- Review article examines the preclinical and clinical
development, and the role of olutasidenib in the mIDH1 AML
treatment landscape.
- Authors conclude, "The approval of olutasidenib is a critical
addition to the mIDH1 AML treatment landscape with
encouragingly durable responses."
SOUTH
SAN FRANCISCO, Calif., June 6, 2023
/PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL)
today announced an expert review article in Blood
Advances examining the development path and positioning of
REZLIDHIA® (olutasidenib), a potent, selective, oral,
small-molecule inhibitor of mutant isocitrate dehydrogenase-1
(mIDH1)1, in the
mIDH1 relapsed/refractory (R/R) acute myeloid leukemia
(AML) treatment landscape.
"The compelling safety and efficacy results observed in
REZLIDHIA trials to date, marked by encouragingly durable
responses, represent an important advance for mIDH1 R/R AML
patients and treating physicians," said Justin Watts, M.D., Lead Author and Associate
Professor of Medicine, Division of Hematology, Chief, Leukemia
Section at the University of Miami
Health System. "These data are particularly supportive of the use
of REZLIDHIA in mIDH1 R/R AML patients who have failed
intensive chemotherapy or venetoclax plus HMA combination therapy.
The results validate ongoing studies evaluating olutasidenib in
frontline and R/R settings as a monotherapy and in combination with
azacitidine with or without prior exposure to HMA or IDH1
inhibitor."
"We are pleased with the growing body of evidence and thought
leader support for REZLIDHIA as a differentiated and potentially
market-leading therapy for mIDH1 R/R AML patients," said
Raul Rodriguez, Rigel's president
and CEO. "We remain committed to delivering this important
treatment option to mIDH1 R/R AML patients and look forward
to data from the ongoing studies of REZLIDHIA in broader
mIDH1 AML treatment settings."
Key points from the paper are summarized below:
- REZLIDHIA demonstrated highly durable remission rates,
representing a critical addition to the mIDH1 AML treatment
landscape
- The available data support the use of REZLIDHIA as monotherapy
in R/R AML patients who have failed intensive chemotherapy or
venetoclax plus HMA combination therapy
- The authors state that the choice of which IDH1 inhibitor to
use first in these patients is not yet clear, although given the
available data REZLIDHIA is recommended in venetoclax plus HMA
failures
-
- Among the 12 patients with prior exposure to venetoclax, the
ORR was 50% with four patients achieving CR/CRh (33%; 95% CI,
9.9–65.1) and two patients had CRi
- Ongoing studies (NCT02719574) could clarify the role of
REZLIDHIA in treatment naïve mIDH1 AML (including when
given in combination with azacitidine) and in R/R
mIDH1 AML with prior IDH1 inhibitor exposure. Further
studies assessing maintenance, triplet therapy, and sequencing with
venetoclax and azacitidine are being considered.
The paper, titled "Olutasidenib: from Bench to Bedside," was
published online in Blood Advances and can be accessed
here.
Rigel announced a peer-reviewed publication of data in Blood
Advances in February 2023,
which summarizes clinical results from the Phase 2
registrational trial of REZLIDHIA in patients with mIDH1 R/R
AML.
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
View original content to download
multimedia:https://www.prnewswire.com/news-releases/rigel-announces-second-rezlidhia-olutasidenib-publication-in-blood-advances-301843134.html
SOURCE Rigel Pharmaceuticals, Inc.