-- 29.6% Overall Response Rate Including
9.6% Complete Response Rate --
Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today reported positive top-line results
from the Phase 2b SADAL (
Selinexor
Against
Diffuse
Aggressive
Lymphoma) study
evaluating selinexor, the Company’s first-in-class, oral Selective
Inhibitor of Nuclear Export (SINE) compound, in patients with
relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after
at least two prior multi-agent therapies and who are ineligible for
transplantation, including high dose chemotherapy with stem cell
rescue. The data were highlighted in a poster presentation at the
American Society of Hematology (ASH) 2018 Annual Meeting in San
Diego. For the SADAL study’s primary endpoint, single-agent
selinexor achieved a 29.6% overall response rate (ORR), which
included a 9.6% complete response (CR) rate in patients with
heavily pretreated relapsed or refractory DLBCL. Key secondary
endpoints included a median duration of response (DOR, in the
responding patients) of 9.2 months and median overall survival (OS,
across the entire study) of 9.1 months.
Selinexor recently received Fast Track
designation from the FDA for the patient population evaluated in
the SADAL study. Karyopharm plans to submit a New Drug Application
(NDA) to the FDA during the first half of 2019, with a request for
accelerated approval for oral single-agent selinexor as a new
treatment for patients with relapsed or refractory DLBCL.
Top-Line Phase 2b SADAL
Results
Based on the modified intention-to-treat
analysis from the first 115 of 127 patients (median of 2 prior
treatment regimens with a range 1-6), as adjudicated by an
independent central radiological committee, 34 patients responded
(11 patients with a CR and 23 patients with a PR) for an ORR of
29.6%. An additional 8 patients experienced stable disease (SD) for
a disease control rate of 36.5%. The median DOR across responding
patients was 9.2 months and responses tended to occur rapidly.
Patients with a CR had a median DOR of 23.0 months and patients
with a PR had a median DOR of 7.8 months. As of the data cutoff
date of November 15, 2018, 7 patients who achieved a CR remained on
treatment. In addition, 12 patients remain on treatment, but as of
November 15th, had not reached their first response assessment and
are not included in the top-line efficacy analyses.
Among the patients evaluated for safety as of
the data cutoff date, the most common treatment-related adverse
events (AEs) were gastrointestinal and constitutional symptoms,
along with cytopenias; most manageable with dose modifications
and/or supportive care. The most common non-hematologic AEs
were nausea (50.0%), fatigue (35.9%), and anorexia (32.0%) and
mostly Grade 1 and 2 events. As expected, the most common
Grade 3 and 4 AEs were thrombocytopenia (35.2%), neutropenia
(20.3%), and anemia (10.9%) and were generally not associated with
clinical sequelae. No significant major organ toxicities were
observed, and bleeding and infection rates were low.
The median OS was 9.1 months for all patients in
the study. As of the data cutoff date, median survival for
the patients with a CR or PR was 29.7 months. The median survival
for patients with best response of progressive disease or who were
not evaluable for response was 3.2 months.
Selinexor showed robust, single-agent activity
in patients with either GCB or non-GCB subtypes of DLBCL: of the 53
patients with the GCB-subtype, 18 responded (5 patients with a CR
and 13 patients with a PR) for an ORR of 34.0%. Of the 57 patients
with the non-GCB subtype, 12 responded (6 patients with a CR and 6
patients with a PR) for an ORR of 21.1%. In addition, there
were 5 patients enrolled whose subtype was unclassified and 4 of
these patients achieved a PR.
“The SADAL data presented at ASH this year
demonstrate that oral selinexor, when administered as a
single-agent, is clinically active and capable of producing durable
responses associated with prolonged overall survival,” said Marie
Maerevoet, MD, Institute Jules Bordet, “The 60mg twice weekly oral
dose continues to be well tolerated with a low incidence of Grade 3
or greater adverse events, which were often manageable with dose
modifications and supportive care. We are highly encouraged by the
results of this single agent study in patients with heavily
pretreated DLBCL who have limited available treatment options.”
Sharon Shacham, PhD, MBA, President and Chief
Scientific Officer of Karyopharm, said, “In addition to the
compelling efficacy and safety data observed with single agent oral
selinexor, we were especially pleased to see strong response rates
in patients with both the GCB and non-GCB subtypes. This is
especially important because the prognosis in patients with
refractory disease and the GCB-subtype is particularly poor.
We believe that if selinexor is ultimately approved for use
in patients with DLBCL, it will provide a meaningful therapeutic
option for patients battling refractory disease regardless of DLBCL
subtype. We look forward to submitting these data to the FDA during
the first half of 2019 as part of a New Drug Application, with a
request for accelerated approval.”
Details for the Poster Presentation at
ASH 2018:
Title: Single Agent Oral
Selinexor Demonstrates Deep and Durable Responses in
Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) in Both
GCB and Non-GCB Subtypes: The Phase 2b SADAL
StudyPresenter: Marie Maerevoet, Institute Jules
Bordet, Brussels, BelgiumAbstract Number/Publication
ID: 1677Session: 626. Aggressive Lymphoma
(Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin
Lymphomas)—Results from Prospective Clinical Trials: Poster
IDate and Time: Saturday, December 1, 2018;
6:15-8:15 PM PTLocation: San Diego Convention
Center, Hall GH
About Selinexor
Selinexor 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 2,800 patients have been treated with
selinexor. In April and September 2018, Karyopharm reported
positive data from the Phase 2b STORM study evaluating selinexor in
combination with low-dose dexamethasone in patients with
penta-refractory multiple myeloma. Selinexor has been granted
Orphan Drug Designation in multiple myeloma and Fast Track
designation for the patient population evaluated in the STORM
study. Karyopharm’s New Drug Application (NDA) has been accepted
for filing and granted Priority Review by the FDA, and oral
selinexor is currently under review by the FDA as a possible new
treatment for patients with penta-refractory multiple myeloma. The
Company also plans to submit a Marketing Authorization Application
(MAA) to the European Medicines Agency (EMA) in early 2019 with a
request for conditional approval. Selinexor is also being evaluated
in several other 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), as a potential
backbone therapy in combination with approved therapies (STOMP), in
diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an
investigator-sponsored study 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.
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 our expectations relating to submissions and to the
review and potential approval of selinexor by regulatory
authorities, including the anticipated timing of such submissions
and actions, and the potential availability of accelerated approval
pathways, the therapeutic potential of and potential clinical
development plans for Karyopharm's drug candidates, especially
selinexor, and the plans for commercialization. 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
regulators will agree that selinexor qualifies for accelerated
approval in the U.S. or conditional approval in the E.U. as a
result of the data from the STORM study in patients with
penta-refractory myeloma or the SADAL study in patients with
relapsed or refractory DLBCL 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 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 September 30, 2018, which was filed with
the Securities and Exchange Commission (SEC) on November 8, 2018,
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:Karyopharm
Therapeutics Inc.Ian KarpVice President, Investor and Public
Relations857-297-2241 | ikarp@karyopharm.com
Media:Argot PartnersDavid
Rosen212-600-1902 | david.rosen@argotpartners.com
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