SOUTH SAN FRANCISCO, Calif.,
Jan. 10, 2022 /PRNewswire/
-- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today provided a
business update including preliminary 2021 full-year total revenue,
the status of the Phase 3 study in COVID-19, and upcoming catalysts
in 2022.
"Despite the challenges the global pandemic continued to present
in 2021, our team responded with creative solutions to navigate the
evolving landscape and now look forward to several catalysts that
have the potential to be transformative for the company in 2022,"
said Raul Rodriguez, Rigel's
president and chief executive officer. "We've made strategic
investments designed to accelerate TAVALISSE ITP sales in the U.S.,
prepare for pivotal readouts in two Phase 3 studies that have the
potential to expand the market for fostamatinib into new
indications such as wAIHA and COVID-19, and advance our
clinical-stage IRAK1/4 and RIPK1 programs into Phase 2
development."
Commercial and Preliminary Financial Update
In the fourth quarter of 2021, a total of 1,814 bottles of
TAVALISSE® (fostamatinib disodium
hexahydrate) were sold in the U.S., of which 1,785 were
shipped directly to patients and clinics, representing the highest
daily bottles shipped to patients and clinics in a quarter since
launch. For the full year ended December 31,
2021, 6,787 bottles of TAVALISSE were shipped directly to
patients and clinics, representing an increase of 8% compared to
2020. While Rigel is still in the process of determining final
results for the fourth quarter of 2021, Rigel expects to report net
product sales of $17.6 million
compared to $17.7 million for the
same period of 2020.
Contract revenues for the quarter ended December 31, 2021, are expected to be
approximately $2.8 million,
consisting of $1.8 million in revenue
from collaborative partners and $1.0
million in government contract revenue from the U.S.
Department of Defense (DOD).
For the fourth quarter of 2021, Rigel expects to report total
revenue of approximately $20.4
million.
The company expects to report cash, cash equivalents, and
short-term investments as of December 31,
2021, of approximately $124.9
million compared to $57.3
million as of December 31,
2020.
The above information is preliminary, has not been audited, and
is subject to change upon the audit of the company's financial
statements for the year ended December 31,
2021.
Portfolio Update
Phase 3 Trial in wAIHA
Enrollment of Rigel's FORWARD
study, a Phase 3 pivotal trial of TAVALISSE in patients with wAIHA,
is complete. Rigel expects to report topline data from the 24-week
study in mid-2022 and proceed with regulatory filings if the data
is positive. If approved, TAVALISSE has the potential to be the
first-to-market therapy for patients with wAIHA in 2023.
COVID-19 Program
Rigel's Phase 3 clinical trial
evaluating fostamatinib in high-risk patients hospitalized with
COVID-19 has enrolled 231 of the targeted 308 patients to date. In
December, Rigel expanded the inclusion criteria to include patients
with more severe disease (NIAID Ordinal Scale 6) to more accurately
reflect the clinically predominant patient population hospitalized
with COVID-19 and help speed enrollment. In collaboration with the
United States Food and Drug Administration (FDA) and DOD, Rigel has
also updated the primary endpoint for the study from progression to
severe disease within 29 days, to the number of days on
oxygen through day 29.
"As a study endpoint, reducing the number of days a patient
spends on supplemental oxygen has proven to be clinically
meaningful, is a good measure for recovery, and has been widely
used in other large NIH sponsored trials in the recent
past," said Wolfgang Dummer,
M.D., Ph.D., Rigel's chief medical officer. "The findings of the
NIH/NHLBI phase 2 study provided evidence of broad, consistent and
clinically meaningful improvement in mortality, time to sustained
recovery, and the number of days on oxygen, for patients treated
with fostamatinib in addition to standard of care. We look forward
to confirming these findings in a larger patient population in our
Phase 3 study."
This endpoint allows for closer comparison of the results with
earlier results from the NIH/NHLBI Phase 2 trial with fostamatinib
and various other NIH-sponsored trials, such as ACTIV-4, which uses
a similar outcome measure as a primary endpoint. Rigel expects
to complete enrollment and report topline data in mid-2022.
In addition to Rigel's Phase 3 study, fostamatinib is also being
evaluated as a treatment for COVID-19 in two ongoing
studies, the NIH/NHLBI-funded Phase 3 ACTIV-4 Host Tissue
trial and a Phase 2 open-label clinical trial conducted by Imperial
College London.
