-- Growing body of data on
REZLIDHIA® (olutasidenib) in mIDH1 relapsed or
refractory (R/R) acute myeloid leukemia (AML) patients --
-- New data on olutasidenib in patients with
mIDH1 myelodysplastic syndromes/neoplasms (MDS) --
SOUTH
SAN FRANCISCO, Calif., Nov. 2, 2023
/PRNewswire/ -- Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL)
today announced the upcoming presentation of four posters
highlighting data from their commercial and clinical-stage
hematology-oncology portfolio at the 65th American
Society of Hematology (ASH) Annual Meeting and Exposition being
held December 9-12, 2023, in
San Diego, California and
virtually.
"We are encouraged by the collective data supporting the
potential use of REZLIDHIA in various mIDH1 AML patient
populations, including those that are relapsed or refractory to
hematopoietic stem cell transplant, ivosidenib, or venetoclax.
These data continue to indicate this treatment could meaningfully
improve the lives of underserved patients living with mIDH1
R/R AML," said Raul Rodriguez,
Rigel's president and CEO. "We are also excited by the compelling
data in patients with mIDH1 MDS and look forward to
evaluating this potential opportunity further. On top of the
olutasidenib data, we are delighted to share other updates and data
across our development portfolio, demonstrating our presence in the
hematology-oncology space."
Details of the poster presentations and publication at the ASH
Annual Meeting are as follows:
Poster Presentations
Abstract #: 2888
Title: Olutasidenib for the Treatment of mIDH1 Acute Myeloid
Leukemia in Patients Relapsed or Refractory to Hematopoietic Stem
Cell Transplant, Prior mIDH1 Inhibitor, or Venetoclax
Presenter: Jorge E. Cortes,
M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair
in Cancer, and Phase 2 Trial Investigator
Session Name: 615. Acute Myeloid Leukemias: Commercially
Available Therapies, Excluding Transplantation and Cellular
Immunotherapies: Poster II
Date: Sunday, December 10,
2023
Presentation Time: 6:00-8:00 PM
PT
Location: San Diego
Convention Center, Halls G-H
- This poster reports post hoc analyses from the
registrational Phase 1/2 trial of olutasidenib, a small molecule,
oral, mutated-IDH1 (mIDH1) inhibitor approved for the treatment of
relapsed/refractory (R/R) acute myeloid leukemia (AML),
alone or in combination with azacitidine in a subset of patients
with mIDH1 R/R AML or MDS that were R/R to previous hematopoietic
stem cell transplant (HSCT), ivosidenib (IVO) or venetoclax
(VEN).
- In the post-HSCT group (n=31), 19% of these patients had a
complete response (CR), and 10% of patients had a CR with
incomplete count recovery (CRi) resulting in a 29% composite
complete remission (CRc) rate.
- In the post-IVO group (n=9), 22% achieved a response, all of
which were CR.
- In the post-VEN group
(n=20), response rates included CR in 30% of patients, CR with
partial hematologic recovery (CRh) in 5%, and CRi in 10% resulting
in a CRc of 45% and an ORR of 45%.
- The analyses suggests that olutasidenib alone or in
combination with azacitidine may induce complete remissions in
patients with mIDH1 AML or MDS that are R/R to VEN, IVO or even HSCT.
Abstract #: 1872
Title: Olutasidenib Alone or in Combination with Azacitidine
Induces Durable Complete Remissions in Patients with mIDH1
Myelodysplastic Syndromes/Neoplasms (MDS)
Presenter: Jorge E. Cortes,
M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair
in Cancer, and Phase 2 Trial Investigator
Session Name: 637. Myelodysplastic Syndromes – Clinical and
Epidemiological: Poster I
Date: Saturday, December 9,
2023
Presentation Time: 5:30-7:30 PM
PT
Location: San Diego
Convention Center, Halls G-H
- This poster reports the results from a Phase 1/2 trial of
olutasidenib alone or in combination with azacitidine in a subset
of 22 patients with mIDH1 MDS.
