SOUTH SAN FRANCISCO, Calif.,
March 11, 2021 /PRNewswire/
-- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced
the completion of patient enrollment in a multi-center Phase 2
clinical trial to evaluate the safety of fostamatinib, Rigel's 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 is marketed in the U.S. as
TAVALISSE® (fostamatinib disodium hexahydrate) tablets,
and is approved in the U.S., Europe, and Canada as a treatment for adult chronic immune
thrombocytopenia (ITP).
The Phase 2 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.
This is a double-blind, placebo-controlled Phase 2 clinical
trial that randomly assigned fostamatinib plus standard of
care (SOC) or matched placebo plus SOC (1:1) to 58 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 endpoint of this study is cumulative incidence of serious
adverse events (SAE) through day 29, with multiple secondary
endpoints designed to assess the early efficacy and clinically
relevant endpoints of disease course as well as in vitro
biological correlatives evaluating the effects of the drug on
pathways involved in the pathophysiology of COVID-19, including
NETosis. The NHLBI and Rigel expect to report topline data
from this clinical trial in April
2021.
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 TAVALISSE
Indication
TAVALISSE® (fostamatinib disodium hexahydrate) tablets
is indicated for the treatment of thrombocytopenia in adult
patients with chronic immune thrombocytopenia (ITP) who have had an
insufficient response to a previous treatment.
Important Safety Information
Warnings and
Precautions
- Hypertension can occur with TAVALISSE treatment. Patients with
pre-existing hypertension may be more susceptible to the
hypertensive effects. Monitor blood pressure every 2 weeks until
stable, then monthly, and adjust or initiate antihypertensive
therapy for blood pressure control maintenance during therapy. If
increased blood pressure persists, TAVALISSE interruption,
reduction, or discontinuation may be required.
- Elevated liver function tests (LFTs), mainly ALT and AST, can
occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT
or AST increase to >3 x upper limit of normal, manage
hepatotoxicity using TAVALISSE interruption, reduction, or
discontinuation.
- Diarrhea occurred in 31% of patients and severe diarrhea
occurred in 1% of patients treated with TAVALISSE. Monitor patients
for the development of diarrhea and manage using supportive care
measures early after the onset of symptoms. If diarrhea becomes
severe (≥Grade 3), interrupt, reduce dose or discontinue
TAVALISSE.
- Neutropenia occurred in 6% of patients treated with TAVALISSE;
febrile neutropenia occurred in 1% of patients. Monitor the ANC
monthly and for infection during treatment. Manage toxicity with
TAVALISSE interruption, reduction, or discontinuation.
- TAVALISSE can cause fetal harm when administered to pregnant
women. Advise pregnant women the potential risk to a fetus. Advise
females of reproductive potential to use effective contraception
during treatment and for at least 1 month after the last dose.
Verify pregnancy status prior to initiating TAVALISSE. It is
unknown if TAVALISSE or its metabolite is present in human milk.
Because of the potential for serious adverse reactions in a
breastfed child, advise a lactating woman not to breastfeed during
TAVALISSE treatment and for at least 1 month after the last
dose.
Drug Interactions
- Concomitant use of TAVALISSE with strong CYP3A4 inhibitors
increases exposure to the major active metabolite of TAVALISSE
(R406), which may increase the risk of adverse reactions. Monitor
for toxicities that may require a reduction in TAVALISSE dose.
- It is not recommended to use TAVALISSE with strong CYP3A4
inducers, as concomitant use reduces exposure to R406.
- Concomitant use of TAVALISSE may increase concentrations of
some CYP3A4 substrate drugs and may require a dose reduction of the
CYP3A4 substrate drug.
- Concomitant use of TAVALISSE may increase concentrations of
BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp)
substrate drugs (eg, digoxin), which may require a dose reduction
of the BCRP and P-gp substrate drug.
Adverse Reactions
- Serious adverse drug reactions in the ITP double-blind studies
were febrile neutropenia, diarrhea, pneumonia, and hypertensive
crisis, which occurred in 1% of TAVALISSE patients. In addition,
severe adverse reactions occurred including dyspnea and
hypertension (both 2%), neutropenia, arthralgia, chest pain,
diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache,
syncope, and hypoxia (all 1%).
- Common adverse reactions (≥5% and more common than placebo)
from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea,
dizziness, ALT and AST increased, respiratory infection, rash,
abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSE.com for full Prescribing
Information.
To report side effects of prescription drugs to the FDA,
visit www.fda.gov/medwatch or call 1-800-FDA-1088
(800-332-1088).
TAVALISSE and TAVLESSE are registered trademarks of Rigel
Pharmaceuticals, Inc.
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.
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, Rigel's
expectations on timing to report topline data from the Phase 2
trial, and the potential clinical benefit of fostamatinib for the
treatment of hospitalized COVID-19 patients and the role of SYK
inhibition in potentially improving outcomes for 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," "could," "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, unforeseen and foreseen delays in
Rigel's ongoing clinical trials; risks that the FDA, EMA or other
regulatory authorities may make adverse decisions regarding
fostamatinib or any other of Rigel's products and product
candidates; risks that 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 misuse; 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 . In addition, the ongoing
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.
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.