Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage
pharmaceutical company, today reported positive top-line results
from its Phase 2b STORM study evaluating the activity of selinexor
(KPT-330) in multiple myeloma (MM). Selinexor, the Company’s lead,
novel, oral Selective Inhibitor of Nuclear Export / SINE™ compound,
is being developed for the treatment of a variety of malignancies,
including MM. Karyopharm also provided an overview of the planned
development path for selinexor in MM.
The Phase 2b STORM study is a single-arm
clinical trial evaluating selinexor in combination with low-dose
dexamethasone in heavily pretreated MM patients, meaning patients
with quad-refractory disease or penta-refractory disease. Patients
with quad-refractory disease have previously received two
proteasome inhibitors (PIs) (bortezomib (Velcade®) and carfilzomib
(Kyprolis®)) and two immunomodulatory agents (IMiDs) (lenalidomide
(Revlimid®) and pomalidomide (Pomalyst®)), and their disease is
refractory to at least one PI, at least one IMiD, and has
progressed following their most recent therapy. Patients with
penta-refractory myeloma have quad-refractory disease that is also
refractory to an anti-CD38 monoclonal antibody, such as daratumumab
(Darzalex™) or isatuximab.
Among the 78 evaluable patients (median seven
prior treatment regimens), the overall response rate (ORR) was
20.5% based on Independent Review Committee adjudication, including
very good partial responses (VGPR) and partial responses (PR).
Among the 48 patients in the quad-refractory group, the ORR
was 20.8%. For comparison, in a similar quad-refractory patient
population, Darzalex had an ORR of 21% and isatuximab had an ORR of
20%. Among the 30 patients in the penta-refractory group, the
ORR was 20.0%. Several patients remain on study, including those
with VGPRs, PRs and minor responses. To the Company’s knowledge, no
agent has previously shown activity in this penta-refractory
population. The side effect profile for selinexor was consistent
with previous trials, and no new safety signals were identified.
Additional data will be presented later this year.
Keith Stewart, MB. ChB., Anna Maria and Vasek
Polack Professor of Cancer Research at the Mayo Clinic and lead
investigator of the STORM study, said, “Although treatment of
multiple myeloma has improved dramatically, eventually many
patients will develop refractory disease, no longer responding to
any of the immunomodulatory agents and proteasome inhibitors
commonly used (quad-refractory). These patients will also
eventually progress on anti-CD38 monoclonal antibodies, which we
refer to as penta-refractory disease. These are clearly the
patients with the highest unmet need, as they have no remaining
viable treatment options. The STORM data are compelling because
they demonstrate that oral selinexor achieves a 20.8% response rate
in the quad-refractory group, similar to recently reported
intravenous anti-CD38 therapy results in the same patient
population. Selinexor also achieves an equally notable 20.0%
response rate in the penta-refractory group, with the significant
advantage of oral administration. We are currently unaware of
any other therapy, oral or intravenous, reporting such activity in
these difficult-to-treat patients who have exhausted all available
therapies.”
In addition to the STORM study, Karyopharm
initiated the Phase 1b/2 STOMP (Selinexor and
Backbone Treatments of Multiple
Myeloma Patients) study to
evaluate selinexor in combination with existing therapies across
the broader population in MM. In the arm evaluating the combination
of selinexor, bortezomib and dexamethasone, dose escalation has
been completed and the recommended dose has been determined,
providing a basis for the randomized Phase 3 “BOSTON” study
described below.
Sagar Lonial, MD, Professor and Chair,
Department of Hematology and Medical Oncology, Emory University
School of Medicine and Chief Medical Officer, Winship Cancer
Institute of Emory University, commented, “Myeloma continues to be
an incurable blood cancer in most patients and our main goal in
treating refractory disease is to induce responses and maintain
them as long as possible. In addition to these new data with oral
selinexor and low-dose dexamethasone, the emerging clinical data
from selinexor in combination with bortezomib, including in
proteasome-inhibitor refractory disease, suggests a synergistic
effect and favorable safety profile. These data are quite exciting
and will form the basis for future studies.”
