NEWTON, Mass., Nov. 25, 2020 /PRNewswire/ -- Karyopharm
Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical
company pioneering novel cancer therapies, today announced that
following a pre-specified interim futility analysis for the ongoing
Phase 3 SIENDO study, the Data and Safety Monitoring Board (DSMB)
has recommended that the study should continue, as previously
planned, without the need for adding additional patients to the
trial or amending the study protocol.
"We are very excited that the SIENDO study has passed its
planned futility analysis and that the study will continue as
planned," said Sharon Shacham, PhD,
MBA, President and Chief Scientific Officer of Karyopharm. "We
believe this is an encouraging development for the study, and more
importantly, for patients and families in need of novel treatment
options for advanced or recurrent endometrial cancer. There are
currently no approved therapies in the maintenance setting for
patients with advanced endometrial cancer, making the future trial
results from the SIENDO study, particularly important. We expect to
report top-line data from this study in the second half of
2021."
The SIENDO study is an ongoing multicenter, blinded,
placebo-controlled, randomized Phase 3 study evaluating the
efficacy and safety for front-line maintenance therapy with XPOVIO
in patients with advanced or recurrent endometrial cancer.
Participants with primary stage IV or recurrent disease who had a
partial or complete response after a single line of at least 12
weeks of standard taxane-platinum combination chemotherapy are
randomized in a 2:1 manner to receive either maintenance therapy of
80mg of XPOVIO taken once per week or placebo, until
disease progression. The study is expected to enroll approximately
248 patients. The primary endpoint in the study is progression free
survival (PFS) with the goal of the study demonstrating a hazard
ratio of 0.6. As of the date of the planned futility analysis,
approximately 109 patients had been enrolled in the trial.
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear
Export (SINE) compound. XPOVIO functions by selectively binding to
and inhibiting the nuclear export protein exportin 1 (XPO1, also
called CRM1). XPOVIO blocks the nuclear export of tumor suppressor,
growth regulatory and anti-inflammatory proteins, leading to
accumulation of these proteins in the nucleus and enhancing their
anti-cancer activity in the cell. The forced nuclear retention of
these proteins can counteract a multitude of the oncogenic pathways
that, unchecked, allow cancer cells with severe DNA damage to
continue to grow and divide in an unrestrained fashion. Karyopharm
received accelerated U.S. Food and Drug Administration (FDA)
approval of XPOVIO in July 2019 in
combination with dexamethasone for the treatment of adult patients
with relapsed or refractory multiple myeloma (RRMM) who have
received at least four prior therapies and whose disease is
refractory to at least two proteasome inhibitors, at least two
immunomodulatory agents, and an anti-CD38 monoclonal antibody.
Karyopharm has also submitted a Marketing Authorization Application
(MAA) to the European Medicines Agency (EMA) with a request for
conditional approval of selinexor in this same RRMM indication.
Karyopharm's supplemental New Drug Application (sNDA) requesting an
expansion of its current indication to include the treatment for
patients with multiple myeloma after at least one prior line of
therapy has been accepted for filing by the FDA. In June 2020, Karyopharm received accelerated FDA
approval of XPOVIO for its second indication in adult patients with
relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not
otherwise specified, including DLBCL arising from follicular
lymphoma, after at least 2 lines of systemic therapy. Selinexor is
also being evaluated in several other mid-and later-phase clinical
trials across multiple cancer indications, including as a potential
backbone therapy in combination with approved myeloma therapies
(STOMP), in liposarcoma (SEAL) and in endometrial cancer (SIENDO),
among others. Additional Phase 1, Phase 2 and Phase 3 studies are
ongoing or currently planned, including multiple studies in
combination with approved therapies in a variety of tumor types to
further inform Karyopharm's clinical development priorities for
selinexor. Additional clinical trial information for selinexor is
available at www.clinicaltrials.gov.
For more information about Karyopharm's products or clinical
trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
Email: medicalinformation@karyopharm.com
IMPORTANT SAFETY INFORMATION
Thrombocytopenia: XPOVIO can cause life-threatening
thrombocytopenia, potentially leading to hemorrhage.
Thrombocytopenia was reported in patients with multiple myeloma
(MM) and developed or worsened in patients with DLBCL.
Thrombocytopenia is the leading cause of dosage modifications.
Monitor platelet counts at baseline and throughout treatment.
Monitor more frequently during the first 3 months of treatment.
Institute platelet transfusion and/or other treatments as
clinically indicated. Monitor patients for signs and symptoms of
bleeding and evaluate promptly. Interrupt, reduce dose, or
permanently discontinue based on severity of adverse reaction.
Neutropenia: XPOVIO can cause life-threatening
neutropenia, potentially increasing the risk of infection.
Neutropenia and febrile neutropenia occurred in patients with MM
and in patients with DLBCL.