- For the pooled Phase 1 and 2 data, 27% of patients achieved
CR and 32% of patients achieved marrow CR with no partial
remissions, generating a 59% overall response rate. The median time
to response was 2.0 months and the median duration of response was
not reached at 30.1+ months.
- All patients with MDS experienced at least 1
treatment-emergent adverse event (TEAE). The most frequent
TEAEs in the study were nausea, constipation, vomiting,
thrombocytopenia, neutropenia, diarrhea, and fatigue. Grade 3 TEAEs
occurred in 19/22 (86%) patients, and Grade 4 TEAEs in 9/22 (41%).
The most frequent Grade 3/4 TEAEs reported were
cytopenias.
- Olutasidenib, both as monotherapy and in combination with
azacitidine, induced durable remissions in patients with
intermediate-, high-, or very high-risk MDS. Patients had varying
treatment backgrounds, including treatment-naïve and up to four
prior regimens. This treatment had a tolerable and manageable
safety profile.
- These encouraging results, which warrant further
investigation with a larger number of patients, showed that
olutasidenib had clinically meaningful activity in patients with
mIDH1 MDS.
Abstract #: 3247
Title: Phase 1b Trial of IRAK
1/4 Inhibition for Low-Risk Myelodysplastic Syndrome
Refractory/Resistant to Prior Therapies: A Trial In Progress
Presenter: Guillermo
Garcia-Manero, M.D., The University of
Texas MD Anderson Cancer Center, Department of Leukemia,
Houston, TX
Session Name: 637. Myelodysplastic Syndromes – Clinical and
Epidemiological: Poster II
Date: Sunday, December 10,
2023
Presentation Time: 6:00-8:00 PM
PT
Location: San Diego
Convention Center, Halls G-H
- This trial in progress poster provides an overview of the
study design of the ongoing Phase 1b
trial evaluating R2891, a potent and selective inhibitor
of IRAK1 and IRAK4 kinases, in patients with low-risk
myelodysplastic syndrome (LR-MDS) relapsed or
refractory to prior therapies. The inhibition of
IRAK1/4 is a potential target for the treatment of LR-MDS by
decreasing inflammation and cell death within the bone marrow,
allowing for restoration of hematopoiesis.
Abstract #: 2578
Title: Long-Term Treatment with Fostamatinib in Japanese
Patients with Primary Immune Thrombocytopenia: An Open-Label
Extension Study Following a Phase 3 Placebo-Controlled,
Double-Blind, Parallel-Group Study
Session Name: 311. Disorders of Platelet Number or Function:
Clinical and Epidemiological: Poster II
Date: Sunday, December 10,
2023
Presentation Time: 6:00-8:00 PM
PT
Location: San Diego
Convention Center, Halls G-H
- This poster highlights the long-term efficacy and safety of
fostamatinib in Japanese patients with primary immune
thrombocytopenia (ITP), along with the feasibility of
glucocorticoid reduction/discontinuation during
fostamatinib treatment and a lack of bleeding events
after abrupt discontinuation of fostamatinib. These
results support the use of fostamatinib as a second-line treatment
in patients with primary ITP.
The conference abstracts can be accessed here.
To learn more about Rigel Pharmaceuticals and their clinical and
commercial hematology/oncology portfolio visit Booth #2805 during
ASH 2023.
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 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 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.
- 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 olutasidenib as
therapeutics for R/R AML and other conditions, the potential and
market opportunity of fostamatinib as therapeutics for ITP and
other conditions, the commercialization of fostamatinib or
olutasidenib in the U.S. and international markets, and Rigel's
ability to further develop its clinical stage and early-stage
product candidates and Rigel's partnering effort, including the
progress of Phase 1b clinical trial
of R289 for the treatment of lower-risk myeloid dysplastic
syndrome, and an open-label extension study of fostamatinib for
long-term treatment of Japanese patients with primary 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
"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 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 commercialization and marketing
of fostamatinib or olutasidenib; risks that the FDA, European
Medicines Agency, PMDA or other regulatory authorities may make
adverse decisions regarding fostamatinib or olutasidenib; risks
that clinical trials may not be predictive of real-world results or
of results in subsequent clinical trials; risks that fostamatinib
or 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 June 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.
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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