SOUTH
SAN FRANCISCO, Calif., Jan. 4, 2024
/PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq:
RIGL) today announced a collaboration with CONNECT, an
international collaborative network of pediatric cancer centers, to
conduct a Phase 2 clinical trial to evaluate
REZLIDHIA® (olutasidenib) in combination with
temozolomide as maintenance therapy in newly diagnosed pediatric
and young adult patients with high-grade glioma (HGG) harboring an
isocitrate dehydrogenase-1 (IDH1) mutation.
Under the collaboration, CONNECT will include olutasidenib in
CONNECT's TarGeT-D, a molecularly guided Phase 2 umbrella clinical
trial for HGG. The Rigel-sponsored arm will study
post-radiotherapy administration of olutasidenib in combination
with temozolomide followed by olutasidenib monotherapy as
maintenance treatment in newly diagnosed pediatric and young adult
patients (less than 39 years old) with IDH1 mutation positive HGG,
including diffuse intrinsic pontine glioma (DIPG), an aggressive
brain tumor with limited treatment options. Rigel will provide
funding up to $3 million and study
material over the four-year collaboration.
"We are excited to collaborate with CONNECT to evaluate
olutasidenib in high grade glioma," said Raul Rodriguez, Rigel's president and CEO. "We
believe olutasidenib has potential in a variety of cancers where
mIDH1 plays an important role and we look forward to
generating new data in this disease state, which has a high unmet
need. This collaboration builds on our hematology-oncology pipeline
expansion strategy and enables us to explore the potential of
olutasidenib in a focused and efficient manner."
This open label Phase 2 trial will be overseen by Drs.
Santosh Valvi and Nicholas Gottardo, Perth Children's Hospital,
Dr. Michael J Fisher, Children's Hospital of Philadelphia, and Dr. Maryam Fouladi, Nationwide Children's Hospital,
and aims to enroll approximately 60 patients. The primary objective
of the olutasidenib arm of the trial is to estimate
progression-free survival. The study will also characterize the
safety, tolerability, and pharmacokinetics of olutasidenib in
pediatric and young adult patients. The study is estimated to begin
enrolling patients in the first half of 2024 and will fulfill
Rigel's post-marketing pediatric study requirement related to the
FDA approval of REZLIDHIA in relapsed or refractory (R/R) AML.
In January 2023, data was
published in the peer-reviewed
journal Neuro-Oncology from a multicenter, open label,
Phase 1b/2 trial of 26 patients with
R/R and predominantly enhancing gliomas harboring an IDH1
mutation. The data showed that olutasidenib 150 mg BID was
well tolerated and demonstrated preliminary evidence of clinical
activity and prolonged disease control in this heavily pretreated
population. The authors noted that olutasidenib is a potent,
brain-penetrant, selective inhibitor of mutant IDH1.1
The paper, titled "Olutasidenib (FT-2102) in patients with relapsed
or refractory IDH1-mutant glioma: A multicenter, open-label, phase
Ib/II trial" can be accessed here.
REZLIDHIA is FDA-approved for the treatment of adult patients
with R/R acute myeloid leukemia (AML) with a susceptible IDH1
mutation as detected by an FDA-approved test.
About
REZLIDHIA®
INDICATION
REZLIDHIA is
indicated for the treatment of adult patients with relapsed or
refractory acute myeloid leukemia (AML) with a susceptible
isocitrate dehydrogenase-1 (IDH1) mutation as detected by an
FDA-approved test.
IMPORTANT SAFETY INFORMATION
WARNING:
DIFFERENTIATION SYNDROME Differentiation syndrome, which
can be fatal, can occur with REZLIDHIA treatment. Symptoms
may include dyspnea, pulmonary infiltrates/pleuropericardial
effusion, kidney injury, hypotension,
fever, and weight gain. If differentiation syndrome is
suspected, withhold REZLIDHIA and initiate
treatment with corticosteroids and hemodynamic monitoring until
symptom resolution.
|
WARNINGS AND PRECAUTIONS
Differentiation
Syndrome
REZLIDHIA can cause differentiation syndrome. In
the clinical trial of REZLIDHIA in patients with relapsed or
refractory AML, differentiation syndrome occurred in 16% of
patients, with grade 3 or 4 differentiation syndrome occurring in
8% of patients treated, and fatalities in 1% of patients.
Differentiation syndrome is associated with rapid proliferation and
differentiation of myeloid cells and may be life-threatening or
fatal. Symptoms of differentiation syndrome in patients treated
with REZLIDHIA included leukocytosis, dyspnea, pulmonary
infiltrates/pleuropericardial effusion, kidney injury, fever,
edema, pyrexia, and weight gain. Of the 25 patients who experienced
differentiation syndrome, 19 (76%) recovered after treatment or
after dose interruption of REZLIDHIA. Differentiation syndrome
occurred as early as 1 day and up to 18 months after REZLIDHIA
initiation and has been observed with or without concomitant
leukocytosis.
If differentiation syndrome is suspected, temporarily withhold
REZLIDHIA and initiate systemic corticosteroids (e.g.,
dexamethasone 10 mg IV every 12 hours) for a minimum of 3 days and
until resolution of signs and symptoms. If concomitant leukocytosis
is observed, initiate treatment with hydroxyurea, as clinically
indicated. Taper corticosteroids and hydroxyurea after resolution
of symptoms. Differentiation syndrome may recur with premature
discontinuation of corticosteroids and/or hydroxyurea treatment.
