- Olutasidenib induced durable composite complete remission in
43.8% of patients relapsed or refractory to prior venetoclax-based
regimens
- Safety was consistent with the overall profile of
olutasidenib
- Olutasidenib may offer a valuable treatment option for
patients with mIDH1 previously treated with venetoclax
SOUTH
SAN FRANCISCO, Calif., April 4,
2024 /PRNewswire/ -- Rigel Pharmaceuticals, Inc.
(Nasdaq: RIGL) today announced a peer-reviewed publication
in Leukemia & Lymphoma on 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.
"Venetoclax in combination with a hypomethylating agent is
currently standard treatment for patients with newly diagnosed AML
who are unfit for intensive chemotherapy, including those with
mIDH1. When this therapy fails, patients historically have
had limited treatment options and poor prognoses," 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. "The findings from these analyses suggest that
REZLIDHIA may provide an effective treatment for patients with AML
following failure of venetoclax combination therapy. REZLIDHIA
induced durable remissions consistent with those observed in the
pivotal trial and had a favorable tolerability profile in this
challenging to treat patient population, representing a valuable
treatment option."
"These data support REZLIDHIA's efficacy and well-characterized
safety profile in patients with mIDH1 R/R AML who had
previously been treated with venetoclax combination regimens," said
Raul Rodriguez, Rigel's president
and CEO. "These analyses are important because they provide
valuable insights into the potential benefit of REZLIDHIA in
different segments of the mIDH1 R/R AML patient
population."
Key points from the paper are summarized below:
- Olutasidenib alone or in combination with azacitidine
demonstrated potential efficacy in patients with AML following
failure of venetoclax combination therapy
- Of the 18 patients with prior venetoclax treatment, 10 were
relapsed, 6 were refractory, and 2 had complete remission with
incomplete hematologic recovery (CRi) to a venetoclax
combination
- Of the 16 R/R patients, 7 (43.8%) achieved a composite complete
remission (CRc), 4 (25%) achieved complete remission (CR), and 1
(6.3%) achieved CR with partial hematologic recovery (CRh). Both
patients with CRi at study entry achieved CR
- Median time to CRc was 1.9 months (range 1-2.8). As of the data
cut-off (June 18, 2021), median
duration of CRc was not reached (range, 1.2-NR, ongoing at 30.4+
months)
- Red blood cell and platelet transfusion independence was
achieved in 2/12 (17%) and 2/7 (29%) transfusion-dependent R/R
patients at baseline, respectively
- Safety was consistent with the overall profile of
olutasidenib
The paper, titled "Olutasidenib in post-venetoclax patients with
mutant isocitrate dehydrogenase 1 (mIDH1) acute myeloid
leukemia (AML)," was published online in Leukemia &
Lymphoma and can be accessed here.
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 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.
- 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
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 Post-Venetoclax Patients with Mutant IDH1 AML. 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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