Biomarker Data from Phase 1 Study
of Selinexor in Combination with Ruxolitinib in
Treatment-Naïve Myelofibrosis (MF) Suggestive of Disease
Modification
Data Reinforce the Potential for Selinexor in
Combination with Ruxolitinib to Become a Novel, First-Line
Treatment for JAKi-Naïve Patients with MF
NEWTON,
Mass., Dec. 10, 2023 /PRNewswire/ -- Karyopharm
Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical
company pioneering novel cancer therapies, today announced
long-term follow up of treatment-naïve patients with myelofibrosis
(MF) who participated in the Phase 1 portion of its study
evaluating once-weekly selinexor in combination with ruxolitinib
(NCT04562389). The data, featured in an oral presentation at the
65th American Society of Hematology Annual Meeting and Exposition
(ASH 2023), show patients treated with 60mg selinexor, and who
achieved ≥35% reduction in spleen volume (SVR35) at week 24,
continued to remain in radiographic response. In addition, all
patients who achieved TSS50 at Week 24 remained in response as of
the data cut-off.
The data included in the oral presentation for ASH 2023 were
based on the Phase 1 portion of the Phase 1/3 study evaluating the
safety and efficacy of once-weekly selinexor in combination with
ruxolitinib in patients with treatment-naïve MF (NCT04562389). As
of August 1, 2023, 24 patients had
been assigned to either selinexor 40mg (N= 10) or 60mg (N=14), in
combination with ruxolitinib. The maximum duration of follow-up was
78 weeks with a median duration of 32 weeks for SVR35 durability,
and a maximum duration of follow-up was 64 weeks with a median
duration of 51 weeks for TSS50 durability.
An exploratory biomarker analysis showed a reduction of variant
allele frequency (VAF) at week 24 for all three MF driver genes
(CALR, MPL, and JAK2) and rapid and sustained reduction of
pro-inflammatory cytokine production. Early cytokine reduction at
Week 4 was associated with spleen volume reduction (SVR) at Week 24
and was sustained until the end of treatment. The clinical efficacy
associated with biomarkers impacting MF biological hallmarks may
suggest disease modification.
"The growing body of data from this study suggests that
selinexor in combination with ruxolitinib may provide spleen
reduction, symptom improvement, long-term durability and disease
modification, expanding the benefit this combination may provide to
patients with treatment-naïve myelofibrosis, " said Reshma Rangwala, MD, PhD, Chief Medical Officer
of Karyopharm. "We're excited about the potential to change
treatment paradigms for these patients – and expand the number of
patients who benefit from first-line therapy."
The safety profile was consistent with previous data cuts with
no new safety signals observed as of Aug
1st.
"The current standard of care is not associated with consistent
molecular or pathologic responses," said Dr. Sri Tantravahi, University
of Utah. "The long-term findings are very exciting as they
underscore the potential for durable, clinically relevant responses
and modification of disease course. The wait for new options has
been long and difficult for the myelofibrosis community, and we
welcome this important research to help advance the understanding
of XPO1 and JAK inhibitor combinations as a meaningful treatment
option for patients."
"We are encouraged by the attention MPNs
(Myeloproliferative Neoplasms) are getting in recent years from
companies like Karyopharm," said Kapila
Viges, Chief Executive Officer of MPN Research Foundation.
"With patients waiting for more answers to these chronic yet
serious blood cancers, we look forward to the data readouts at ASH
this year. Efforts to develop better therapies and now combinations
of therapies bring hope to the myelofibrosis community and open the
potential for more options in the treatment paradigm. For patients,
options matter."
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 syndromes 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 multiple myeloma,
myelofibrosis, diffuse large B-cell lymphoma, solid tumors and
other diseases; and expectations related to the clinical
development plans 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
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; the
direct or indirect impact of the COVID-19 pandemic or any future
pandemic on Karyopharm's business, results of operations and
financial condition; 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 September 30, 2023, which was filed with the
Securities and Exchange Commission (SEC) on November 2, 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.
References:
1 For SVR 35: Events defined as less than or
equal to 35% spleen volume reduction from baseline and more than
25% increase in spleen volume from Nadir, assessed
radiographically. For TSS50: Events defined as a total symptom
score that is equal to or exceeds the baseline value. As of
August 1, 2023 data cut off.
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