Co-primary Endpoint Changed to Absolute Total
Symptom Score (Abs-TSS) from Total Symptom Score Improvement of ≥
50% (TSS50) Following Alignment with the FDA
Spleen Volume Response Rate ≥ 35% (SVR35)
Remains a Co-primary Endpoint
Promising Improvement in Abs-TSS and
SVR35 from Phase 1 Trial of Selinexor in Combination with
Ruxolitinib Adds Confidence in Phase 3 SENTRY Trial
Proactively Increasing Total Sample Size of
the SENTRY Trial to Approximately 350 Patients to Further Increase
the Statistical Powering; Expected Top-line Data Read-out Remains
in 2H 2025
Company to Host a Conference Call Today at
8:00 a.m. ET Featuring Drs. Raajit
Rampal and John Mascarenhas
NEWTON,
Mass., Oct. 31, 2024 /PRNewswire/ -- Karyopharm
Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical
company pioneering novel cancer therapies, today announced that,
following feedback from the U.S. Food and Drug Administration
(FDA), the Company will be replacing TSS50, one of the co-primary
endpoints in the Phase 3 SENTRY Trial (NCT04562389) with Abs-TSS.
Abs-TSS measures the average improvement in patient symptom scores
over 24 weeks relative to the patient's baseline symptom
score.
"There remains a tremendous unmet need in
myelofibrosis, as less than half of patients achieve SVR35 with
each of the approved JAK inhibitors and many patients eventually
stop responding to these treatments," said Dr. Raajit Rampal,
Director of the Center for Hematologic Malignancies and Director of
the Myeloproliferative Neoplasms Program at Memorial Sloan
Kettering Cancer Center. "The Phase 1 trial, which evaluates the
combination of selinexor and ruxolitinib, shows an approximate
doubling of SVR35 to nearly 80% compared to historical JAKi
monotherapy, and meaningful improvements in Abs-TSS with an average
18.5 point improvement at week 24 compared to baseline. I
believe these data are meaningful and impressive and provide a
strong rationale for the Phase 3 SENTRY trial."
Data from the Company's Phase 1 trial, evaluating
the combination of selinexor 60mg plus ruxolitinib in JAKi naïve
myelofibrosis patients, demonstrated that 79% of patients in the
intent to treat population (n=14) achieved SVR35 and an average
Abs-TSS improvement of 18.5 points in the efficacy evaluable
population (n=9), at week 24 relative to baseline. Acknowledging
the small sample size, these data are favorable to historical
ruxolitinib monotherapy data which indicates that less than half of
patients achieve SVR35 and an Abs-TSS improvement of 11 to 14
points1. The safety profile remains consistent and no
new safety signals have been identified.
"Our confidence in the success of our Phase 3
SENTRY trial increases based on the change in the co-primary
endpoint to Abs-TSS, the increased sample size and the data
previously presented from our Phase 1 trial evaluating selinexor
plus ruxolitinib in JAKi naïve myelofibrosis patients," said
Reshma Rangwala, MD, PhD, Chief
Medical Officer and Head of Research at Karyopharm. "Based upon
strong enrollment, we remain on track to report top-line results in
the second half of 2025."
"Improving symptomatic burden for patients with
myelofibrosis is an important goal in therapy, directly linking to
decreases in morbidity and likely mortality", said Dr. Ruben Mesa, President of Atrium Health
Levine Cancer and Charles L. Spurr, MD Professor of Internal
Medicine, Wake Forest University School
of Medicine. "I am very encouraged by the benefits reported in
Karyopharm's Phase 1 trial of selinexor combined with standard of
care ruxolitinib, especially regarding disease associated symptoms.
Additionally, I am grateful that the ongoing Phase 3 trial will use
Abs-TSS as a co-primary endpoint, which may better represent the
cumulative benefit patients experience on symptom burden."
Abs-TSS is an accepted measure that has been used
in other Phase 3 clinical trials in myelofibrosis to evaluate the
benefit/risk of an add-on treatment, such as selinexor, to the
current standard of care. The change to Abs-TSS is strongly
supported by key leading investigators and patient advocacy
organizations, which generally view improvement in Abs-TSS from
baseline as a more accurate assessment of symptom improvement in
head-to-head clinical trials, such as SENTRY.
"We are vocal advocates for evolving
myelofibrosis clinical trial endpoints. Growing data that support a
newer outcome measure like Abs-TSS that is also meaningful to
patients is very encouraging," said Kapila
Viges, Chief Executive Officer, MPN Research Foundation.
"Efforts to develop effective treatments and combination therapies
with patients' goals for care in mind are important. For
myelofibrosis patients and their families, options matter."
Company Conference Call Information
Karyopharm will host a conference call with
management and Drs. Raajit Rampal and John Mascarenhas to
discuss the Phase 3 SENTRY trial today, October 31, 2024, at 8:00 a.m. Eastern Time.
To access the conference call, please dial (800) 836-8184 (local)
or (646) 357-8785 (international) at least 10 minutes prior to the
start time and ask to be joined into the Karyopharm Therapeutics
call. A live audio webcast, along with accompanying slides, will be
available under "Events & Presentations" in the Investor
section of the Company's website,
http://investors.karyopharm.com/events-presentations. An archived
webcast will be available on the Company's website approximately
two hours after the event.
References
1Phase 3 MANIFEST trial. Rampal R, et
al. ASH 2023. Oral 628; Phase 3 TRANSFORM-1 trial Pemmaraju N, et
al. ASH 2023 abstract 620.
About the Phase 3 SENTRY Trial
SENTRY (NCT04562389) is a pivotal, Phase 3
clinical trial evaluating a once-weekly dose of 60mg of selinexor
in combination with twice-daily ruxolitinib versus placebo plus
ruxolitinib in JAKi naïve patients with platelet counts >100 x
109/L. Karyopharm intends to enroll
approximately 350 JAKi naïve patients with myelofibrosis in this
Phase 3 trial; patients are randomized 2-to-1 to the selinexor arm.
The co-primary endpoints will be spleen volume response rate ≥ 35%
(SVR35) at week 24 and the change in absolute total symptom score
(Abs-TSS) over 24 weeks relative to baseline.
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 whose dedication to
pioneering novel cancer therapies is fueled by a belief in the
extraordinary strength and courage of patients with cancer. Since
its founding, Karyopharm has been an industry leader in oral
compounds that address nuclear export dysregulation, a fundamental
mechanism of oncogenesis. Karyopharm's lead 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. It has also
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 indications in multiple high unmet need cancers,
including in multiple myeloma, endometrial cancer, myelofibrosis,
and diffuse large B-cell lymphoma (DLBCL). For more information
about our people, science and pipeline, please visit
www.karyopharm.com, and follow us on LinkedIn and on X at
@Karyopharm.
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 with respect to the clinical
development plans and potential regulatory submissions of selinexor
for the treatment of myelofibrosis. 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, 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 trials, including subsequent analysis of
existing data and new data received from ongoing and future trials;
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
trials; 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 June 30, 2024, which was filed with the Securities and
Exchange Commission (SEC) on August 6, 2024, 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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