- Oral presentation of final five-year results from the
registrational Phase 2 trial in R/R mIDH1 AML patients reinforces
REZLIDHIA® (olutasidenib) efficacy in heavily pretreated
patients, including those receiving prior venetoclax
- Other key posters further support the efficacy of
REZLIDHIA® (olutasidenib) in elderly,
transplant-eligible, and post-MPN patients with AML
SOUTH
SAN FRANCISCO, Calif., May 23, 2024
/PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today
announced upcoming presentations from their commercial and
clinical-stage hematology and oncology portfolio at the 2024
American Society of Clinical Oncology (ASCO) Annual Meeting and
European Hematology Association (EHA) 2024 Hybrid Congress. The
ASCO Annual Meeting is being held online and in person in
Chicago, Illinois from
May 31 to June 4, 2024. The EHA2024
Congress is being held online and in person in Madrid, Spain from June
13 to June 16, 2024.
Rigel's presentations will include data for
REZLIDHIA® (olutasidenib), for the treatment of mutated
isocitrate dehydrogenase-1 (mIDH1) acute myeloid leukemia (AML),
and TAVALISSE® (fostamatinib), for the treatment of
chronic immune thrombocytopenia (ITP), along with an overview of
the ongoing Phase 1b trial evaluating
R2891, a potent and selective inhibitor of IRAK1 and
IRAK4, in patients with lower-risk myelodysplastic syndrome
(LR-MDS) who are refractory or resistant to prior therapies.
"We are excited to present new data on REZLIDHIA that adds to
the growing body of evidence supporting its efficacy and safety in
patients with mIDH1 AML, including difficult to treat patient
populations. The five-year data from the registrational Phase 2
trial continue to demonstrate that REZLIDHIA induces rapid and
durable responses. In addition, new analyses support the benefit it
may provide to elderly patients," said Raul
Rodriguez, Rigel's president and CEO. "The collective data
to be presented at ASCO and EHA underscore the strength and
compelling science of our hematology and oncology portfolio."
Highlights from the robust REZLIDHIA (olutasidenib) data
published include:
- An additional two years of data, beyond the results that led to
FDA approval of olutasidenib, further demonstrates the durable
responses observed with olutasidenib in heavily pretreated patients
with mIDH1 AML, including those relapsed or refractory (R/R) to
prior venetoclax. The safety profile was consistent with what was
previously reported.
- Olutasidenib was generally well tolerated in elderly patients
with R/R mIDH1 AML and induced durable remissions. Despite the
challenges of treating elderly patients who had already failed
prior AML treatment, the results suggest that elderly patients can
benefit from therapy with olutasidenib.
- Olutasidenib was effective in achieving remission in patients
with mIDH1 R/R AML and served as a bridging strategy towards
potentially curative allogeneic transplantation in a substantial
subset of these previously ineligible patients.
- Olutasidenib was well tolerated in a subset of patients with
post-myeloproliferative neoplasms (MPN) mlDH1 AML, a patient
population often associated with poor responses to available
therapies.
Data from the TAVALISSE (fostamatinib) observational study
provides greater insight into use in the real-world setting:
- In the study, fostamatinib demonstrated efficacy and safety as
second-line therapy for ITP. Fostamatinib allowed successful
tapering and discontinuation of corticosteroids while maintaining
platelet counts above 50,000/μL.
ASCO Annual Meeting abstracts may be accessed online via
https://www.asco.org/abstracts. Details of the poster presentations
and publications are as follows:
ASCO Poster Presentations
Monday, June 3, 2024,
9:00am to 12:00pm
CT
Abstract #: 6528
Title: Olutasidenib for Mutated IDH1 Acute
Myeloid Leukemia: Final Five-Year Results from the Phase 2 Pivotal
Cohort
Presenter: Jorge E. Cortes, M.D.
Abstract #: 6527
Title: Safety and Efficacy of Olutasidenib Treatment in
Elderly Patients with Relapsed/Refractory mIDH1 Acute
Myeloid Leukemia
Presenter: Stéphane de Botton, M.D., Ph.D.
Abstract #: TPS6591
Title: Phase 1b Trial of
IRAK 1/4 Inhibition for Lower-Risk Myelodysplastic Syndrome
Refractory/Resistant to Prior Therapies: A Trial in Progress
Presenter: Guillermo Garcia-Manero, M.D.