Obtain white blood cell counts with differential at baseline and
throughout treatment. Monitor more frequently during the first 3
months of treatment. Monitor patients for signs and symptoms of
concomitant infection and evaluate promptly. Consider supportive
measures, including antimicrobials and growth factors (e.g.,
G-CSF). Interrupt, reduce dose, or permanently discontinue based on
severity of adverse reaction (AR).
Gastrointestinal Toxicity: XPOVIO can cause severe
gastrointestinal toxicities in patients with MM and DLBCL.
Nausea/Vomiting: Provide prophylactic antiemetics.
Administer 5-HT3 receptor antagonists and other anti-nausea agents
prior to and during treatment with XPOVIO. Interrupt, reduce dose,
or permanently discontinue based on severity of ARs. Administer
intravenous fluids to prevent dehydration and replace electrolytes
as clinically indicated.
Diarrhea: Interrupt, reduce dose, or permanently
discontinue based on severity of ARs. Provide standard
anti-diarrheal agents, administer intravenous fluids to prevent
dehydration, and replace electrolytes as clinically indicated.
Anorexia/Weight Loss: Monitor weight, nutritional
status, and volume status at baseline and throughout treatment.
Monitor more frequently during the first 3 months of treatment.
Interrupt, reduce dose, or permanently discontinue based on
severity of ARs. Provide nutritional support, fluids, and
electrolyte repletion as clinically indicated.
Hyponatremia: XPOVIO can cause severe or
life-threatening hyponatremia. Hyponatremia developed in patients
with MM and in patients with DLBCL.
Monitor sodium level at baseline and throughout treatment.
Monitor more frequently during the first 2 months of treatment.
Correct sodium levels for concurrent hyperglycemia (serum glucose
>150 mg/dL) and high serum paraprotein levels. Assess hydration
status and manage hyponatremia per clinical guidelines, including
intravenous saline and/or salt tablets as appropriate and dietary
review. Interrupt, reduce dose, or permanently discontinue based on
severity of the AR.
Serious Infection: XPOVIO can cause
serious and fatal infections. Most infections were not associated
with Grade 3 or higher neutropenia. Atypical infections reported
after taking XPOVIO include, but are not limited to, fungal
pneumonia and herpesvirus infection.
Monitor for signs and symptoms of infection, and evaluate and
treat promptly.
Neurological Toxicity: XPOVIO can cause
life-threatening neurological toxicities.
Coadministration of XPOVIO with other products that cause
dizziness or mental status changes may increase the risk of
neurological toxicity.
Advise patients to refrain from driving and engaging in
hazardous occupations or activities, such as operating heavy or
potentially dangerous machinery, until the neurological toxicity
fully resolves. Optimize hydration status, hemoglobin level, and
concomitant medications to avoid exacerbating dizziness or mental
status changes. Institute fall precautions as appropriate.
Embryo-Fetal Toxicity: XPOVIO can cause fetal harm
when administered to a pregnant woman.
Advise pregnant women of the potential risk to a fetus. Advise
females of reproductive potential and males with a female partner
of reproductive potential to use effective contraception during
treatment with XPOVIO and for 1 week after the last dose.
ADVERSE REACTIONS
The most common adverse reactions
(ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue,
nausea, anemia, decreased appetite, decreased weight, diarrhea,
vomiting, hyponatremia, neutropenia, leukopenia, constipation,
dyspnea, and upper respiratory tract infection.
The most common ARs, excluding laboratory abnormalities, in ≥20%
of patients with DLBCL are fatigue, nausea, diarrhea, appetite
decrease, weight decrease, constipation, vomiting, and pyrexia.
Grade 3-4 laboratory abnormalities in ≥15% of patients included
thrombocytopenia, lymphopenia, neutropenia, anemia, and
hyponatremia. Grade 4 laboratory abnormalities in ≥5% were
thrombocytopenia, lymphopenia, and neutropenia.
In patients with MM, fatal ARs occurred in 9% of patients.
Serious ARs occurred in 58% of patients. Treatment discontinuation
rate due to ARs was 27%. The most frequent ARs requiring permanent
discontinuation in ≥4% of patients included fatigue, nausea, and
thrombocytopenia.
In patients with DLBCL, fatal ARs occurred in 3.7% of patients
within 30 days, and 5% of patients within 60 days of last
treatment; the most frequent fatal AR was infection (4.5% of
patients). Serious ARs occurred in 46% of patients; the most
frequent serious AR was infection. Discontinuation due to ARs
occurred in 17% of patients.
USE IN SPECIFIC POPULATIONS
In MM, no overall
difference in effectiveness of XPOVIO was observed in patients
>65 years old when compared with younger patients. Patients ≥75
years old had a higher incidence of discontinuation due to an AR
than younger patients, a higher incidence of serious ARs, and a
higher incidence of fatal ARs.
Clinical studies in patients with relapsed or refractory DLBCL
did not include sufficient numbers of patients aged 65 and over to
determine whether they respond differently from younger
patients.
The effect of end-stage renal disease
(CLCR <15 mL/min) or hemodialysis on XPOVIO
pharmacokinetics is unknown.
