NEWTON, Mass., Nov. 4, 2021 /PRNewswire/ -- Karyopharm
Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical
company pioneering novel cancer therapies, today announced that an
abstract detailing new data from a Phase 2 study evaluating
selinexor, a first-in-class, oral Selective Inhibitor of Nuclear
Export (SINE) compound, in patients with myelofibrosis (MF)
previously treated with JAK inhibition has been selected for an
oral presentation at the upcoming American Society of Hematology
(ASH) 2021 Annual Meeting and Exposition in Atlanta, GA on December
11-14, 2021.
"JAK inhibition is the current standard of care for patients
with myelofibrosis; however, patients whose disease fails treatment
with ruxolitinib have a poor prognosis, with an expected survival
of approximately 14 months, and there are no approved treatment
options other than JAK inhibitors," said Srinivas Tantravahi, MBBS, MRCP, University of Utah Hospital and principal
investigator of the Phase 2 study. "Interim results from this Phase
2 study demonstrated that once weekly single agent oral selinexor
resulted in compelling spleen volume reduction rates in
myelofibrosis patients who received at least 24 weeks of treatment,
with 33% of those patients achieving a response, defined as
≥35% SVR. In addition to spleen responses, there was
improvement in anemia status and symptom scores in these patients.
The responses were durable with the first patient on treatment for
more than two years. The sustained responses and well-tolerated
safety profile highlight selinexor's potential in patients with
myelofibrosis who have either progressed following ruxolitinib or
cannot tolerate JAK inhibition. We look forward to sharing these
exciting results with the broader medical and scientific community
at ASH this year."
"Once weekly, low-dose selinexor is an oral agent with a unique
mechanism of action that has demonstrated strong single-agent
activity in myelofibrosis patients with disease refractory to
ruxolitinib," said Jatin Shah, MD,
Chief Medical Officer of Karyopharm. "Importantly, there are no
other classes of drug approved other than JAK inhibitors and a new
class of effective drugs is a critical need for patients. Based on
these encouraging data, we look forward to dosing the first patient
in a new, company-sponsored Phase 2 study evaluating single-agent
selinexor versus physician's choice in patients with previously
treated myelofibrosis during the fourth quarter of 2021."
Results from the Phase 2 Study Evaluating Selinexor in
Patients with MF Refractory or Intolerant to JAK Inhibitors
The results were based on the open label, prospective,
investigator-initiated single center study in adult patients with
primary or secondary MF with resistance or intolerance to JAK
inhibitor therapy (NCT03627403). Selinexor was administered orally
at a dose of 80mg or 60mg once weekly to 12 patients. The primary
endpoint of the study is to assess the efficacy of selinexor on
SVR. Median duration of prior JAK inhibitor therapy was 22 months
and 11 out of 12 patients had MF refractory to ruxolitinib.
As of the data cutoff, the median duration of treatment was 36
weeks. In the nine patients who were on treatment for over 24
weeks, SVR of ≥25% and 35% occurred in four (44%) and three (33%)
patients, respectively. The most common treatment related adverse
event was weight loss (grade 2 in four patients and grade 3 in one
patient). This was manageable with treatment interruption and dose
reduction, except in one patient who discontinued treatment.
Overall, selinexor demonstrated single-agent activity with
sustained spleen responses in patients with JAK inhibitor
refractory MF and long-term administration of selinexor was well
tolerated. Updated data will be presented at the meeting.
Company to Host Investor Day Event
Karyopharm will host an Investor Day event on Wednesday, December 8, 2021 from 10:00 a.m. to 12:30 p.m. ET to outline its
commercial and pipeline priorities and objectives. The event will
feature presentations from Karyopharm management and recognized
thought leaders in multiple myeloma, gynecological malignancies,
and other core focus indications. The event will take place
virtually and will be accessible via conference call and webcast.
Full details will be made available closer to the Investor Day.
Details for the ASH 2021 abstracts are as follows:
In total, 17 abstracts were selected for presentation at the
meeting, including five oral presentations and 12 posters.
