc, ACTIV-4 Host Tissue Principal Investigator and Professor
of Emergency Medicine at VUMC.
ACTIV-4 Host Tissue Phase 3 Clinical Study
Design
The Collaborative Network of Networks for Evaluating
COVID-19 Therapeutic Strategies (CONNECTS) Master Protocol for
Clinical Trials Targeting Macro-, Micro-immuno-thrombosis, Vascular
Hyperinflammation, and Hypercoagulability and
Renin-angiotensin-aldosterone System (RAAS) in Hospitalized
Patients With COVID-19 (ACTIV-4 Host Tissue) is a multi-site,
randomized, placebo-controlled trial of therapies, including
fostamatinib, targeting the host response to COVID-19 in
hospitalized patients. The Master Protocol is designed to be
flexible in the number of study arms, the use of a single placebo
group, and the stopping and adding of new therapies. Each active
arm will include approximately 300 patients. Eligible participants
will include patients hospitalized for COVID-19 with laboratory
confirmed SARS-CoV-2 infection on oxygen therapy. The primary
outcome is oxygen free days through day 28. Secondary outcomes
include hospital mortality, use of mechanical ventilation, and WHO
scale scores. More detail on the study can be found on
clinicaltrials.gov: NCT04924660.
The study is part of Accelerating COVID-19 Therapeutic
Interventions and Vaccines (ACTIV), initiated and funded by the
NHLBI, part of the NIH. ACTIV is a public-private partnership that
unites partners from government, industry, academic and non-profit
organizations to prioritize and speed development of the most
promising COVID-19 treatments.
About COVID-19 & SYK Inhibition
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.3,4,5,6 Furthermore, SYK
inhibition in neutrophils and platelets may lead to
decreased thrombo-inflammation, alleviating organ dysfunction
in critically ill patients with COVID-19.
About Rigel
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 hematologic disorders, cancer and rare
immune 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 is also commercially available in
Europe (TAVLESSE) and Canada (TAVALISSE) for the treatment of
chronic immune thrombocytopenia in adult patients.
Fostamatinib is currently being studied in a Phase 3 clinical
trial (NCT03764618) for the treatment of warm autoimmune hemolytic
anemia (wAIHA)7; a Phase 3 clinical trial (NCT04629703)
for the treatment of hospitalized high-risk patients with
mild-to-moderate COVID-197; and a Phase 2 clinical trial
for the treatment of COVID-19 being conducted by Imperial College
London. An NIH/NHLBI-sponsored Phase 2 clinical trial for the
treatment of hospitalized patients with COVID-19, in collaboration
with Inova Health System, was recently completed.
Rigel's other clinical programs include its interleukin
receptor-associated kinase (IRAK) inhibitor program, and a
receptor-interacting serine/threonine-protein kinase (RIP1)
inhibitor program in clinical development with partner Eli Lilly
and Company. In addition, Rigel has product candidates in
development with partners AstraZeneca, BerGenBio ASA, and Daiichi
Sankyo.
For further information, visit www.rigel.com or follow us
on Twitter or LinkedIn.
Please see www.TAVALISSE.com for the full Prescribing
Information.
- Berlin DA, Gulick RM, and Martinez FJ. Severe Covid-19.
N Engl J Med 2020. DOI:
https://doi.org/10.1056/NEJMcp2009575
- 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. High titers and low fucosylation of early human
anti–SARS-CoV-2 IgG promote inflammation by alveolar
macrophages. Science Translational Medicine 02 Jun 2021.
DOI: https://www.doi.org/10.1126/scitranslmed.abf8654
- Sung P-S and Hsieh S-L. CLEC2 and CLEC5A: Pathogenic Host
Factors in Acute Viral Infections. Frontiers in Immunology
December 6, 2019. DOI:
https://doi.org/10.3389/fimmu.2019.02867 Strich J et al.
Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by
COVID-19 Patient Plasma: A Potential Therapeutic. Journal of
Infectious Disease March 15, 2021.
DOI: https://doi.org/10.1093/infdis/jiaa789
- Bye AP et al. Aberrant glycosylation of anti-SARS-CoV-2 IgG
is a pro-thrombotic stimulus for platelets. BioRxiv
March 26, 2021. DOI:
https://doi.org/10.1101/2021.03.26.437014
- 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
ability to further develop its clinical stage product candidates
and fostamatinib's potential to treat and prevent
conditions caused by COVID-19. 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", "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 TAVALISSE; risks that the FDA, EMA or other regulatory
authorities may make adverse decisions regarding fostamatinib;
risks that TAVALISSE clinical trials may not be predictive of
real-world results or of results in subsequent clinical trials;
risks that TAVALISSE may have unintended side effects, adverse
reactions or incidents of misuses; the availability of resources to
develop Rigel's product candidates; 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 March 31, 2021. In addition, the COVID-19
pandemic may result in further delays in Rigel's studies, trials
and sales, or impact Rigel's ability to obtain supply of TAVALISSE.
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.
Contact for Investors & Media:
Jodi Sievers - Rigel
Pharmaceuticals
Phone: 650.624.1232
Email: ir@rigel.com
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SOURCE Rigel Pharmaceuticals, Inc.