– The Primary Objective of Progression-Free
Survival Favored Selinexor over Placebo; Hazard Ratio of 0.60
(RECIST v1.1), Representing a 40% Reduction in Risk of Progression
or Death –
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today reported a successful outcome from
the Phase 2 portion of the SEAL study evaluating the activity of
selinexor (KPT-330), the Company's lead, novel, oral Selective
Inhibitor of Nuclear Export / SINE™ compound, in 57 patients with
previously treated, advanced unresectable dedifferentiated
liposarcoma. For the SEAL study’s primary endpoint of
progression-free survival (PFS), oral selinexor showed superiority
over placebo, achieving a hazard ratio (HR) of 0.60, representing a
40% reduction in the risk of progression or death. PFS was
assessed by Independent Central Radiological Review (ICRR) based on
RECIST v1.1.
In this randomized, blinded Phase 2 portion of
the study, oral selinexor demonstrated an expected and manageable
safety profile, primarily with nausea, anorexia and fatigue, low
levels of Grade 3/4 cytopenias, and no new or unexpected safety
signals identified. The majority of treatment-related adverse
events (AEs) were low grade and reversible with dose modifications
and/or standard supportive care. Importantly, the incidence
of infections in the selinexor arm (overall 29%; Grades ≥3, 0%) was
less than that reported in the placebo arm (overall 39%; Grade ≥3,
19%).
Additional efficacy assessments included PFS by
World Health Organization (WHO) response criteria, effects on
metabolic parameters via PET Scans, and PFS according to Choi
Criteria. PFS per WHO criteria achieved a HR of 0.84; the WHO
response criteria will not be included as part of the Phase 3 study
objectives. Karyopharm intends to submit detailed results from the
Phase 2 portion of the SEAL study for presentation at a future
medical meeting.
“There are few effective treatment options for
previously treated patients with recurrent dedifferentiated
liposarcoma and extending PFS is an important clinical goal because
the rapid progression of disease frequently results in early
mortality,” said Mrinal M. Gounder, MD, Attending Physician,
Sarcoma Service and Developmental Therapeutics Service, Memorial
Sloan Kettering Cancer Center, and Lead Investigator of the SEAL
trial. “These data are promising because they show
that oral selinexor is active and has the potential to prolong PFS
in this patient population, with an expected and manageable safety
profile. As an orally administered agent, selinexor could
be a welcome addition to the liposarcoma treatment landscape
and we look forward to further elucidating selinexor’s efficacy and
safety in the already ongoing Phase 3 portion of the SEAL
study.”
The Phase 3 portion of the SEAL study, which was
originally initiated in North America, is ongoing and has been
expanded to include Europe. In this blinded,
placebo-controlled Phase 3 study, up to 222 patients are expected
to be enrolled and randomized 2:1 to receive either oral selinexor,
(60mg fixed dose twice weekly) until disease progression or
intolerability, or placebo. Patients whose disease progresses
on placebo will be permitted to cross over to the selinexor
arm. The primary endpoint of the Phase 3 portion of the study
is PFS (RECIST v1.1) as assessed by the ICRR. The Phase 3
study design and primary endpoint of PFS were agreed to by the U.S.
Food and Drug Administration (FDA). Top-line data from the
Phase 3 portion of the SEAL study are anticipated by the end of
2019. Assuming a positive outcome, these data are expected to
support a New Drug Application for oral selinexor as a potential
new treatment for patients with advanced dedifferentiated
liposarcoma.
“Liposarcomas are difficult to treat solid
tumors that arise from the body’s fat tissue cells or their
precursors,” said Sharon Shacham, PhD, MBA, President and Chief
Scientific Officer of Karyopharm. “Dedifferentiated
liposarcoma is an aggressive form of the disease that is resistant
to both standard chemotherapy and radiation and has a particularly
high rate of recurrence following surgery. Most patients who
progress following surgery will ultimately succumb to their
disease, highlighting the significant unmet need that exists for
novel therapies. The FDA has confirmed their acceptance of
the proposed Phase 3 SEAL study design, including the PFS primary
endpoint, and agreed that positive results from this study could
support regulatory approval in this patient population.”
About Selinexor
Selinexor (KPT-330) is a first-in-class, oral
Selective Inhibitor of Nuclear Export / SINE™ compound. Selinexor
functions by binding with and inhibiting the nuclear export protein
XPO1 (also called CRM1), leading to the accumulation of tumor
suppressor proteins in the cell nucleus. This reinitiates and
amplifies their tumor suppressor function and is believed to lead
to the selective induction of apoptosis in cancer cells, while
largely sparing normal cells. To date, over 2,100 patients have
been treated with selinexor and it is currently being evaluated in
several mid- and later-phase clinical trials across multiple cancer
indications, including in multiple myeloma in a pivotal, randomized
Phase 3 study in combination with Velcade® (bortezomib) and
low-dose dexamethasone (BOSTON), in combination with low-dose
dexamethasone (STORM) and backbone therapies (STOMP), and in
diffuse large B-cell lymphoma (SADAL), and liposarcoma (SEAL),
among others. Additional Phase 1, Phase 2 and Phase 3 studies are
ongoing or currently planned, including multiple studies in
combination with one or more approved therapies in a variety of
tumor types to further inform the Company's clinical development
priorities for selinexor. Additional clinical trial information for
selinexor is available at www.clinicaltrials.gov.
About Karyopharm
Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq:KPTI) is a
clinical-stage pharmaceutical company focused on the discovery and
development of novel first-in-class drugs directed against nuclear
transport and related targets for the treatment of cancer and other
major diseases. Karyopharm's SINE™ compounds function by binding
with and inhibiting the nuclear export protein XPO1 (or CRM1). 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, which was
founded by Dr. Sharon Shacham, currently 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 the therapeutic potential of and potential clinical
development plans for Karyopharm's drug candidates, including
enrollment of certain trials and the timing of reporting of data
from such trials. Such statements are subject to numerous important
factors, risks and uncertainties that may cause actual events or
results to differ materially from Karyopharm’s current
expectations. For example, there can be no guarantee that any of
Karyopharm's SINE™ compounds, including selinexor (KPT-330), will
successfully complete necessary preclinical and 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 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: 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; 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 June 30, 2017,
which was filed with the Securities and Exchange Commission (SEC)
on August 8, 2017, 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.
Velcade® is a registered trademark of Takeda
Pharmaceutical Company Limited
Contacts:
Investors:Kimberly Minarovich(646)
368-8014kimberly@argotpartners.com
Gus Jenkins(646) 351-1067
gus@argotpartners.com
Media:Eliza Schleifstein(917)
763-8106eliza@argotpartners.com
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