Selinexor: Multiple Myeloma Clinical
Development Plans and Timelines
Based on these positive top-line STORM data and
existing unmet medical need, Karyopharm plans to implement the
following clinical development initiatives focusing on obtaining
regulatory approval of selinexor in MM:
- Karyopharm is expanding the STORM study to include
approximately 120 additional patients with penta-refractory MM. To
the Company’s knowledge, this will be the largest study ever
undertaken in this patient population. Assuming a positive outcome
and remaining unmet medical need, Karyopharm intends to use the
data from the expanded STORM study to support a request that the
FDA consider granting accelerated approval for selinexor in MM. The
Company anticipates reporting top-line data from the expanded
cohort in early 2018.
- The FDA instituted its Accelerated Approval Program to allow
for expedited approval of drugs that treat serious conditions and
that fill an unmet medical need based on a surrogate endpoint or an
intermediate clinical endpoint thought to predict clinical benefit,
like ORR. Accelerated approval is available only for drugs that
provide a meaningful therapeutic benefit over existing treatments
at the time of consideration of the application for accelerated
approval, which the FDA has reiterated in its feedback to the
Company. Particularly in disease areas with multiple available and
potential new therapies, such as MM, accelerated approval carries a
high regulatory threshold. Drugs approved under the Accelerated
Approval Program are also typically required to be studied in
randomized confirmatory trials on a post-approval basis to confirm
clinical benefit. Given the number of approved and
experimental therapies in development to treat MM, and consistent
with its standard guidance, the FDA has recommended that the
Company conduct a randomized study geared towards full approval,
which the Company is planning with the BOSTON study discussed
below. In addition, to the Company’s knowledge, no other
studies are currently being conducted in the penta-refractory
patient population and no agents have shown activity in these
patients. In light of this unmet medical need, the Company believes
that positive data in this patient population could support
accelerated approval. The FDA has stated to the Company that
other therapies in MM may receive full approval prior to the
potential action date on any accelerated approval request for
selinexor that the Company may submit, which may prevent
accelerated approval for selinexor if the FDA deems that such
therapies constitute earlier lines of therapy in MM that were not
administered to patients in the STORM study. Also, while the
FDA has previously indicated its preference for studies that
isolate the effects of individual drugs, steroids like
dexamethasone are part of nearly every myeloma treatment regimen,
and low-dose dexamethasone is not a single-agent treatment for MM.
Other available therapies for MM, such as pomalidomide (Pomalyst®),
have received accelerated approval based on studies that were
conducted in combination with dexamethasone or a similar steroid.
Based on these factors, the Company believes that the STORM study
design and the planned expansion in the penta-refractory patient
group present an opportunity for the Company to request that the
FDA grant accelerated approval if data from the expansion confirm
the data presented today.
- The Company also plans to initiate a pivotal randomized Phase 3
study, known as the BOSTON (Bortezomib,
Selinexor and
dexamethasone) study, which will
evaluate selinexor in combination with bortezomib (Velcade®) and
low-dose dexamethasone (SVd) compared to bortezomib and low-dose
dexamethasone (Vd) in patients with MM who have had one to three
prior lines of therapy. Based on data from the Phase 1b
portion of the STOMP study, which was most recently presented at
the 2016 European Hematology Association Annual Meeting, the
Company has identified the combination dose to be used in the
BOSTON study. Karyopharm expects that the study will enroll
approximately 360 patients. The Company intends to seek
additional FDA input on the protocol for the BOSTON study prior to
commencing the trial in early 2017.