Oral Presentations
Title: A Phase 2 Study to Evaluate the Efficacy and
Safety of Selinexor in Patients with Myelofibrosis Refractory or
Intolerant to JAK Inhibitors
Presenter: Srinivas
Tantravahi, University of
Utah
Abstract #: 143
Session Type: Oral
Presentation
Session: Myeloproliferative Syndromes: Clinical and
Epidemiological: Non-JAK Inhibitor Therapies for Myelofibrosis
Date and Time: Saturday, December 11,
2021 at 1:00 p.m. ET
Title: Transcriptomic Correlates of Response to Selinexor
in Multiple Myeloma Reveal a Predictive Signature
Presenter: Paula Restrepo,
Icahn School of Medicine at Mount Sinai
Abstract #: 457
Session Type: Oral Presentation
Session: Multiple Myeloma and Plasma Cell Dyscrasias:
Clinical and Epidemiological: Multiple Myeloma and Waldenstrom
Macroglobulinemia: Exploring Biomarkers in the Era of Personalized
Medicine
Date and Time: Sunday, December 12,
2021 at 12:00 p.m. ET
Title: Enhanced p53 Activation by Dual Inhibition of MDM2
and XPO1 Disrupts MYC Transcriptional Program and Restores
Sensitivity to BCL-2 Inhibition in Ven/HMA Resistant AML
Presenter: Yuki Nishida, Saga
University
Abstract #: 505
Session Type: Oral Presentation
Session: Molecular Pharmacology and Drug Resistance: Myeloid
Neoplasms: Novel Strategies to Overcome Resistance to BCL-2
Inhibition
Date and Time: Sunday, December 12,
2021 at 4:30 p.m. ET
Title: Rationale for Selinexor Treatment in
Daratumumab-Refractory MM Patients Identified by Paired Ex
Vivo Drug Sensitivity and RNA-Seq
Presenter: Suresh Kumar
Balasubramanian, Wayne State
University
Abstract #: 683
Session Type: Oral Presentation
Session: Molecular Pharmacology and Drug Resistance:
Lymphoid Neoplasms: Targeting
Mitochondrial Survival Pathways
Date and Time: Monday, December 13,
2021 at 3:45 p.m. ET
Title: Comparison of Salvage Autologous Hematopoietic
Cell Transplantation with Outcomes Following Selinexor Combinations
Among Double/Triple Refractory Myeloma Patients
Presenter: Praneeth Sudalagunta, H Lee Moffitt Cancer
Ctr
Abstract #: 893
Session Type: Oral Presentation
Session: Multiple Myeloma and Plasma Cell Dyscrasias: Basic
and Translational: Myeloma Pathogenesis and Novel Targets
Date and Time: Monday, December 13,
2021 at 7:15 p.m. ET
Poster Presentations
Title: Efficacy and Safety of Selinexor-Containing
Regimens in Patients with Multiple Myeloma Previously Treated with
Anti-CD38 Monoclonal Antibodies (αCD38 mAb)
Presenter: Suzanne Lentzsch, Columbia University Irving Medical Center
Abstract #: 1651
Session Type: Poster Presentation
Session: Myeloma and Plasma Cell Dyscrasias:
Clinical-Prospective Therapeutic Trials: Poster I
Date and Time: Saturday, December 11,
2021 at 5:30 – 7:30 p.m.
ET
Title: Effects of Cytogenetic Risk on Outcomes in
Multiple Myeloma Treated with Selinexor, Bortezomib, and
Dexamethasone (XVd)
Presenter: Nizar Bahlis, University of Calgary
Abstract #: 1634
Session Type: Poster Presentation
Session: Multiple Myeloma and Plasma Cell Dyscrasias:
Clinical and Epidemiological: Poster I
Date and Time: Saturday, December 11,
2021 at 5:30 – 7:30 p.m.
ET
Title: Selinexor in Combination with
Daratumumab-Bortezomib and Dexamethasone for the Treatment of
Relapse or Refractory Multiple Myeloma: Initial Results of the
Phase 2, Open-label, Multicenter GEM-SELIBORDARA Study
Presenter: Paula Rodríguez- Otero, Clínica Universidad de Navarra
Abstract #: 1677
Session Type: Poster Presentation
Session: Myeloma and Plasma Cell Dyscrasias:
Clinical-Prospective Therapeutic Trials: Poster I
Date and Time: Saturday, December 11,
2021 at 5:30 – 7:30 p.m.
