Karyopharm Announces XPOVIO® (Selinexor) Clinical Data to be Presented at the American Society of Hematology 2020 Annual Meeting
NEWTON, Mass., Nov. 4, 2020 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that twenty-one abstracts have been selected for virtual presentation, including two oral presentations, at the upcoming American Society of Hematology (ASH) 2020 Annual Meeting taking place December 5-8, 2020. Key abstracts to be presented at the meeting will feature clinical data for XPOVIO® (selinexor), the Company's first in class, oral SINE compound, including: (i) updated data from the Pomalyst® (pomalidomide), Kyprolis® (carfilzomib) and Revlimid® (lenalidomide) arms of the Phase 1b/2 STOMP study evaluating XPOVIO in combination with backbone therapies in patients with relapsed or refractory multiple myeloma; (ii) several new subgroup analyses from the pivotal Phase 3 BOSTON study evaluating once weekly XPOVIO in combination with once weekly Velcade® (bortezomib) and low-dose dexamethasone against standard twice weekly Velcade in adult patients with multiple myeloma who had received one to three prior lines of therapy; and (iii) new subgroup analyses from the Phase 2b SADAL study evaluating XPOVIO in relapsed or refractory diffuse large B-cell lymphoma (DLBCL).
"Our tradition of having a strong presence at the ASH annual meeting continues this year and we are excited to share important clinical data from a variety of our XPOVIO clinical studies," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. "In total, twenty-one abstracts have been selected, including an oral presentation highlighting the all-oral regimen of XPOVIO and Pomalyst® from the ongoing STOMP study. Additionally, updated data from two other arms of the STOMP study will also be presented, including the arm investigating XPOVIO and Kyprolis® as well as the arm investigating XPOVIO and Revlimid®. In all three arms, the response rates and safety profile continue to be encouraging. In addition, we look forward to several poster presentations describing a variety of subanalyses from the Phase 3 BOSTON study in important subgroups such as older, frail patients, patients previously treated with proteasome inhibitors, and patients with high risk cytogenetics, among others."
Karyopharm plans to host a virtual investor and analyst event to discuss the Company's pipeline of clinical programs and highlights from the ASH 2020 data presentations. Details for this event, including date, time, and log-in information will be announced in the coming weeks. A live webcast of the presentation will be accessed under "Events & Presentations" in the Investors section of the Company's website at http://investors.karyopharm.com/events-presentations. A replay of the webcast will be archived on the Company's website for 90 days following the event.
Details for the ASH 2020 presentations are as follows:
XPOVIO (selinexor) – Company-Sponsored Studies – Oral Presentation – Multiple Myeloma
Title: Selinexor in combination with pomalidomide and dexamethasone (SPd) for treatment of patients with relapsed refractory multiple myeloma (RRMM).