- Based in part on its plans to conduct the pivotal randomized
BOSTON study to support full regulatory approval of selinexor for
patients with previously-treated MM and the Company’s planned
expansion of STORM to support potential accelerated approval,
Karyopharm will not pursue the SCORE study at this time. The
SCORE study was designed to assess the combination of selinexor
with carfilzomib (Kyprolis®) and low-dose dexamethasone. The
ongoing Phase 1/2 investigator sponsored study evaluating selinexor
in combination with carfilzomib and dexamethasone in refractory MM,
including carfilzomib-refractory MM, continues to enroll patients,
and updated data from this study is expected to be presented later
this year.
“Our updated clinical development plan for
selinexor in myeloma reflects the strong foundation of clinical
data from both the STORM and STOMP studies,” said Michael G.
Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. Dr.
Kauffman was instrumental in the clinical development and
regulatory approvals of Velcade® and Kyprolis® in MM. “We believe
this development plan provides a path to potential FDA and EMA
filings for oral selinexor in MM, with the potential to support
accelerated or conditional approval if the FDA or EMA,
respectively, agree. We look forward to sharing the additional data
from both STORM and STOMP later this year. We believe selinexor has
the potential to be a much-needed oral treatment option for
patients suffering with this incurable disease.”
More About the Phase 2b STORM
Study
The Phase 2b STORM (Selinexor
Treatment of
Refractory Myeloma) (NCT02336815)
study is a multi-center, single-arm clinical trial evaluating
selinexor in combination with low-dose dexamethasone in patients
with heavily-pretreated multiple myeloma (MM), which the Company
refers to as having at least quad-refractory MM. These are
patients who have received bortezomib (Velcade®) and carfilzomib
(Kyprolis®), each of which is a proteasome inhibitor (PI), and
lenalidomide (Revlimid®) and pomalidomide (Pomalyst®), each of
which is an immunomodulatory agent (IMiD), and whose disease is
refractory to at least one PI, at least one IMiD, and is refractory
to their most recent therapy. Prior treatment regimens must
have also included an alkylating agent and a glucocorticoid.
In the original version of the protocol, at least 25% of patients
in this study must have had MM that is also refractory to an
anti-CD38 monoclonal antibody, such as daratumumab (DarzalexTM),
which the Company refers to as having penta-refractory MM. Of
the 79 patients enrolled in the first cohort, 78 had measurable
disease at baseline, with 48 (62%) patients classified as having
quad-refractory and 30 (38%) patients classified as having
penta-refractory MM.
The primary endpoint of the STORM study is
overall response rate (ORR). The original trial had several
secondary endpoints, including ORR in patients whose disease is
relapsed/refractory to an anti-CD38 monoclonal antibody, duration
of response (DOR) and clinical benefit rate (CBR). Karyopharm
is now expanding the STORM study to include additional sites in the
United States and Europe to enroll approximately 120 additional
patients with penta-refractory MM to further evaluate the safety
and efficacy of selinexor as a basis for potential regulatory
submission requesting accelerated (FDA) or conditional (EMA)
approval, based on ORR.
More About the Phase 1b/2 STOMP
Study
The Phase 1b/2 STOMP (NCT02343042) study is a
multi-arm clinical trial evaluating selinexor and low-dose
dexamethasone in combination with backbone therapies bortezomib
(Velcade®), pomalidomide (Pomalyst®) or lenalidomide (Revlimid®) in
patients with heavily pretreated relapsed/refractory MM. Each
combination is evaluated on a separate arm of the STOMP study and,
within each combination, each of two treatment cohorts will receive
either once weekly or twice weekly dosing of selinexor.
Data from the STOMP study was initially reported
at the European Hematology Association 2016 annual meeting.