ET
Title: Once Weekly Oral Selinexor, Pomalidomide, and
Dexamethasone in Relapsed Refractory Multiple Myeloma
Presenter: Darrell White,
QEII Health Sciences Center, Dalhousie
University
Abstract #: 2748
Session Type: Poster Presentation
Session: Myeloma and Plasma Cell Dyscrasias:
Clinical-Prospective Therapeutic Trials: Poster II
Date and Time: Sunday, December 12,
2021 at 6:00 – 8:00 p.m.
ET
Title: Selinexor-Based Regimens in Patients with Multiple
Myeloma after Prior Anti-B-Cell Maturation Antigen Treatment
Presenter: Muhamed Baljevic,
University of Nebraska Medical
Center
Abstract #: 2751
Session Type: Poster Presentation
Session: Myeloma and Plasma Cell Dyscrasias:
Clinical-Prospective Therapeutic Trials: Poster II
Date and Time: Sunday, December 12,
2021 at 6:00 – 8:00 p.m.
ET
Title: Single Cell RNA Sequencing of a Selinexor Clinical
Trial Reveals Overexpression of Alternative Nuclear Export Pathways
Associated with Resistance to Selinexor in RRMM Patients
Presenter: Yael Cohen, Tel Aviv Sourasky Medical
Center
Abstract #: 2725
Session Type: Poster Presentation
Session: Multiple Myeloma and Plasma Cell Dyscrasias:
Clinical and Epidemiological: Poster I
Date and Time: Sunday, December 12,
2021 at 6:00 – 8:00 p.m.
ET
Title: Selinexor Enhances NK Cell Activation Against
Lymphoma Cells Via Downregulation of HLA
Presenter: Matthew Blunt,
University of Southampton
Abstract #: 2411
Session Type: Poster Presentation
Session: Lymphomas: Translational—Non-Genetic: Poster
II
Date and Time: Sunday, December 12,
2021 at 6:00 – 8:00 p.m.
ET
Title: Molecular Response Patterns in Relapsed/Refractory
AML Patients Treated with Selinexor and Chemotherapy
Presenter: Piroska Klement,
Hannover Medical School
Abstract #: 2369
Session Type: Poster Presentation
Session: Acute Myeloid Leukemias: Biomarkers, Molecular
Markers and Minimal Residual Disease in Diagnosis and Prognosis:
Poster II
Date and Time: Sunday, December 12,
2021 at 6:00 – 8:00 p.m.
ET
Title: Updated Efficacy of Eltanexor Monotherapy in
Patients with Higher Risk Hypomethylating Myelodysplastic Syndrome
Primary Refractory to Hypomethylating Agents
Presenter: Sangmin Lee, Weill
Cornell Medical College
Abstract #: 3676
Session Type: Poster Presentation
Session: Myelodysplastic Syndromes — Clinical and
Epidemiological: Poster III
Date and Time: Monday, December 13,
2021 at 6:00 – 8:00 p.m.
ET
Title: Clinical Outcomes in Patients with Dose Reduction
of Selinexor in Combination with Bortezomib, and Dexamethasone
(XVd) in Previously Treated Multiple Myeloma from the BOSTON Study
Presenter: Sundar Jagannath, Mount Sinai School of
Medicine
Abstract #: 3793
Session Type: Poster Presentation
Session: Multiple Myeloma and Plasma Cell Dyscrasias:
Clinical and Epidemiological: Poster III
Date and Time: Monday, December 13,
2021 at 6:00 – 8:00 p.m.
ET
Title: Selinexor in Combination with R-GDP for Patients
with Relapsed/Refractory B-Cell Lymphoma: SELINDA Phase Ib LYSA
Study
Presenter: Marie Maerevoet, Jules Bordet Institute
Abstract #: 1411
Session Type: Poster Presentation
Session: Aggressive Lymphomas: Prospective Therapeutic
Trials: Poster I
Date and Time: Saturday, December 11,
2021 at 5:30 – 7:30 p.m.
