SOUTH SAN FRANCISCO, Calif.,
Nov. 17, 2020 /PRNewswire/
-- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today announced
that it has reached agreement with the U.S. Food and Drug
Administration (FDA) on the final design of its FORWARD study, a
pivotal Phase 3 clinical trial of fostamatinib disodium hexahydrate
(fostamatinib) in warm autoimmune hemolytic anemia (AIHA). The
FDA agreed to Rigel's proposed durable response measure for the
primary efficacy endpoint as well as the inclusion of additional
secondary endpoints.
The Phase 3 clinical trial is a randomized, double-blind,
placebo-controlled study of approximately 90 patients with primary
or secondary warm AIHA who have failed at least one prior
treatment. The primary efficacy endpoint for the trial is a durable
response defined as a hemoglobin level ≥ 10 g/dl with an increase
from baseline of ≥ 2 g/dl on three consecutive available visits
during the 24-week treatment period, with the response not being
attributed to rescue therapy. This endpoint allows for missed
visits due to the COVID-19 pandemic without impacting a durable
outcome. As of November 5, the trial
had enrolled 57 of the 90 patients targeted for enrollment and
currently has over 90 clinical trial sites established across 22
countries.
"Our conversations with the FDA have enabled us to finalize the
primary efficacy endpoint for the only ongoing Phase 3 trial in
warm AIHA, a condition for which there is no approved therapy,"
said Raul Rodriguez, Rigel's
president and CEO. "We are over 60% of our enrollment target
despite the headwinds drug development is facing due to COVID-19.
We believe this progress is a result of the geographic diversity of
our clinical sites, the ability of fostamatinib to be given orally,
and the FDA's clinical trial guidance during the pandemic."
Fostamatinib is commercially available in the U.S. under the
brand name TAVALISSE® (fostamatinib disodium
hexahydrate) tablets, which is the first and only spleen tyrosine
kinase (SYK) inhibitor indicated for the treatment of
thrombocytopenia in adult patients with chronic ITP who have had an
insufficient response to a previous treatment. The FDA has granted
TAVALISSE Orphan Drug designation for the treatment of patients
with warm AIHA.
About AIHA
Autoimmune hemolytic anemia (AIHA) is a rare, serious blood
disorder in which the immune system produces antibodies that result
in 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 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 immune and
hematologic disorders, cancer and rare 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 has been approved by the European Commission for the
treatment of chronic immune thrombocytopenia in adult patients who
are refractory to other treatments and is marketed in Europe under the name TAVLESSE®
(fostamatinib).
Fostamatinib1 is currently being studied in a
Phase 3 trial for the treatment of warm autoimmune hemolytic anemia
(AIHA); a 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, we plan to
launch a Phase 3 clinical trial of fostamatinib for the treatment
of hospitalized COVID-19 patients in the fourth quarter of
2020.
Rigel's other clinical programs include an ongoing Phase 1 study
of R8351, a proprietary molecule from its interleukin
receptor associated kinase (IRAK) inhibitor program, and an ongoing
Phase 1 study of R5521, a proprietary molecule from its
receptor-interacting protein kinase (RIP) inhibitor program. In
addition, Rigel has product candidates in clinical development with
partners AstraZeneca, BerGenBio ASA, and Daiichi Sankyo.
1The 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 ability to complete enrollment in its
phase 3 clinical trial as a treatment for AIHA and the trial design
for such indication. 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,"
"aim," "believe," "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 fostamatinib in the U.S. and Europe; risks that the FDA, European Medicines
Agency (EMA) or other regulatory authorities may make adverse
decisions regarding fostamatinib or any of Rigel's product
candidates; risks that clinical trials may not be predictive of
real-world results or of results in subsequent clinical trials; the
availability of resources to develop and, if approved,
commercialize fostamatinib or any other of Rigel's product
candidates; the progress of our and our collaborators' product
development programs, including clinical testing, and the timing of
results thereof; our expectations with respect to regulatory
submissions and approvals; our research and development expenses;
protection of our intellectual property; 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, 2020. In addition, the
ongoing COVID-19 pandemic may result in further delays in Rigel's
studies and trials, or impact Rigel's sales and ability to obtain
supply of fostamatinib. 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 IR Contact: David Burke
Phone: 650.624.1232
Email: dburke@rigel.com
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SOURCE Rigel Pharmaceuticals, Inc.