IRAK1/4 Program
Rigel expects to advance
R2899, a potent and selective IRAK1/4 inhibitor, into an
open-label Phase 1b/2 clinical study
in patients with low-risk myeloid dysplastic syndrome (MDS) in Q1
2022. R289 blocks inflammatory cytokine production in response to
toll-like receptor (TLR) and interleukin-1 receptor family (IL-1R)
signaling. TLRs and IL-1Rs play a critical role in the innate
immune response, and dysregulation of these pathways can lead to
various inflammatory conditions. Chronic stimulation of both these
receptor systems is thought to cause the pro-inflammatory
environment in the bone marrow responsible for persistent
cytopenias in lower-risk MDS patients1.
RIPK1 Program Partnered with Eli
Lilly
R5529, a potent and selective RIPK1
inhibitor, will advance into Phase 2 development in psoriasis in
the 1H 2022 with partner Lilly. RIPK1 is implicated in a broad
range of key inflammatory cellular processes and plays a key role
in TNF signaling, especially in the induction of pro-inflammatory
necroptosis. The program also includes RIPK1 compounds that cross
the blood-brain barrier (CNS-penetrants) to address
neurodegenerative diseases such as Alzheimer's disease and ALS.
Rigel is completing early discovery work on a potential candidate
that Lilly may advance into clinical development.
Progress on Global Expansion in ITP
In December 2021, partner Kissei reported positive
topline results for a Phase 3 study in ITP in Japan and is preparing a new drug application
(NDA) for submission to Japan's
Pharmaceuticals and Medical Devices Agency (PMDA). In October 2018, Rigel entered into an exclusive
license and supply agreement with Kissei to develop and
commercialize fostamatinib in all current and potential indications
in Japan, China, Taiwan
and the Republic of Korea. Fostamatinib has Orphan Drug Designation
in Japan and Korea.
About ITP
In patients with ITP, 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 are 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. Current therapies for ITP include steroids, blood
platelet production boosters (TPO receptor agonists) and
splenectomy. However, not all patients are adequately treated with
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 destroy 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. To date, there are no
disease-targeted therapies approved for AIHA, despite the unmet
medical need that exists for these patients. Warm antibody 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.
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 pro-inflammatory cytokine release by monocytes
and macrophages, production of neutrophil extracellular traps
(NETs) by neutrophils, and platelet aggregation.4,5,6,7
Furthermore, SYK inhibition in neutrophils and platelets may lead
to decreased thrombo-inflammation, 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 about 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
Rigel Pharmaceuticals, Inc., is a
biotechnology company dedicated to developing, and commercializing
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), the
United Kingdom, 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)8; a Phase 3 clinical trial (NCT04629703)
for the treatment of hospitalized high-risk patients with
mild-to-moderate COVID-198; an NIH/NHLBI-funded Phase 3
ACTIV-4 Host Tissue Study (NCT04924660) for the treatment of
COVID-19 in hospitalized patients on oxygen therapy, and a Phase 2
clinical trial (NCT04581954) 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 (RIPK1)
inhibitor program in clinical development with partner Eli Lilly
and Company. In addition, Rigel has product candidates in
development with partners BerGenBio ASA, and Daiichi Sankyo.
For further information, visit www.rigel.com or follow us on
Twitter or LinkedIn.
- Sallman, DA et al. Unraveling the Pathogenesis of MDS:
The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype.
Front Oncol. June 16, 2016.
DOI: https://doi.org/10.3389/fonc.2016.00151
- 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
- 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
- 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
- The product for this use or indication is investigational
and has not been proven safe or effective by any regulatory
authority.
- R289 and R552 are investigational compounds not approved by
FDA.
Forward Looking Statements
This press release
contains forward-looking statements relating to, among other
things, expected commercial and financial results for the fourth
quarter and fiscal year ended December 31,
2021, reporting of topline data from its Phase 3 trial in
wAIHA, its Phase 3 clinical trial evaluating fostamatinib on
COVID-19, its Phase 2 development in psoriasis of R552 with partner
Eli Lilly, and its partner Kissei's Phase 3 study in ITP-.
Forward-looking statements can be identified by words such as
"plan", "potential", "may", "expects", "will" and similar
expressions in reference to future periods. 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 and
uncertainties associated with the commercialization and marketing
of TAVALISSE; risks that the FDA, EMA, PMDA or other regulatory
authorities may make adverse decisions regarding fostamatinib;
risks that fostamatinib 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 Quarterly Report on Form 10-Q
for the quarter ended September 30,
2021. 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,
whether written or oral, that may be made from time to time,
whether as a result of new information, future developments or
otherwise, 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.
Contact:
For Investors &
Media
Jodi Sievers – Rigel
Pharmaceuticals
Phone: 650.624.1232
Email: ir@rigel.com
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SOURCE Rigel Pharmaceuticals, Inc.