-- Provides Update on ACTIV-4 Host Tissue
Trial --
SOUTH
SAN FRANCISCO, Calif., Oct. 11,
2023 /PRNewswire/ -- Rigel Pharmaceuticals,
Inc. (Nasdaq: RIGL) today announced an upcoming oral
presentation highlighting data from the FOCUS Phase 3 clinical
trial of fostamatinib in hospitalized COVID-19 patients without
respiratory failure who have certain high-risk prognostic
factors at IDWeek 2023 being held October 11-15, 2023, in Boston, MA and provided an update on the
ACTIV-4 Host Tissue trial of fostamatinib in hospitalized patients
with COVID-19.
"From the outset of the COVID-19 pandemic, we were hopeful of
making an impact. However, our focus remains on our
hematology-oncology commercial and clinical portfolio," said
Raul Rodriguez, Rigel's president
and CEO. "As we have previously reported, we do not plan to
submit an Emergency Use Authorization or a supplemental New Drug
Application given the end of the federal COVID-19 Public
Health Emergency in May 2023, and
based on feedback from the FDA, US Department of Defense and other
advisors regarding the program's regulatory requirements, costs,
timeline and potential for success."
Details of the oral presentation at IDWeek 2023 are as
follows:
Abstract #: 88
Title: Fostamatinib for the Treatment of Hospitalized
Patients With COVID-19 Who Required Oxygen Supplementation: Results
of a Phase 3 Trial
Presenter: Dr. Deepa Gotur,
MD, FCCP, FCCM, Associate Professor Clinical Medicine, Weill
Cornell Medical College and Houston Methodist Hospital,
Houston, TX
Session Name: Clinical Trials
Date: Thursday, October 12,
2023
Presentation Time: 11:15 – 11:30AM
ET
Location: 102 AB, Boston Convention and Exhibition
Center
- This presentation reports severe COVID-19 is linked to
hyperactivation of the host immune response involving signaling
through multiple spleen tyrosine kinase (SYK) pathways.
Fostamatinib is an orally administered potent and selective
inhibitor of SYK that has been approved in the US, Canada, Japan, and Europe for the treatment of chronic immune
thrombocytopenia (ITP).
- The FOCUS Phase 3 clinical trial was a double-blind,
randomized, placebo-controlled trial of fostamatinib in adults
hospitalized for COVID-19 who required oxygen supplementation
(NCT04629703). Patients were randomly assigned 1:1 to receive
fostamatinib (150 mg BID administered orally) or placebo for 14
days. All patients additionally received standard of care at their
hospital. The primary endpoint was days on oxygen (days 1-29).
- A total of 280 patients underwent randomization (with 141
assigned to fostamatinib and 139 to placebo). The primary endpoint
was met; those who received fostamatinib had lower mean days on
oxygen than those who received placebo (4.8 vs. 7.6 days,
p=0.0136).
- Fostamatinib showed significance or trend towards significance
in all secondary endpoints of reducing mortality and morbidity
compared to placebo. The mean change in the 8-point ordinal score
from baseline to the average of Day 5 to 15 was significantly
improved in patients who received fostamatinib vs. placebo
(p=0.0092). Furthermore, 6 patients were enrolled with
baseline ordinal score of 6 (3 in each group). All patients in the
fostamatinib group survived, and all in the placebo group died by
Day 30. A significantly higher proportion of patients who received
fostamatinib were discharged from the hospital by Day 15 compared
to placebo (p=0.0029). Significantly more patients were
alive and oxygen-free by Day 29 and Day 60 with fostamatinib
treatment in comparison to placebo (p=0.0213 and
p=0.0271, respectively). Treatment-emergent adverse events
were consistent with previous studies and were similar between the
2 groups.
- The addition of fostamatinib to standard of care treatment
resulted in significantly fewer days on oxygen, an improved 8-point
ordinal scale score, and significantly more patients alive and
oxygen-free by Day 60 compared to placebo in patients with COVID-19
requiring hospitalization and supplemental oxygen.
ACTIV-4 Host Tissue (NECTAR) Trial Update
On
September 26, 2023, the Data and
Safety Monitoring Board (DSMB) recommended that the fostamatinib
study arm of the ACTIV-4 Host Tissue (NECTAR) platform cease
enrollment. Based on their review of a conditional power analysis,
the DSMB determined that there was an extremely low likelihood of
fostamatinib providing benefits related to the primary outcome
(Oxygen Free Days) or other secondary outcomes in patients
hospitalized and on oxygen therapy for COVID-19. No safety
concerns were identified.
The National Heart, Lung, and Blood Institute (NHLBI), part of
the National Institutes of Health, concurs with the DSMB's
recommendations and has asked the trial investigators to cease
enrollment, complete follow-up for participants already enrolled,
and complete study closeout. The full study data will be analyzed
and disseminated as previously planned.
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. (Nasdaq: RIGL) is a biotechnology
company dedicated to discovering, developing and providing novel
therapies that significantly improve the lives of patients with
hematologic disorders and cancer. Founded in 1996, Rigel is based
in South San Francisco,
California. For more information on Rigel, the Company's
marketed products and pipeline of potential products, visit
www.rigel.com.
- 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
- 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
- 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
Forward-Looking Statements
This release contains
forward-looking statements relating to, among other things, our
expectations related to the role of fostamatinib in the treatment
of patients with COVID-19 and in future pandemics, including next
steps in collaboration with Rigel's partner, the U.S. Department of
Defense, and the timing and results of the ACTIV-4 study. 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. Forward-looking statements are neither historical facts
nor assurances of future performance. Instead, they are based on
Rigel's current beliefs, expectations, and assumptions regarding
the future of our business, future plans and strategies,
projections, anticipated events and trends, the economy and other
future conditions, and hence they inherently involve significant
risks, uncertainties and changes in circumstances that are
difficult to predict and many of which are outside of our control.
Therefore, you should not rely on any of these forward-looking
statements. 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 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, 2023, and subsequent
filings. Any forward-looking statement made by us in this press
release is based only on information currently available to us and
speaks only as of the date on which it is made. 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, except as required by law.
Investors & Media Contacts:
Investors:
Rigel Pharmaceuticals, Inc.
650.624.1232
ir@rigel.com
Media:
David Rosen
Argot Partners
Phone: 212.600.1902
Email: david.rosen@argotpartners.com
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SOURCE Rigel Pharmaceuticals, Inc.