SOUTH SAN FRANCISCO, Calif.,
April 13, 2021 /PRNewswire/ -- Rigel
Pharmaceuticals, Inc. (Nasdaq: RIGL), today announced positive
topline results from a multi-center, Phase 2 clinical trial to
evaluate the safety of fostamatinib, its oral spleen tyrosine
kinase (SYK) inhibitor, for the treatment of hospitalized
patients with COVID-19.
The trial, being conducted in collaboration with the National
Heart, Lung, and Blood Institute (NHLBI), part of the National
Institutes of Health (NIH), and Inova Health System, met its
primary endpoint of safety. Fostamatinib reduced the incidence
of Serious Adverse Events (SAEs) by half. By day 29, there
were three SAEs in the fostamatinib plus standard of care
(SOC) group of thirty patients compared to six SAEs in the placebo
plus SOC group of twenty-nine patients (p=0.23). Of these,
there was a reduction for the disease related SAE of hypoxia in the
fostamatinib group compared to placebo (1 vs 3, respectively;
p=0.29).
"Despite the growing arsenal of vaccines gaining emergency use
authorization, COVID-19 continues to spread and patients remain in
need of effective therapies. We are extremely pleased with the
outcome of this trial, which provides early indications of the
potential positive impact of fostamatinib for patients with
COVID-19," said Raul Rodriguez,
president and CEO of Rigel. "These results are an important
addition to the extensive accumulation of data evaluating
fostamatinib in COVID-19, which also include the ongoing Phase 2
study with Imperial College London and our own Phase 3 clinical
trial being conducted in the U.S. and Latin America."
"Fostamatinib was shown to be well tolerated in hospitalized
patients with COVID-19 on oxygen. Taken altogether, the results of
this trial suggest fostamatinib may be a useful addition to improve
the outcome of severe and critically ill COVID-19 patients who are
at the highest risk of death despite treatment with the best
conventional therapies under the current standard of care
(including remdesivir and steroids)," said Wolfgang Dummer, M.D., Ph.D., Rigel's Chief
Medical Officer. "Consistent with the observed clinical outcomes,
we are encouraged to see that in patients receiving fostamatinib
there was a more rapid decline in a number of inflammatory
biomarkers, that have previously been shown to be associated with
the course of COVID-19 disease, compared to those receiving
placebo."
Key findings from the Phase 2 clinical data readout include:
- At Day 29, in the overall population there were zero deaths
in the fostamatinib group of thirty patients compared to three
deaths in the placebo group of twenty-nine patients (p=0.07). In
more severe patients, those with an ordinal scale assessment of 6
or 7, the difference was zero of nineteen patients compared to
three of seventeen patients (p=0.049), respectively.
- There were four intubated patients in the trial on
mechanical ventilation (ordinal scale 7) with two patients
randomized to each treatment group. Both patients in the
fostamatinib group improved within 7 days and came off the
ventilator, while both patients in the placebo group
deceased.
- Fostamatinib was superior to placebo in
accelerating improvement in clinical status by day 15 (mean change
-3.6 compared to -2.6, p=0.035) and by day 29 (mean
change -4.2 compared to -3.3, p=0.12) using ordinal
scale assessments.
- The median number of days in the ICU was reduced by 4 days,
from 7 days in the placebo group to 3 days in the fostamatinib
group (p=0.07).
- Despite general SOC use of both steroids and remdesivir in
all 59 patients, there was a consistently greater reduction in
NETosis and other inflammatory biomarkers (CRP, Ferritin, D-Dimer,
Fibrinogen) in the fostamatinib group as compared to the placebo
group.
Investigators will conduct full and detailed analyses in the
coming weeks.
Based on these data, Rigel plans to discuss the potential for
emergency use authorization (EUA) with the U.S. Food and Drug
Administration (FDA) of fostamatinib as a treatment for
hospitalized patients with COVID-19. Fostamatinib, marketed
in the U.S. as TAVALISSE® (fostamatinib disodium
hexahydrate) tablets, is approved in the U.S., Europe, and Canada as a treatment for adult chronic immune
thrombocytopenia (ITP).
Phase 2 Clinical Trial Design
This is a double-blind,
placebo-controlled Phase 2 clinical trial sponsored by the
NHLBI, part of the NIH, in collaboration with Inova Health
System. Fifty-nine hospitalized patients with COVID-19 who were 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) were randomly
assigned to one of two cohorts: fostamatinib plus SOC or matched
placebo plus SOC (1:1). Treatment was administered orally
twice daily for 14 days, with a follow-up period through day 60.
Notably, all patients received dexamethasone as well as
remdesivir.
For more information on Rigel's comprehensive clinical program
in COVID-19, go to:
https://www.rigel.com/pipeline/proprietary-programs/covid-19
Conference Call and Webcast with Slides Today at 8:00 am Eastern Time
Rigel will hold a live conference call and webcast today to discuss
the Phase 2 trial results at 8:00 am Eastern
Time (5:00 am Pacific
Time).
Participants can access the live conference call by dialing
(877) 407-3088 (domestic) or (201) 389-0927 (international). The
conference call and accompanying slides will also be webcast live
and can be accessed from the Investor Relations section of the
company's website at www.rigel.com. The webcast will be archived
and available for replay after the call via the Rigel
website.
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 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 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 trial for
the treatment of warm autoimmune hemolytic anemia
(wAIHA)6; an NIH/NHLBI-sponsored Phase 2 trial for the
treatment of hospitalized COVID-196 patients, in
collaboration with Inova Health System; and a Phase 2 trial for the
treatment of COVID-19 being conducted by Imperial College London.
Additionally, Rigel has launched a Phase 3 clinical trial of
fostamatinib for the treatment of hospitalized COVID-19
patients.
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.
Please see www.TAVALISSE.com for 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. 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, the ability to improve the outcome of all COVID-19
patients by the use of fostamatinib; the continuing need for
effective therapies for COVID-19 patients; Rigel's plans for the
further investigation of fostamatinib in COVID-19 patients; as well
as Rigel's plans to seek emergency use authorization for
fostamatinib for the treatment of 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 that the FDA, EMA or other
regulatory authorities may make adverse decisions regarding
fostamatinib; risks that clinical trials may not be predictive of
real-world results or of results in subsequent clinical trials;
risks that fostamatinib 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 Annual
Report on Form 10-K for the year ended December 31, 2020 and subsequent filings. 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 Investor Contact:
Phone: 650.624.1232
Email: ir@rigel.com
Rigel Media Contact:
Phone: 508-314-3157
Email: emily.correia@syneoshealth.com
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SOURCE Rigel Pharmaceuticals, Inc.