SOUTH
SAN FRANCISCO, Calif. and HOUSTON, Dec. 8, 2023
/PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) and
The University of Texas MD Anderson
Cancer Center (MD Anderson) today announced a multi-year strategic
development collaboration to expand the evaluation of
REZLIDHIA® (olutasidenib) in acute myeloid
leukemia (AML) and other hematologic cancers.
The alliance brings together MD Anderson's clinical research
expertise with Rigel's differentiated targeted molecule. Under the
strategic collaboration, Rigel and MD Anderson will evaluate the
potential of olutasidenib to treat newly diagnosed and relapsed or
refractory (R/R) patients with AML, higher-risk myelodysplastic
syndromes (MDS), and advanced myeloproliferative neoplasms (MPN),
in combination with other agents. The collaboration will also
support the evaluation of olutasidenib as monotherapy in lower-risk
MDS and as maintenance therapy in post-hematopoietic stem cell
transplant patients.
"We are excited to enter into this strategic alliance with the
exceptional team at MD Anderson to evaluate REZLIDHIA as a
potential therapy for a broad range of IDH1-mutant cancers," said
Raul Rodriguez, Rigel's president
and CEO. "We believe REZLIDHIA has the potential to become a
standard of care for patients in urgent need of new
hematology-oncology therapies. We look forward to a close
collaboration with MD Anderson to advance this as a new therapeutic
option for more patients."
REZLIDHIA is a potent, selective, oral, small-molecule inhibitor
of mutated IDH1 (mIDH1)1 designed to bind to and
inhibit mIDH1 to reduce 2-hydroxyglutarate levels and
restore normal cellular differentiation of myeloid
cells. REZLIDHIA is approved by the Food and Drug
Administration (FDA) for the treatment of adult patients with R/R
AML with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation
as detected by an FDA-approved test.
"Based on its differentiated profile and compelling clinical
data to date, REZLIDHIA has the potential, beyond its currently
approved indication, to benefit patients with various cancers where
mutant IDH1 is thought to play a role," said Courtney DiNardo, M.D., professor of Leukemia.
"We look forward to collaborating with Rigel to conduct in-depth
studies that will determine the broader potential of
REZLIDHIA in these patient populations."
Rigel and MD Anderson will jointly lead all clinical development
efforts, which will be overseen by a joint steering committee.
Rigel will provide $15 million in
time-based milestone payments and study material over the five-year
collaboration. Rigel will retain all rights to its programs under
the collaboration.
About AML
Acute myeloid leukemia (AML) is a rapidly progressing cancer of the
blood and bone marrow that affects myeloid cells, which normally
develop into various types of mature blood cells. AML occurs
primarily in adults and accounts for about 1 percent of all adult
cancers. The American Cancer Society estimates that in the United States alone, there will be about
20,380 new cases, most in adults, in 2023.2
Relapsed AML affects about half of all patients who, following
treatment and remission, experience a return of leukemia cells in
the bone marrow.3 Refractory AML, which affects between
10 and 40 percent of newly diagnosed patients, occurs when a
patient fails to achieve remission even after intensive
treatment.4 Quality of life declines for patients with
each successive line of treatment for AML, and well-tolerated
treatments in relapsed or refractory disease remain an unmet
need.
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 MD Anderson
The University of Texas MD Anderson
Cancer Center in Houston ranks as
one of the world's most respected centers focused on cancer patient
care, research, education and prevention. The institution's sole
mission is to end cancer for patients and their families around the
world, and, in 1971, it became one of the nation's first National
Cancer Institute (NCI)-designated comprehensive cancer centers.
MD Anderson is No. 1 for cancer in U.S. News & World
Report's "Best Hospitals" rankings and has been named one of the
nation's top two hospitals for cancer since the rankings began in
1990. MD Anderson receives a cancer center support grant from
the NCI of the National Institutes of Health (P30 CA016672).
- de Botton S, et al. Olutasidenib (FT-2102) induces durable
complete remissions in patients with relapsed or
refractory IDH1-mutated AML. Blood Advances.
February 1, 2023.
doi: https://doi.org/10.1182/bloodadvances.2022009411
- The American Cancer Society. Key Statistics for Acute Myeloid
Leukemia (AML). Revised January 12,
2023. Accessed Feb. 15, 2023:
https://www.cancer.org/cancer/acute-myeloid-leukemia/about/key-statistics.html
- Leukaemia Care. Relapse in Acute Myeloid Leukaemia (AML).
Version 3. Reviewed October 2021.
Accessed Feb 15, 2023:
https://media.leukaemiacare.org.uk/wp-content/uploads/Relapse-in-Acute-Myeloid-Leukaemia-AML-Web-Version.pdf
- Thol F, Schlenk RF, Heuser M, Ganser A. How I treat
refractory and early relapsed acute myeloid leukemia. Blood
(2015) 126 (3): 319-27. doi:
https://doi.org/10.1182/blood-2014-10-551911
Forward Looking Statements
This press release contains forward-looking statements relating
to, among other things, the potential and market opportunity of
REZLIDHIA (olutasidenib), both as a monotherapy and in combination
with other agents, as a therapeutic for R/R AML and other
conditions, the potential of REZLIDHIA as a therapy for a broad
range of mIDH1 cancers, the potential of REZLIDHIA to become a
standard of care for patients in need of new hematology-oncology
therapies and the benefits of Rigel's collaboration with MD
Anderson Cancer Center. 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 "potential", "may", "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 and uncertainties and are subject to 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, the risks and
uncertainties of clinical trials and drug development; risks and
uncertainties of commercialization and marketing of olutasidenib;
risks that 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 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
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.
Rigel Investor & 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
MD Anderson Media Contact:
Clayton Boldt, Ph.D.
Public Relations
Phone: 713.792.9518
Email: CRBoldt@MDAnderson.org
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SOURCE Rigel Pharmaceuticals, Inc.