– Accelerating Innovation and Growth Strategy
with Top-Line Data Readouts Expected in 2H 2024 and 2025 from Three
Pivotal Phase 3 Studies Evaluating Selinexor in Multiple Myeloma,
Endometrial Cancer and Myelofibrosis –
– Preliminary Unaudited Full Year 2023 Total
Revenue and U.S. XPOVIO® (selinexor) Net Product Revenue
Expected to be Approximately $146
Million and $112 Million,
Respectively, Meeting Company's Guidance –
– Potential for Selinexor to be a Novel
Maintenance Treatment for Patients with TP53 Wild-Type Endometrial
Cancer Further Strengthened with Long-Term Exploratory Subgroup
Analyses from SIENDO Study; Recruitment Ongoing in the Company's
Pivotal Phase 3 Study; Further Updates Planned to be Presented in
2024 –
– Opportunity to Define a New Myelofibrosis
Treatment Paradigm Based on the Encouraging Data Presented from the
Phase 1 Study of Selinexor in Combination with Ruxolitinib in
Patients with Treatment-Naïve Myelofibrosis; Recruitment Ongoing in
the Company's Pivotal Phase 3 Study; Further Updates Planned to be
Presented in 2024 –
– Expect Cash Runway into Late 2025 Supporting
Company Through Multiple Potentially Value Generating Milestones
–
NEWTON,
Mass., Jan. 8, 2024 /PRNewswire/ -- Karyopharm
Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical
company pioneering novel cancer therapies, today announced
preliminary unaudited fourth quarter and full year 2023 total
revenue and U.S. XPOVIO net product revenue estimates and outlined
its 2023 achievements and 2024 objectives.
"2023 was a year focused on accelerating our prioritized
late-stage pipeline with updated data readouts from our studies in
endometrial cancer and myelofibrosis, strengthening our potential
to significantly improve outcomes for patients. We focused our
resources and delivered on our revenue guidance as we continued to
expand use of selinexor amidst a highly competitive multiple
myeloma landscape. In 2024, we will continue to concentrate our
investments to rapidly advance our pipeline and strengthen our
foundation in multiple myeloma and deliver value for patients and
our shareholders with multiple value driving catalysts expected
throughout 2024," said Richard
Paulson, President and Chief Executive Officer of
Karyopharm.
Key Program Highlights in 2023
Selinexor in Multiple Myeloma (MM)
- Total demand for XPOVIO grew in the community setting, which
accounted for approximately two-thirds of XPOVIO net product
revenue; in the academic setting, demand for XPOVIO was adversely
impacted by increased competitive pressures in the later lines.
- XPOVIO net product revenue was adversely impacted
year-over-year by increased utilization of the KaryForward Patient
Assistance Program (PAP), due to multiple myeloma foundation
closures1, contributing to ~10% of total demand in 2023
as compared to ~5% in 2022, leading to ~$6
million impact. Additionally, increased competition and
higher gross-to-net, driven by increased 340B discounts and Medicaid rebates during the
year, adversely impacted XPOVIO net product revenue.
- XPOVIO continued its strategic shift to earlier lines, with
patient mix approaching 70% in the second to fourth lines versus
55% in 20222, contributing to an increase in duration of
therapy.
- The National Comprehensive Cancer Network® (NCCN)
Clinical Practice Guidelines elevated XPOVIO in combination with
bortezomib (Velcade®) and dexamethasone (XVd) to a
preferred and category 1 regimen for lenalidomide-refractory
patients with relapsed or refractory multiple myeloma who have
received one-to-three prior lines of therapy in the September 2023 Clinical Practice Guidelines in
Oncology.
- Clinical trial collaboration agreement executed with Bristol
Myers Squibb (BMS) to evaluate selinexor in combination with BMS'
proprietary investigational cereblon E3 ligase modulator (CELMoD™)
agent mezigdomide in patients with relapsed/refractory multiple
myeloma progressing after T-cell immunotherapies, adding to the
growing combinations with selinexor that have shown benefit in
multiple myeloma and enabling further evaluation of selinexor's
role in maintaining an optimal T-cell environment.
- Selinexor has been approved in more than 40 countries and
recently achieved national reimbursement in mainland China. In 1Q 2023, the Company's license
agreement with the Menarini Group was expanded to include the
Middle East and Africa regions.
Selinexor in Endometrial Cancer (EC)
- Long-term exploratory subgroup analysis of the pre-specified
subgroup of patients with advanced or recurrent TP53
wild-type EC from the Phase 3 SIENDO study (NCT03555422) was
presented at medical conferences, with updated progression free
survival and preliminary data showing improvement in overall
survival.
- The SIENDO study manuscript was published in the Journal of
Clinical Oncology.
Selinexor in Myelofibrosis (MF)
- Presented updated results from the Phase 1 study (XPORT-MF-034)
evaluating selinexor in combination with ruxolitinib in patients
with treatment-naïve MF at several medical conferences
demonstrating encouraging spleen reduction, symptom improvement,
long-term durability and disease modification data.
- Initiated pivotal Phase 3 portion of the XPORT-MF-034 clinical
trial (NCT04562389) to assess the efficacy and safety of
once-weekly selinexor 60mg in combination with ruxolitinib in
JAKi-naïve patients with MF.
- Received Fast Track Designation from the U.S. Food and Drug
Administration (FDA) for selinexor for the treatment of patients
with MF, including primary MF, post-essential thrombocythemia MF,
and post-polycythemia vera MF.
