SOUTH SAN FRANCISCO, Calif.,
Jan. 11, 2021 /PRNewswire/ -- Rigel Pharmaceuticals,
Inc. (Nasdaq: RIGL) today provided a business update,
including preliminary total revenue, TAVALISSE®
(fostamatinib disodium hexahydrate) bottles sold for the quarter,
Fast Track designation granted for warm autoimmune hemolytic anemia
(wAIHA), and the company's expanding COVID-19 program. The
company's president and CEO, Raul
Rodriguez, will provide a more detailed company overview
during his presentation taking place on Thursday, January 14, 2020 at 10:00 am ET at
the 39th Annual J.P. Morgan Virtual Healthcare Conference.
"Rigel's accomplishments during the extraordinary global events
of 2020 position the company well as we enter the new year," said
Raul Rodriguez, Rigel's president and CEO. "Annual sales of
TAVALISSE grew by 41% compared to 2019, and its use as an
earlier line treatment option for ITP is resonating with both
patients and physicians. We are continuing to enroll our Phase 3
trial in wAIHA and we have received Fast Track
designation from the FDA which is intended to expedite the review
of a potential regulatory filing.
"The availability of vaccines is a critical step in managing the
COVID-19 pandemic, but we expect there will continue to be a
significant need for therapeutics. Our Phase 3 trial in COVID-19
has launched and topline data from the National Institutes of
Health Phase 2 trial is expected in April, which will
provide a near-term look at the potential of fostamatinib in this
disease."
Commercial and Preliminary Financial Update
In
the fourth quarter of 2020, a total of 1,899 bottles of TAVALISSE
were sold in the U.S., of which 1,725 were shipped directly to
patients and clinics. While Rigel is still in the process of
determining final results for the fourth quarter of 2020, the
company expects to report net product sales of approximately
$17.7 million, compared to
$13.8 million in the same period of
2019, an increase of 28%.
Contract revenues from collaborations for the quarter ended
December 31, 2020, are expected to be
approximately $697,000, which
consists of $500,000 from Grifols
related to an option for commercialization in additional
territories and $197,000 in revenues
earned from the performance of certain research and development
services from Rigel's collaboration agreement with Grifols.
For the fourth quarter 2020, Rigel expects to report total
revenue of approximately $18.4 million.
The company expects to report cash, cash equivalents and
short-term investments as of December 31,
2020 of approximately $57.3 million, compared to $98.0 million as of December 31, 2019.
The above information is preliminary, has not been audited and
is subject to change upon completion of the audit of the company's
financial statements as of and for the year ended December 31, 2020.
Portfolio Update
Phase 3 Trial in wAIHA
The
U.S. Food and Drug Administration (FDA) has granted Fast Track
designation to TAVALISSE for the treatment of wAIHA based on the
significant medical need that exists and the product's potential in
the treatment of these patients. Fast Track designation is designed
to enable an expedited review process for any potential regulatory
filings. Currently, the study has enrolled 64 of 90, or 71%, of the
patients planned for enrollment.
COVID-19 Program
The Phase 2 clinical trial sponsored
by NIH/NHLBI, in collaboration with Inova Health System, to
evaluate the safety of fostamatinib for the treatment of COVID-19
has enrolled 44 of the 60 patients planned for enrollment. In this
trial, patients are being randomized to fostamatinib plus standard
of care (SOC) or matched placebo plus SOC (1:1), 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. Rigel anticipates topline data to be reported in
April of this year.
In addition, Rigel has launched its Phase 3 clinical trial to
evaluate the safety and efficacy of fostamatinib in hospitalized
COVID-19 patients without respiratory failure that have certain
high-risk prognostic factors. The multi-center, double-blind,
placebo-controlled, adaptive design study is expected to enroll
over 300 evaluable patients that will be randomly assigned to
either fostamatinib plus SOC or matched placebo plus SOC (1:1).
Treatment will be administered orally twice daily for 14 days with
a follow-up period to day 60. The primary endpoint of this study is
the proportion of subjects who progress to severe/critical disease
within 29 days.
In December, the Journal of Infectious Diseases (JID) published
research from NIH which demonstrated that R406, the active
metabolite of fostamatinib, was able to inhibit NETosis ex vivo in
donor plasma from patients with COVID-19. NETosis is a unique type
of cell death resulting in the release of neutrophil extracellular
traps (NETs). NETs contribute to thromboinflammation and have been
associated with mortality in COVID-19. These data provide insights
for how fostamatinib may mitigate neutrophil-associated mechanisms
contributing to COVID-19 immunopathogenesis.1
Clinical Development Pipeline
Rigel's IRAK1/4 program
includes R835, an orally available, potent and selective inhibitor
and the only molecule in clinical development that inhibits both
IRAK1 and IRAK4. The company plans to pursue this program's
potential in hematology/oncology and rare diseases, where it
believes there are areas of significant unmet medical
need.