ET
Title: A Phase 2/3, Multicenter Randomized Study of
Rituximab-Gemcitabine-Dexamethasone-Platinum (R-GDP) with or
without Selinexor in Patients with Relapsed/Refractory Diffuse
Large B-Cell Lymphoma (RR DLBCL)
Presenter: Seung Tae Lee, University of Maryland School of Medicine
Abstract #: 1420
Session Type: Poster Presentation
Session: 626. Aggressive Lymphomas: Prospective Therapeutic
Trials: Poster I
Date and Time: Saturday, December 11,
2021, 5:30-7:30PM ET
About XPOVIO® (selinexor)
XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear
Export (SINE) compound. XPOVIO functions by selectively binding to
and inhibiting the nuclear export protein exportin 1 (XPO1, also
called CRM1). XPOVIO blocks the nuclear export of tumor suppressor,
growth regulatory and anti-inflammatory proteins, leading to
accumulation of these proteins in the nucleus and enhancing their
anti-cancer activity in the cell. The forced nuclear retention of
these proteins can counteract a multitude of the oncogenic pathways
that, unchecked, allow cancer cells with severe DNA damage to
continue to grow and divide in an unrestrained fashion. Karyopharm
received accelerated U.S. Food and Drug Administration (FDA)
approval of XPOVIO in July 2019 in
combination with dexamethasone for the treatment of adult patients
with relapsed refractory multiple myeloma (RRMM) 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. NEXPOVIO® (selinexor)
has also been granted conditional marketing authorization for adult
patients with heavily pretreated multiple myeloma by the European
Commission. Karyopharm's supplemental New Drug Application (sNDA)
requesting an expansion of its indication to include the treatment
for patients with multiple myeloma after at least one prior therapy
was approved by the FDA on December 18,
2020. In June 2020, Karyopharm
received accelerated FDA approval of XPOVIO for its second
indication in adult patients with relapsed or refractory diffuse
large B-cell lymphoma (DLBCL), not otherwise specified, including
DLBCL arising from follicular lymphoma, after at least 2 lines of
systemic therapy. Selinexor is also being evaluated in several
other mid-and later-phase clinical trials across multiple cancer
indications, including as a potential backbone therapy in
combination with approved myeloma therapies (STOMP) and in
endometrial cancer (SIENDO), among others. Additional Phase 1,
Phase 2 and Phase 3 studies are ongoing or currently planned,
including multiple studies in combination with approved therapies
in a variety of tumor types to further inform Karyopharm's clinical
development priorities for selinexor. Additional clinical trial
information for selinexor is available at
www.clinicaltrials.gov.
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 2
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 and dedicated to the discovery, development, and
commercialization of first-in-class drugs directed against nuclear
export for the treatment of cancer and other diseases. Karyopharm's
Selective Inhibitor of Nuclear Export (SINE) compounds function by
binding with and inhibiting the nuclear export protein XPO1 (or
CRM1). Karyopharm's lead compound, XPOVIO® (selinexor), is approved
in the U.S. in multiple hematologic malignancy indications,
including in combination with Velcade® (bortezomib) and
dexamethasone for the treatment of adult patients with multiple
myeloma after at least one prior therapy, in combination with
dexamethasone for the treatment of adult patients with heavily
pretreated multiple myeloma and as a monotherapy for the treatment
of adult patients with relapsed or refractory diffuse large B-cell
lymphoma. NEXPOVIO® (selinexor) has also been granted conditional
marketing authorization in combination with dexamethasone for adult
patients with heavily pretreated multiple myeloma by the European
Commission. 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
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
ability of selinexor or eltanexor to treat patients with multiple
myeloma, diffuse large B-cell lymphoma, solid tumors and other
diseases and expectations related to future clinical development
and potential regulatory submissions of selinexor or 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;
that regulators will grant confirmatory approval in the European
Union based on the BOSTON study in
adult patients with multiple myeloma; 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 September 30,
2021, which was filed with the Securities and Exchange
Commission (SEC) on November 3, 2021,
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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