Institute supportive measures and hemodynamic monitoring until
improvement; withhold dose of REZLIDHIA and consider dose reduction
based on recurrence.
Hepatotoxicity
REZLIDHIA can cause hepatotoxicity,
presenting as increased alanine aminotransferase (ALT), increased
aspartate aminotransferase (AST), increased blood alkaline
phosphatase, and/or elevated bilirubin. Of 153 patients with
relapsed or refractory AML who received REZLIDHIA, hepatotoxicity
occurred in 23% of patients; 13% experienced grade 3 or 4
hepatotoxicity. One patient treated with REZLIDHIA in combination
with azacitidine in the clinical trial, a combination for which
REZLIDHIA is not indicated, died from complications of drug-induced
liver injury. The median time to onset of hepatotoxicity in
patients with relapsed or refractory AML treated with REZLIDHIA was
1.2 months (range: 1 day to 17.5 months) after REZLIDHIA
initiation, and the median time to resolution was 12 days (range: 1
day to 17 months). The most common hepatotoxicities were elevations
of ALT, AST, blood alkaline phosphatase, and blood bilirubin.
Monitor patients frequently for clinical symptoms of hepatic
dysfunction such as fatigue, anorexia, right upper abdominal
discomfort, dark urine, or jaundice. Obtain baseline liver function
tests prior to initiation of REZLIDHIA, at least once weekly for
the first two months, once every other week for the third month,
once in the fourth month, and once every other month for the
duration of therapy. If hepatic dysfunction occurs, withhold,
reduce, or permanently discontinue REZLIDHIA based on
recurrence/severity.
ADVERSE REACTIONS
The most common (≥20%) adverse
reactions, including laboratory abnormalities, were aspartate
aminotransferase increased, alanine aminotransferase increased,
potassium decreased, sodium decreased, alkaline phosphatase
increased, nausea, creatinine increased, fatigue/malaise,
arthralgia, constipation, lymphocytes increased, bilirubin
increased, leukocytosis, uric acid increased, dyspnea, pyrexia,
rash, lipase increased, mucositis, diarrhea and transaminitis.
DRUG INTERACTIONS
- Avoid concomitant use of REZLIDHIA with strong or moderate
CYP3A inducers.
- Avoid concomitant use of REZLIDHIA with sensitive CYP3A
substrates unless otherwise instructed in the substrates
prescribing information. If concomitant use is unavoidable, monitor
patients for loss of therapeutic effect of these drugs.
LACTATION
Advise women not to breastfeed during
treatment with REZLIDHIA and for 2 weeks after the last dose.
GERIATRIC USE
No overall differences in effectiveness
were observed between patients 65 years and older and younger
patients. Compared to patients younger than 65 years of age, an
increase in incidence of hepatotoxicity and hypertension was
observed in patients ≥65 years of age.
HEPATIC IMPAIRMENT
In patients with mild or moderate
hepatic impairment, closely monitor for increased probability of
differentiation syndrome.
Click here for Full Prescribing Information,
including Boxed WARNING.
To report side effects of prescription drugs to the FDA, visit
www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).
REZLIDHIA is a registered trademark of Rigel Pharmaceuticals,
Inc.
About Rigel
Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) is a biotechnology
company dedicated to discovering, developing and providing novel
therapies that significantly improve the lives of patients with
hematologic disorders and cancer. Founded in 1996, Rigel is based
in South San Francisco,
California. For more information on Rigel, the Company's
marketed products and pipeline of potential products,
visit www.rigel.com.
About CONNECT
CONNECT is an international collaborative network of pediatric
cancer centers with the objective to improve outcomes for children
with brain tumors. CONNECT conducts small, scientifically rational,
pilot and early phase studies to assess feasibility and early
efficacy of incorporating promising new therapies into established
frontline therapeutic regimens. For more information on CONNECT,
visit connectconsortium.org.
- de la Fuente M, et al. Olutasidenib (FT-2102) in patients
with relapsed or refractory IDH1-mutant glioma: A multicenter,
open-label, phase Ib/II trial. Neuro Oncol. 2023
Jan 5;25(1):146-156. doi:
10.1093/neuonc/noac139.
Forward Looking Statements
This press release contains forward-looking statements relating
to, among other things, that olutasidenib may provide a meaningful
approach to the treatment of patients with glioma, the enrollment
of patients in the Phase 2 study of olutasidenib, and the use of
the safety and efficacy data from the Phase 2 study of olutasidenib
in glioma. Any statements contained in this press release that are
not statements of historical fact may be deemed to be
forward-looking statements. Forward-looking statements can be
identified by words such as "aims", "expected", "explore"
"potential", "look forward", "believe", "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 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 FDA, European Medicines
Agency, PMDA or other regulatory authorities may make adverse
decisions regarding olutasidenib; risks that clinical trials
may not be predictive of real-world results or of results in
subsequent clinical trials; risks that olutasidenib 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,
2023 and subsequent filings. 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.
Investors & Media
Contacts:
Investors:
Rigel Pharmaceuticals,
Inc.
650.624.1232
ir@rigel.com
Media:
David
Rosen
Argot Partners
Phone: 212.600.1902
Email: david.rosen@argotpartners.com
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SOURCE Rigel Pharmaceuticals, Inc.