As of June 8, 2016, of the 16 patients treated in the SVd
combination arm, all of whom are evaluable, 11 responded (1 patient
with a complete response (CR), 3 with VGPRs and 7 with PRs for an
ORR of 69%). An additional three patients achieved a minor
response (MR), for a CBR of 88%. Several of the patients on
this selinexor, Velcade and low-dose dexamethasone (SVd)
combination arm had high-risk haplotypes, including deletion of
chromosome 17p, and 10 of the 16 evaluable patients had MM
previously refractory to a proteasome inhibitor. Seven of
these 10 patients responded (1 CR, 1 VGPR, and 5 PRs) for an ORR of
70%. An additional patient achieved an MR for a CBR of 80% in
this subgroup. Overall, side effects reported in the SVd arm
were similar to, or less severe than, those observed with
single-agent selinexor. Karyopharm plans to submit updated
data from the STOMP study for presentation at a medical conference
later this year. The Company is also planning to add two additional
arms to the STOMP study – one to evaluate selinexor in combination
with daratumumab (Darzalex™) and the other to evaluate selinexor in
combination with Pomalyst, Velcade and low-dose dexamethasone.
Conference Call Information
Karyopharm will host a conference call today,
Tuesday, September 6, 2016, at 8:30 a.m. Eastern Time, to discuss
the top-line Phase 2b STORM results and the planned development
path for selinexor in multiple myeloma. To access the
conference call, please dial (855) 437-4406 (US) or (484) 756-4292
(international) at least five minutes prior to the start time and
refer to conference ID: 74213103. Accompanying slides will be
available under "Events & Presentations" in the "Investor"
section of Karyopharm's website, http://www.karyopharm.com,
where an audio recording of the call will be available
approximately two hours after the event.
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. Over 1,600 patients have been treated
with selinexor in company- and investigator-sponsored Phase 1 and
Phase 2 clinical trials in advanced hematologic malignancies and
solid tumors. Selinexor is currently being evaluated in several
mid- and later-stage clinical trials, including a Phase 2b
single-arm trial of selinexor and low-dose dexamethasone in
multiple myeloma (STORM), a Phase 1b/2 trial in combination with
backbone therapies in multiple myeloma (STOMP), a Phase 2 trial in
older patients with acute myeloid leukemia (SOPRA), a Phase 2b
trial in diffuse large B-cell lymphoma (SADAL), and a Phase 2/3
trial in 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. The latest
clinical trial information for selinexor is available
at www.clinicaltrials.gov.
About Multiple Myeloma
Multiple myeloma (MM) is form of blood cancer that develops in
the bone marrow. In multiple myeloma, normal plasma cells transform
into malignant myeloma cells and produce large quantities of an
abnormal immunoglobulin called monoclonal protein or M protein. The
monoclonal protein produced by myeloma cells interferes with normal
blood cell production. In addition, the levels of functional
immunoglobulins are depressed in individuals with multiple myeloma.
Although the process is not completely understood, it appears that
the functional immunoglobulins made by existing, healthy plasma
cells breaks down more quickly in patients with multiple myeloma
than in healthy individuals. MM is the second most commonly
diagnosed blood cancer after Non-Hodgkin’s Lymphoma (NHL).
According to SEER data from the National Cancer Institute, in the
United States in 2016 approximately 30,000 new cases of MM will be
diagnosed, and approximately 12,500 patients will die from the
disease. Approximately 100,000 people in the United States
were living with MM in 2013. According to GlobalData, the 2015 MM
market was valued at approximately $11 billion and the size of the
myeloma market is projected to increase to over $22 billion by
2023.
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 the
timing of initiation of certain trials and of the 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 the Company'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, 2016,
which was filed with the Securities and Exchange Commission (SEC)
on August 4, 2016, 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 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 LimitedRevlimid® and Pomalyst® are
registered trademarks of Celgene CorporationKyprolis® is a
registered trademark of Onyx Pharmaceuticals, Inc.DarzalexTM is a
trademark of Janssen Biotech, Inc.
Contact:
Justin Renz
(617) 658-0574
jrenz@karyopharm.com
Gina Nugent
(617) 460-3579
nugentcomm@aol.com
Karyopharm Therapeutics (NASDAQ:KPTI)
Historical Stock Chart
From Feb 2024 to Mar 2024
Karyopharm Therapeutics (NASDAQ:KPTI)
Historical Stock Chart
From Mar 2023 to Mar 2024