Phase 3 Study is Supported by Previously
Presented Phase 1 Study Results, Including a 78.6% SVR35 and
58.3% TSS50 in Intent to Treat Patients at Week 24 at the 60mg
Dose
NEWTON,
Mass., June 28, 2023 /PRNewswire/ -- Karyopharm
Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical
company pioneering novel cancer therapies, today announced the
initiation of a pivotal Phase 3 clinical trial (XPORT-MF-034)
(NCT04562389) to assess the efficacy and safety of once-weekly
selinexor 60mg in combination with ruxolitinib in JAKi-naïve
patients with myelofibrosis.
The randomized, double-blind, placebo-controlled study is
expected to enroll 306 JAKi-naive patients with intermediate or
high-risk myelofibrosis. Patients will be randomized 2:1 to
ruxolitinib plus selinexor 60mg or ruxolitinib plus placebo in
28-day cycles. Ruxolitinib dose will be determined by the
investigators based on the patients' baseline platelet count per
the drug's prescribing information. The co-primary endpoints of the
study are spleen volume response rate of ≥ 35% (SVR35) and symptom
improvement of ≥ 50% (TSS50) at week 24, with a key secondary
endpoint of anemia response at week 24.
"Selinexor and ruxolitinib appear to work synergistically,
resulting in meaningful improvements in spleen response and total
symptom score for patients with myelofibrosis," said Reshma Rangwala, MD, PhD, Chief Medical Officer
of Karyopharm. "We believe that an opportunity exists to expand
upon the initial response, depth, and duration of JAK inhibitors to
ultimately improve patient outcomes. This combination has the
potential to become a cornerstone treatment in front-line
myelofibrosis and we are excited to start this pivotal trial to
deliver on our goal of bringing forward an innovative new approach
for the treatment of myelofibrosis that can benefit MF
patients."
"The substantial degree of spleen volume reduction observed
across all subgroups with selinexor 60mg in combination with
ruxolitinib is very encouraging. There is a significant unmet need
in the treatment of patients with myelofibrosis, and these data
demonstrate that the addition of XPO1 inhibition with selinexor
with standard-of-care ruxolitinib has the potential to
significantly improve outcomes for first-line myelofibrosis
patients," said Dr. John
Mascarenhas, Professor of Medicine at the Icahn School of
Medicine at Mount Sinai and Director of the Center of Excellence
for Blood Cancers and Myeloid Disorders. "As the principal
investigator for the Phase 3 study, I look forward to defining a
potential new standard of care for Jak naïve MF patients."
Updated data from the Phase 1 study recently presented at
American Association for Cancer Research (AACR) Annual Meeting
2023, American Society of Clinical Oncology (ASCO) 2023 and
European Hematology Association (EHA) 2023 showed rapid, deep and
sustained spleen responses and robust symptom improvement in
patients treated with selinexor 60mg in combination with
ruxolitinib as of the April 10, 2023
data cut-off date:
- At week 24, 91.7% (11/12) of efficacy evaluable patients
demonstrated SVR35 and 77.8% (7/9) achieved TSS50. The intent to
treat population achieved a 78.6% (11/14) SVR35 and 58.3% (7/12)
TSS50 respectively.
- SVR35 responses were observed in 100% (12/12) of evaluable
patients at any time and rates were consistent regardless of
subgroups, including males and patients treated with low dose
ruxolitinib.
- Improvement in major spleen and cytokine-related symptoms were
observed across all Myelofibrosis Symptom Assessment Form
domains.
- Selinexor was generally well tolerated with a manageable side
effect profile, allowing most patients to remain on therapy, up to
74 weeks, as of the data cut-off date. The most common treatment
emergent adverse events, regardless of grade, experienced with the
60mg selinexor dose, in combination with ruxolitinib were nausea
(78.6%), anemia (64.3%), thrombocytopenia (64.3%) and fatigue
(57.1%), and most common treatment emergent grade ≥3 adverse events
experienced with the 60mg selinexor dose, in combination with
ruxolitinib were anemia (42.9%), thrombocytopenia (28.6%) and back
pain (14.3%)
- 75% of nausea events were grade 1, were mostly transient and
did not lead to treatment-related discontinuations. Nausea rates
and grades were reduced for patients who received prophylactic
antiemetics. Meaningful weight gain was observed at week 24 despite
the incidence of nausea and vomiting.
Further information about the Phase 3 study can be found at
www.clinicaltrials.gov.
Karyopharm expects to present top-line data readout from this
study in 2025. The company plans to expand its clinical development
program in myelofibrosis by investigating selinexor in other
front-line opportunities, such as novel combinations, to benefit
the greatest number of myelofibrosis patients.
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and
the first of Karyopharm's Selective Inhibitor of Nuclear Export
(SINE) compounds to be approved for the treatment of cancer. XPOVIO
functions by selectively binding to and inhibiting the nuclear
export protein XPO1. XPOVIO is approved in the U.S. and marketed by
Karyopharm in multiple oncology indications, including: (i) in
combination with Velcade® (bortezomib) and dexamethasone (XVd) in
patients with multiple myeloma after at least one prior therapy;
(ii) in combination with dexamethasone in patients with heavily
pre-treated multiple myeloma; and (iii) in patients with diffuse
large B-cell lymphoma (DLBCL), including DLBCL arising from
follicular lymphoma, after at least two lines of systemic therapy.