To report SUSPECTED ADVERSE REACTIONS,
contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see XPOVIO Full Prescribing Information available
at www.XPOVIO.com.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a
commercial-stage pharmaceutical company pioneering novel cancer
therapies and dedicated to the discovery, development, and
commercialization of novel first-in-class drugs directed against
nuclear export and related targets for the treatment of cancer and
other major diseases. Karyopharm's Selective Inhibitor of Nuclear
Export (SINE) compounds function by binding with and inhibiting the
nuclear export protein XPO1 (or CRM1). Karyopharm's lead compound,
XPOVIO® (selinexor), received accelerated approval from the U.S.
Food and Drug Administration (FDA) in July
2019 in combination with dexamethasone as a treatment for
patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a
treatment for patients with relapsed or refractory diffuse large
B-cell lymphoma. A Marketing Authorization Application for
selinexor for patients with heavily pretreated multiple myeloma is
also currently under review by the European Medicines Agency. In
addition to single-agent and combination activity against a variety
of human cancers, SINE compounds have also shown biological
activity in models of neurodegeneration, inflammation, autoimmune
disease, certain viruses and wound-healing. Karyopharm has several
investigational programs in clinical or preclinical development.
For more information, please visit www.karyopharm.com.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of
1995. Such forward-looking statements include those regarding
Karyopharm's expectations and plans relating to XPOVIO for the
treatment of patients with advanced endometrial cancer;
commercialization of XPOVIO or any of its drug candidates and the
commercial performance of XPOVIO; submissions to, and the review
and potential approval of selinexor by, regulatory authorities,
including the Company's regulatory strategy, the anticipated
availability of data to support such submissions, timing of such
submissions and actions by regulatory authorities and the potential
availability of accelerated approval pathways; the expected design
of the Company's clinical trials; and the therapeutic potential of
and potential clinical development plans for Karyopharm's drug
candidates, especially selinexor. Such statements are subject to
numerous important factors, risks and uncertainties, many of which
are beyond Karyopharm's control, that may cause actual events or
results to differ materially from Karyopharm's current
expectations. For example, there can be no guarantee that
Karyopharm will successfully commercialize XPOVIO; that regulators
will agree that selinexor qualifies for conditional approval in the
E.U. as a result of data from the STORM study or confirmatory
approval in the U.S. or EU based on the BOSTON study in patients with relapsed or
refractory multiple myeloma; or that any of Karyopharm's
drug candidates, including selinexor, will successfully
complete necessary clinical development phases or that development
of any of Karyopharm's drug candidates will continue. Further,
there can be no guarantee that any positive developments in the
development or commercialization of Karyopharm's drug candidate
portfolio will result in stock price appreciation. Management's
expectations and, therefore, any forward-looking statements in this
press release could also be affected by risks and uncertainties
relating to a number of other factors, including the following: the
risk that the COVID-19 pandemic could disrupt Karyopharm's business
more severely than it currently anticipates, including by
negatively impacting sales of XPOVIO, interrupting or delaying
research and development efforts, impacting the ability to procure
sufficient supply for the development and commercialization of
selinexor or other product candidates, delaying ongoing or planned
clinical trials, impeding the execution of business plans, planned
regulatory milestones and timelines, or inconveniencing patients;
the adoption of XPOVIO in the commercial marketplace, the timing
and costs involved in commercializing XPOVIO or any of Karyopharm's
drug candidates that receive regulatory approval; the ability to
retain regulatory approval of XPOVIO or any of Karyopharm's drug
candidates that receive regulatory approval; Karyopharm's results
of clinical trials and preclinical studies, including subsequent
analysis of existing data and new data received from ongoing and
future studies; the content and timing of decisions made by the
U.S. Food and Drug Administration and other regulatory authorities,
investigational review boards at clinical trial sites and
publication review bodies, including with respect to the need for
additional clinical studies; the ability of Karyopharm or its third
party collaborators or successors in interest to fully perform
their respective obligations under the applicable agreement and the
potential future financial implications of such agreement;
Karyopharm's ability to obtain and maintain requisite regulatory
approvals and to enroll patients in its clinical trials; unplanned
cash requirements and expenditures; development of drug candidates
by Karyopharm's competitors for diseases in which Karyopharm is
currently developing its drug candidates; and Karyopharm's ability
to obtain, maintain and enforce patent and other intellectual
property protection for any drug candidates it is developing. These
and other risks are described under the caption "Risk Factors" in
Karyopharm's Quarterly Report on Form 10-Q for the quarter ended
September 30, 2020, which was filed with the Securities and
Exchange Commission (SEC) on November 2, 2020, and in other
filings that Karyopharm may make with the SEC in the future. Any
forward-looking statements contained in this press release speak
only as of the date hereof, and, except as required by law,
Karyopharm expressly disclaims any obligation to update any
forward-looking statements, whether as a result of new information,
future events or otherwise.
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