Rigel has an extensive RIPK1 inhibitor program. This
program includes R552, an oral systemic RIPK1 inhibitor which has
completed a Phase 1 study, as well as RIPK1 inhibitor candidates
that cross the blood-brain barrier (CNS-penetrants). RIPK1
inhibitors have broad potential in numerous large indications. In
order to fully develop these assets, Rigel intends to enter into a
collaboration for this program.
39th Annual J.P. Morgan Webcast Presentation
Details
Rigel's presentation will be webcast and is
scheduled to take place Thursday, January
14 at 10:00 am ET. To access
the live and subsequently archived webcast, go to the Investor
Relations section of the company's website at www.rigel.com. Please
connect to the website several minutes prior to the start of the
live webcast to ensure adequate time for any software download that
may be necessary.
About ITP
In patients with ITP (immune
thrombocytopenia), the immune system attacks and destroys the
body's own blood platelets, which play an active role in blood
clotting and healing. Common symptoms of ITP include fatigue,
excessive bruising, and bleeding. People suffering with chronic ITP
may live with an increased risk of severe bleeding events that can
result in serious medical complications or even death. In addition
to fostamatinib, current therapies for ITP include steroids, blood
platelet production boosters (TPO-RAs) and splenectomy. However,
not all patients respond to existing therapies. As a result, there
remains a significant medical need for additional treatment options
for patients with ITP.
About AIHA
Autoimmune hemolytic anemia (AIHA) is a
rare, serious blood disorder in which the immune system produces
antibodies that recognize and mediate the destruction of the body's
own red blood cells. AIHA affects approximately 45,000 adult
patients in the U.S. and can be a severe, debilitating disease.
Warm AIHA (wAIHA), the most common form of AIHA, is characterized
by the presence of antibodies that react with the red blood cell
surface at body temperature. To date, there are no disease-targeted
therapies approved for AIHA, despite the unmet medical need that
exists for these patients.
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.2 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.3
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.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.
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.
Fostamatinib7 is currently being studied in a Phase 3
trial for the treatment of warm autoimmune hemolytic anemia
(wAIHA); an NIH/NHLBI-sponsored Phase 2 trial for the treatment of
hospitalized COVID-19 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 launched
a Phase 3 clinical trial of fostamatinib for the treatment of
hospitalized COVID-19 patients.
Rigel's other clinical programs include an ongoing Phase 1 study
of R8357, a proprietary molecule from its interleukin
receptor-associated kinase (IRAK) inhibitor program, and a recently
completed Phase 1 study of R5527, a proprietary molecule
from its receptor-interacting serine/threonine-protein kinase
(RIPK) inhibitor program. In addition, Rigel has product candidates
in clinical development with partners AstraZeneca, BerGenBio ASA,
and Daiichi Sankyo.
1. Strich, J. et al. Fostamatinib Inhibits Neutrophils
Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential
Therapeutic. Journal of Infectious Disease December 24, 2020
https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiaa789/6046406
2. Berlin DA, Gulick RM, Martinez FJ. Severe Covid-19. N Engl J Med
2020
3. 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
4. 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
5. 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
6. 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
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, the
commercial success of TAVALISSE in the U.S.; Rigel's ability to
achieve development and commercial milestones; Rigel's expected
operating results for the quarter ending and as of December 31, 2020, including net sales and cash,
cash equivalents and short-term investments; expectations related
to the market opportunity for fostamatinib as a COVID-19
therapeutic; Rigel's ability to enter into a collaboration
for its RIPK1 inhibitor program; and the safety, tolerability,
design, timing and results of Rigel's products, product candidates
and clinical trials. 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,"
intends," "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 Rigel may not be able to enter into a
definitive agreement regarding its RIPK1 program on terms favorable
or acceptable to Rigel, or at all; 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 Annual Report on Form 10-K for the year
ended December 31, 2019 and Quarterly
Report on Form 10-Q for the quarter ended September 30, 2020. 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.
IR Contact: David Burke
Phone: 650.624.1232
Email: ir@rigel.com
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SOURCE Rigel Pharmaceuticals, Inc.