XPOVIO (also known as NEXPOVIO® in certain countries) has received
regulatory approvals in various indications in a growing number of
ex-U.S. territories and countries, including but not limited to the
European Union, the United
Kingdom, China,
South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by
Karyopharm's partners, Antengene, Menarini, Neopharm and FORUS, in
China, South Korea, Singapore, Australia, Hong
Kong, Germany, Austria, Israel and Canada.
Please refer to the local Prescribing Information for full
details.
Selinexor is also being investigated in several other mid- and
late-stage clinical trials across multiple high unmet need cancer
indications, including in endometrial cancer and myelofibrosis.
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
SELECT IMPORTANT SAFETY INFORMATION
Warnings and Precautions
- Thrombocytopenia: Monitor platelet counts throughout treatment.
Manage with dose interruption and/or reduction and supportive
care.
- Neutropenia: Monitor neutrophil counts throughout treatment.
Manage with dose interruption and/or reduction and granulocyte
colony–stimulating factors.
- Gastrointestinal Toxicity: Nausea, vomiting, diarrhea,
anorexia, and weight loss may occur. Provide antiemetic
prophylaxis. Manage with dose interruption and/or reduction,
antiemetics, and supportive care.
- Hyponatremia: Monitor serum sodium levels throughout treatment.
Correct for concurrent hyperglycemia and high serum paraprotein
levels. Manage with dose interruption, reduction, or
discontinuation, and supportive care.
- Serious Infection: Monitor for infection and treat
promptly.
- Neurological Toxicity: Advise patients to refrain from driving
and engaging in hazardous occupations or activities until
neurological toxicity resolves. Optimize hydration status and
concomitant medications to avoid dizziness or mental status
changes.
- Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of
reproductive potential and males with a female partner of
reproductive potential, of the potential risk to a fetus and use of
effective contraception.
- Cataract: Cataracts may develop or progress. Treatment of
cataracts usually requires surgical removal of the cataract.
Adverse Reactions
- The most common adverse reactions (≥20%) in patients with
multiple myeloma who receive XVd are fatigue, nausea, decreased
appetite, diarrhea, peripheral neuropathy, upper respiratory tract
infection, decreased weight, cataract and vomiting. Grade 3–4
laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia,
hypophosphatemia, anemia, hyponatremia and neutropenia. In the
BOSTON trial, fatal adverse
reactions occurred in 6% of patients within 30 days of last
treatment. Serious adverse reactions occurred in 52% of patients.
Treatment discontinuation rate due to adverse reactions was
19%.
- The most common adverse reactions (≥20%) in patients with
multiple myeloma who receive Xd are thrombocytopenia, fatigue,
nausea, anemia, decreased appetite, decreased weight, diarrhea,
vomiting, hyponatremia, neutropenia, leukopenia, constipation,
dyspnea and upper respiratory tract infection. In the STORM trial,
fatal adverse reactions occurred in 9% of patients. Serious adverse
reactions occurred in 58% of patients. Treatment discontinuation
rate due to adverse reactions was 27%.
- The most common adverse reactions (incidence ≥20%) in patients
with DLBCL, excluding laboratory abnormalities, are fatigue,
nausea, diarrhea, appetite decrease, weight decrease, constipation,
vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%)
are thrombocytopenia, lymphopenia, neutropenia, anemia, and
hyponatremia. In the SADAL trial, fatal adverse reactions occurred
in 3.7% of patients within 30 days, and 5% of patients within 60
days of last treatment; the most frequent fatal adverse reactions
was infection (4.5% of patients). Serious adverse reactions
occurred in 46% of patients; the most frequent serious adverse
reaction was infection (21% of patients). Discontinuation due to
adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to
breastfeed.
For additional product information, including full prescribing
information,
please visit www.XPOVIO.com.
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.
About Karyopharm Therapeutics
Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a
commercial-stage pharmaceutical company pioneering novel cancer
therapies. Since its founding, Karyopharm has been an industry
leader in oral Selective Inhibitor of Nuclear Export (SINE)
compound technology, which was developed to address a fundamental
mechanism of oncogenesis: nuclear export dysregulation.
Karyopharm's lead SINE compound and first-in-class, oral exportin 1
(XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and
marketed by the Company in three oncology indications and has
received regulatory approvals in various indications in a growing
number of ex-U.S. territories and countries, including Europe and the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline
targeting multiple high unmet need cancer indications, including in
multiple myeloma, endometrial cancer, myelodysplastic neoplasms and
myelofibrosis. For more information about our people, science and
pipeline, please visit www.karyopharm.com, and follow us on Twitter
at @Karyopharm and LinkedIn.
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
ability of selinexor to treat patients with myelofibrosis; and
expectations related to the clinical development of selinexor and
potential regulatory submissions of 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 or that any of
Karyopharm's drug candidates, including selinexor and eltanexor,
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 obtain and 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 enroll patients in its clinical trials;
unplanned cash requirements and expenditures; development or
regulatory approval of drug candidates by Karyopharm's competitors
for products or product candidates in which Karyopharm is currently
commercializing or developing; and Karyopharm's ability to obtain,
maintain and enforce patent and other intellectual property
protection for any of its products or product candidates. These and
other risks are described under the caption "Risk Factors" in
Karyopharm's Quarterly Report on Form 10-Q for the quarter ended
March 31, 2023, which was filed with
the Securities and Exchange Commission (SEC) on May 4, 2023, 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.
XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm
Therapeutics Inc. Any other trademarks referred to in this release
are the property of their respective owners.
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SOURCE Karyopharm Therapeutics Inc.