- Durable remissions observed in patients relapsed or refractory
to prior venetoclax-based regimens
- Data featured in a poster presentation at the European
Hematology Association (EHA) 2023 Hybrid Congress
SOUTH
SAN FRANCISCO, Calif., June 7, 2023
/PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today
announced promising data from an analysis of the Phase 2 study
evaluating REZLIDHIA® (olutasidenib), a potent,
selective, oral, small-molecule inhibitor of mutant isocitrate
dehydrogenase-1 (mIDH1)1, in patients with
mIDH1 acute myeloid leukemia (AML) who were
relapsed/refractory (R/R) to prior venetoclax-based regimens. The
data are being presented in a poster at the EHA2023 Hybrid
Congress.
"We are encouraged by the strong efficacy and safety results
from olutasidenib in patients with mIDH1 R/R AML who had
previously been treated with venetoclax combination regimens, a
standard treatment for patients unfit for chemotherapy," said
Raul Rodriguez, Rigel's president
and CEO. "These data reinforce REZLIDHIA as a valuable treatment
option for these patients, a historically challenging population to
treat."
"The data from patients who were relapsed/refractory to prior
venetoclax combination-based regimens enrolled in the Phase 2 study
of REZLIDHIA (olutasidenib) in patients with mIDHl1 AML is
promising and appears clinically meaningful," said Jorge E. Cortes, M.D., Director, Georgia Cancer
Center, Cecil F. Whitaker Jr., GRA
Eminent Scholar Chair in Cancer, and Phase 2 trial investigator.
"With the trial's compelling data in duration of response and
favorable tolerability profile, REZLIDHIA is an important treatment
option for these patients, including those who have received prior
venetoclax."
The poster titled "Olutasidenib in Post-Venetoclax Patients with
Mutant IDH1 AML" examines a subset of 17 patients from the Phase 2
study of olutasidenib who had previously received venetoclax
combination regimens. Key points from the presentation are
summarized below:
- Olutasidenib induced durable remissions in patients with mIDH1
R/R AML, including those failing prior treatment with a
venetoclax-based regimen
- Of the 17 patients with prior venetoclax treatment, 5 were
ongoing and 12 discontinued treatment as of the analysis cutoff
date of June 18, 2021
- The best response to olutasidenib was CR/CRh in 5/17 (29.4%),
of which 4 (23.5%) were CR
- In the 8 patients who previously received the combination of
venetoclax and azacitadine, a standard treatment for AML patients
unfit for chemotherapy, 3 (37.5%) patients achieved a CR/CRh
- Time to CR/CRh was median 2.1 months and median duration of
CR/CRh was over 18 months, as of the cut-off date
The meeting abstract can be accessed here.
In the Phase 2 study, the registrational cohort enrolled 153
patients with mIDH1 R/R AML who received olutasidenib monotherapy
150 mg twice daily. The primary endpoint was a composite of
complete remission (CR) plus complete remission with partial
hematological recovery (CRh). The results demonstrated a rate of
CR/CRh of 35%, with a duration of response of 25.9 months.
On December 1, 2022, the U.S. Food
and Drug Administration (FDA) approved REZLIDHIA (olutasidenib)
capsules for the treatment of adult patients with R/R AML with a
susceptible IDH1 mutation as detected by an FDA-approved test.
REZLIDHIA became commercially available in the U.S. on December 22, 2022. REZLIDHIA was added to the
NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®) for acute myeloid leukemia (AML) on
January 13, 2023 as a recommended
targeted therapy for adult patients with R/R AML with isocitrate
dehydrogenase-1 (IDH1) mutation.
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 small molecule drugs that significantly improve the
lives of patients with hematologic disorders, cancer, and rare
immune diseases. 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.
- 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 Dec 2, 2021:
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
Rigel Forward Looking Statements
This press release
contains forward-looking statements relating to, among other
things, that olutasidenib may provide a meaningful benefit to
people with relapsed or refractory acute myeloid leukemia, our
ability to commercialize olutasidenib in the U.S. and identify
potential partners outside of the U.S., and our expectations
related to the potential and market opportunity of olutasidenib as
therapeutics for R/R AML and other conditions. 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
"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 that the
FDA, EMA 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 March 31, 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:
Rigel Pharmaceuticals, Inc.
650.624.1232
ir@rigel.com
Media:
David
Rosen
Argot Partners
212.600.1902
david.rosen@argotpartners.com
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