- Planned Phase 2 XPORT-MF-044 study (NCT05980806) to evaluate
the efficacy and safety of selinexor monotherapy in subjects with
JAK inhibitor-naïve MF and moderate thrombocytopenia. Entered into
an agreement with SOBI for the supply of pacritinib as an optional
add-on in the study for eligible patients.
Eltanexor in Myelodysplastic Neoplasms (MDS)
- Reported interim data from the Phase 2 study of single-agent
eltanexor in high risk relapsed/refractory MDS (NCT02649790).
- Further development of eltanexor in MDS is on hold in line with
the Company's prioritization of its late-stage pipeline
programs.
Intellectual Property
- The United States Patent and Trademark Office issued a
certificate extending the term of the patent covering the
composition of matter of XPOVIO® (selinexor) (U.S.
patent 8,999,996) by 342 days to July 3,
2033.
- The U.S. Patent and Trademark Office has issued patents
directed toward the polymorphic form of selinexor present in
XPOVIO, pharmaceutical compositions comprising the polymorphic form
and methods of treatment using the polymorphic form and the
pharmaceutical compositions. The newly issued patents will expire
in August 2035.
Optimization of Corporate Organization
- Further positioned the Company's organization to focus on and
invest in its Phase 3 programs and drive agile execution of
business priorities, through optimization of its cost structure
with a ~ 20% reduction of the workforce, including full-time
employees and contractors.
Corporate and Financial Highlights for 2023
- Based on preliminary unaudited financial information, the
Company expects total revenue, which includes license and royalty
revenue from partners, to be approximately $33.6 million for the fourth quarter 2023 and
approximately $145.9 million for the
full year 2023, and U.S. XPOVIO net product revenue to be
approximately $25.0 million for the
fourth quarter 2023 and approximately $112.0
million for the full year 2023, meeting Company's
guidance.
- Cash, cash equivalents, restricted cash and investments as of
December 31, 2023 was approximately
$192.0 million, enabling an expected
cash runway into late 2025.
The financial information presented in this press release may be
adjusted as a result of the completion of customary annual review
and audit procedures.
Near-Term Catalysts and Operational Objectives Anticipated in
2024
- Report top-line results from pivotal Phase 3 study evaluating
an oral combination of selinexor, pomalidomide and dexamethasone in
patients with previously treated MM in 2H 2024.
- Publish and present efficacy and safety data on selinexor 40mg
in combination with pomalidomide and dexamethasone from ongoing
STOMP/028 Phase 2 studies in patients with MM.
- Report additional data on selinexor's preservation of T-cell
fitness and potential combinability with multiple agents pre or
post T-cell therapy in patients with MM.
- Complete enrollment in pivotal EC-042 Phase 3 trial in TP53
wild-type EC.
- Present updated exploratory subgroup analysis results in
patients with TP53 wild-type EC from the SIENDO study.
- Report updated results from the Phase 1 study of selinexor in
combination with ruxolitinib in patients with treatment-naïve
MF.
- Report preliminary results from Phase 2 study evaluating the
efficacy and safety of selinexor monotherapy in subjects with JAK
inhibitor-naïve MF and moderate thrombocytopenia.
- Maintain the Company's commercial foundation in the competitive
MM marketplace, driving increased XPOVIO revenues.
- Continue global launches and reimbursement approvals for
selinexor by partners in ex-U.S. territories.
Listen to the Webcast
These achievements and updates will be discussed during a
webcast presentation at the 42nd Annual J.P. Morgan Healthcare
Conference to be held on January 10,
2024, at 5:15 p.m. Eastern
Time/2:15 p.m. Pacific Time. A
live webcast of the presentation and breakout session, along with
accompanying slides, can be accessed under "Events &
Presentations" in the Investor section of the Company's website,
http://investors.karyopharm.com/events-presentations. An archived
replay will be available for 30 days following the event. The
presentation slides will also be available on the Company's website
following the event.
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 a growing number of ex-U.S.
territories and countries, including Europe, the United
Kingdom, China,
South Korea and Israel, and is marketed in those areas by
Karyopharm's global partners. 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
XPOVIO® (selinexor) is a prescription medicine
approved:
- In combination with bortezomib and dexamethasone for the
treatment of adult patients with multiple myeloma who have received
at least one prior therapy (XVd).
- In combination with dexamethasone for the treatment of adult
patients with relapsed or refractory multiple myeloma who have
received at least four prior therapies and whose disease is
refractory to at least two proteasome inhibitors, at least two
immunomodulatory agents, and an anti‐CD38 monoclonal antibody
(Xd).
- For the treatment of adult patients with relapsed or refractory
diffuse large B‐cell lymphoma (DLBCL), not otherwise specified,
including DLBCL arising from follicular lymphoma, after at least
two lines of systemic therapy. This indication is approved under
accelerated approval based on response rate. Continued approval for
this indication may be contingent upon verification and description
of clinical benefit in confirmatory trial(s).
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
https://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
Karyopharm's preliminary financial information for the fourth
quarter and full year 2023; guidance on its expected cash
runway; expectations with respect to commercialization
efforts; the ability of selinexor or eltanexor to treat patients
with multiple myeloma, endometrial cancer, myelofibrosis, diffuse
large B-cell lymphoma, myelodysplastic neoplasms and other
diseases; and expectations with respect to the clinical development
plans and potential regulatory submissions of selinexor and
eltanexor. 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 Four multiple myeloma foundations provide
financial support to Medicare patients with multiple myeloma
2 Based on Komodo claims data analysis, accessed in
October 2023
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SOURCE Karyopharm Therapeutics Inc.