ASCO Publications
Abstract #: e18516
Title: Patients with Relapsed/Refractory mIDH1
AML Who Proceeded to Transplant After Olutasidenib Treatment
Authors: Stéphane de Botton, M.D., Ph.D.; Justin M
Watts, M.D.; Brian A Jonas, M.D., Ph.D.; Mwe Mwe Chao, M.D.; Jorge Cortes, M.D.
Abstract #: e23289
Title: Real-World Experience with Fostamatinib in
Patients with Immune Thrombocytopenia: Results of an Observational
Study (FORTE)
Authors: Ruchika Goel, M.D., MPH; Waqas Azhar, M.D.; Robert P. Numerof, Ph.D.; Donna Chow, MS; Bhavesh
Shah, M.D.
EHA2024 Congress abstracts may be accessed online via the EHA
Library. Details of the poster presentations and publications are
as follows:
EHA Oral Presentation
Saturday, June 15, 17:30 to 17:45 CEST
Abstract #:
S144
Title: Olutasidenib for Mutated IDH1 Acute Myeloid
Leukemia: Final Five-year Results from the Phase 2 Pivotal
Cohort
Presenter: Jorge E. Cortes,
M.D.
EHA Poster Presentations
Friday, June 14, 18:00 to 19:00 CEST
Abstract #:
P605
Title: Olutasidenib Demonstrates Clinical Activity in
Mutated IDH1 Acute Myeloid Leukemia (AML) Secondary to
Myeloproliferative Neoplasms (MPN)
Presenter: Stéphane de Botton, M.D., Ph.D.
Abstract #: P614
Title: Response to Olutasidenib in Patients with Acute
Myeloid Leukemia (AML) Following Venetoclax Failure
Presenter: Jorge E. Cortes, M.D.
Abstract #: P611
Title: Safety and Efficacy of Olutasidenib Treatment in
Elderly Patients with Relapsed/Refractory mIDH1 Acute
Myeloid Leukemia
Presenter: Stéphane de Botton, M.D., Ph.D.
Abstract #: P1373
Title: Olutasidenib as Bridge-to-Transplant Treatment
in Patients with Relapsed/Refractory mIDH1 Acute Myeloid
Leukemia (AML)
Presenter: Stéphane de Botton, M.D., Ph.D.
EHA Publications
Abstract #: PB3344
Title: Real-World Experience with Fostamatinib in
Patients with Immune Thrombocytopenia: Results of an Observational
Study (FORTE)
Authors: Ruchika Goel, M.D., MPH; Drew Provan, M.D.; Francois Di Trapani, Pharm.D.
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 there will be about 20,800 new cases in the United States, most in adults, in
2024.2
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 ITP
In patients with ITP (immune
thrombocytopenia), the immune system attacks and destroys the
body's own blood platelets, which play an active role in blood
clotting and healing. Common symptoms of ITP are excessive bruising
and bleeding. People suffering with chronic ITP may live with an
increased risk of severe bleeding events that can result in serious
medical complications or even death. Current therapies for ITP
include steroids, blood platelet production boosters (TPO-RAs), and
splenectomy. However, not all patients respond to existing
therapies. As a result, there remains a significant medical need
for additional treatment options for patients with ITP.
About R289
R289 is a prodrug of R835, an IRAK1/4 dual inhibitor, which
has been shown in preclinical studies to block inflammatory
cytokine production in response to toll-like receptor (TLR) and
interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs
play a critical role in the innate immune response and
dysregulation of these pathways can lead to various inflammatory
conditions. Chronic stimulation of both these receptor systems is
thought to cause the pro-inflammatory environment in the bone
marrow responsible for persistent cytopenias in lower-risk MDS
patients.5
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
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.TAVALISSEUSPI.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 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.
- R289 is an investigational compound not approved by the
FDA.
- 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 17,
2024. Accessed Feb. 19,
2024: 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 19,
2024: 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
- Sallman DA et al. Unraveling the Pathogenesis of MDS:
The NLRP3 Inflammasome and Pyroptosis Drive the MDS Phenotype.
Front Oncol. June 16, 2016.
DOI: https://doi.org/10.3389/fonc.2016.0015
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 heavily pretreated R/R mIDH1 AML patients including
those receiving prior venetoclax treatment, the use of olutasidenib
in treating elderly, transplant-eligible, and post-MPN patients
with AML, and the use of fostamatinib as a second-line
therapy for ITP. 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 "may", "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 Annual Report on Form 10-K for
the year ended December 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.
Contact for Investors & Media:
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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