SOUTH SAN FRANCISCO, Calif.,
Aug. 13, 2021 /PRNewswire/
-- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL), today announced
that the U.S. Food and Drug Administration (FDA) has informed the
Company that clinical data submitted in late-May from a 59-patient
NIH/NHLBI-sponsored Phase 2 trial of fostamatinib to treat
hospitalized patients suffering from COVID-19 are insufficient for
an emergency use authorization (EUA) at this time. The FDA noted in
their response that they remain committed to working with Rigel in
the development of fostamatinib for COVID-19 as the Company is
currently conducting a larger Phase 3 clinical trial evaluating
fostamatinib in hospitalized patients with COVID-19.
"With new virus variants spreading and vaccination rates
plateauing, there remains a need for therapies that can improve
outcomes for hospitalized patients, particularly patients suffering
from hyperinflammatory COVID-19-related complications," said
Raul Rodriguez, president and CEO of
Rigel. "The Rigel team continues to focus on enrolling our Phase 3
clinical trial, which we anticipate completing later this year, and
we look forward to providing further safety and efficacy data from
this larger, 308-patient trial of fostamatinib in COVID-19
patients. If this trial meets its endpoints, we plan to resubmit
our EUA application with this additional data."
Fostamatinib Clinical Development Program in
COVID-19
The broader clinical development program for
fostamatinib is comprised of three ongoing studies and a recently
completed Phase 2 study. These studies are evaluating a wide range
of hospitalized patients, including those not on oxygen therapy,
who are experiencing mild to severe COVID-19-related
complications:
- Rigel-led Phase 3 Trial. This ongoing 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 study will enroll ~308 evaluable
patients to either fostamatinib plus SOC or matched placebo
plus SOC (1:1). The primary endpoint of this study is the
proportion of patients who progress to severe/critical disease
within 29 days. The study has enrolled ~176 patients as of
August 12, 2021, and enrollment is
expected to be complete by year-end. More detail on the study can
be found on clinicaltrials.gov: NCT04629703.
- ACTIV-4 Host Tissue Phase 3 Trial. The Accelerating
COVID-19 Therapeutic Interventions and Vaccines (ACTIV) study,
initiated and funded by the National Heart Lung and Blood Institute
(NHLBI), part of the National Institutes of Health, 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. The study enrolled its first patient on
July 22, 2021. More detail on the
study can be found on clinicaltrials.gov: NCT04924660.
- Imperial College of London IST. The Imperial
College London Investigator-Sponsored Trial (IST) is a two-stage,
open-label, controlled clinical trial of patients randomized
(1:1:1) to fostamatinib, ruxolitinib, or SOC. The primary objective
will be to determine the efficacy of fostamatinib and the efficacy
of ruxolitinib compared to SOC to reduce the proportion of
hospitalized patients progressing from mild or moderate to severe
COVID-19 pneumonia. Rigel is providing support for this trial along
with Novartis. More detail on the study can be found on
clinicaltrials.gov: NCT04581954.
- NIH/NHLBI-sponsored Phase 2 Trial. This randomized,
double-blind, placebo-controlled study, which has been completed,
evaluated the safety of fostamatinib plus SOC and matched placebo
plus SOC (1:1) in hospitalized patients with COVID-19 requiring
supplemental oxygen. The primary endpoint was the cumulative
incidence of serious adverse events (SAEs) by Day 29. As previously
announced, the study met its primary endpoint of safety and
provided evidence of broad and consistent improvement in numerous
secondary endpoints including mortality, time to sustained
recovery, change in ordinal scale assessment, number of days on
oxygen, and number of days in the ICU. Results from this study have
been submitted for publication in a peer-reviewed medical journal.
More details on the study can be found on clinicaltrials.gov:
NCT04579393.
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
Spleen tyrosine kinase (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 thromboinflammation, alleviating organ dysfunction
in critically ill patients with COVID-19.
For more information on Rigel's comprehensive clinical program
in COVID-19, go to:
https://www.rigel.com/pipeline/proprietary-programs/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 for the
treatment of hospitalized high-risk patients with
COVID-197; an NIH/NHLBI-sponsored Phase 3 clinical trial
(ACTIV-4 Host Tissue Trial) for the treatment of COVID-19 in
hospitalized patients, and a Phase 2 clinical trial for the
treatment of COVID-19 being conducted by Imperial College
London.
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.
1. Berlin DA, Gulick RM, and Martinez FJ. Severe
Covid-19. N Engl J Med 2020. DOI:
https://doi.org/10.1056/NEJMcp2009575
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. 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
4. 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
5. 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
6. 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
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 COVID-19 clinical program, including
its use of fostamatinib to treat hospitalized patients suffering
from COVID-19; the clinical development program for fostamatinib,
including the Rigel-led Phase 3 Trial, the Accelerating COVID-19
Therapeutic Interventions and Vaccines (ACTIV) study and the
Imperial College of London Investigator-Sponsored Trial; and
Rigel's recently completed Phase 2 study on fostamatinib. 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 June 30, 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.