XPOVIO (selinexor) – Company-Sponsored Studies – Poster Presentations – Multiple Myeloma
Title: Selinexor in combination with carfilzomib and dexamethasone, all once weekly (SKd), for patients with relapsed/refractory multiple myeloma
Title: Selinexor, lenalidomide and dexamethasone (SRd) for patients with relapsed/refractory and newly diagnosed multiple myeloma
Title: Effect of prior treatment with proteasome inhibitors on the efficacy and safety of once-weekly selinexor, bortezomib, and dexamethasone in comparison with twice weekly bortezomib and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis from the BOSTON study
Title: Impact of prior therapies on the safety and efficacy of once-weekly selinexor, bortezomib, and dexamethasone compared with twice-weekly bortezomib and dexamethasone in relapsed ore refractory multiple myeloma: results from the BOSTON study
Title: Once weekly selinexor, bortezomib, and dexamethasone versus twice weekly bortezomib and dexamethasone in relapsed ore refractory multiple myeloma: age and frailty subgroup analyses from the phase 3 BOSTON study
Title: Once weekly selinexor, bortezomib, and dexamethasone (SVd) versus twice weekly bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma: high-risk cytogenetic risk planned subgroup analyses from the phase 3 BOSTON study
Title: Peripheral neuropathy symptoms, pain and functioning in relapsed or refractory MM patients treated with selinexor, bortezomib, and dexamethasone
XPOVIO (selinexor) – Company-Sponsored – Poster Presentations – Lymphoma
Title: Effect of age on the efficacy and safety of single agent oral selinexor in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL): a post-hoc analysis from the SADAL pivotal study
Title: Selinexor efficacy and safety are independent of renal function in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL): a post-hoc analysis from the pivotal phase 2b SADAL study
Title: A six-protein activity signature defines favorable response to selinexor treatment for patients with diffuse large B-cell lymphoma (DLBCL)
XPOVIO (selinexor) – Investigator-Sponsored – Oral Presentations – Lymphoma
Title: Inhibiting the Nuclear Exporter XPO1 and the Antiapoptotic Factor BCL2 Is Synergistic in XPO1 Mutant and Wildtype Lymphoma
XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Lymphoma
Title: Selinexor in combination with R-CHOP for frontline treatment of non-Hodgkin lymphoma: results of a phase 1b study
Title: A Phase I Investigator Sponsored Trial of Selinexor (KPT-330) and Rituximab, Ifosfamide, Carboplatin and Etoposide in Patients with Relapsed or Refractory Aggressive B-Cell Lymphomas
Title: XPO1 Relieves MYC-Induced Replication Stress Limiting the Immunogenicity of DLBCL Cells
Title: The Expression of Chromosome Region Maintenance Protein 1 (CRM1) in Large Cell Lymphoma
XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Leukemia
Title: Frontline selinexor and chemotherapy is highly active in older adults with AML
Title: Exportin-1 (XPO1) Inhibition Sequesters p53 from MDM2 and MDM4 and Is Highly Synergistic with MDM2 Inhibition in Inducing Apoptosis in Wild-Type p53 Acute Myeloid Leukemias
XPOVIO (selinexor) – Investigator-Sponsored – Poster Presentations – Other
Title: CRISPR/Cas9 Chemogenetic Profiling Identifies Candidate Biomarker Genes That Modulate Sensitivity to Selinexor
Title: Salicylates Potentiate and Broaden CRM1 Inhibitor Anti-Tumor Activity Via S-Phase Arrest and Impaired DNA-Damage Repair
KPT-9274 – Investigator-Sponsored – Poster Presentations – Other
Title: Nicotinamide Phosphoribosyltransferase Inhibitors Induce Apoptosis of AML Stem Cells through Dysregulation of Lipid Metabolism
About XPOVIO® (selinexor)
For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at:
Tel: +1 (888) 209-9326
IMPORTANT SAFETY INFORMATION
Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.
Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Institute platelet transfusion and/or other treatments as clinically indicated. Monitor patients for signs and symptoms of bleeding and evaluate promptly. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.
Neutropenia: XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. Neutropenia and febrile neutropenia occurred in patients with MM and in patients with DLBCL.
Obtain white blood cell counts with differential at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of concomitant infection and evaluate promptly. Consider supportive measures, including antimicrobials and growth factors (e.g., G-CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction (AR).
Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.
Nausea/Vomiting: Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents prior to and during treatment with XPOVIO. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Administer intravenous fluids to prevent dehydration and replace electrolytes as clinically indicated.
Diarrhea: Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide standard anti-diarrheal agents, administer intravenous fluids to prevent dehydration, and replace electrolytes as clinically indicated.
Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Interrupt, reduce dose, or permanently discontinue based on severity of ARs. Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.
Hyponatremia: XPOVIO can cause severe or life-threatening hyponatremia. Hyponatremia developed in patients with MM and in patients with DLBCL.
Monitor sodium level at baseline and throughout treatment. Monitor more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Assess hydration status and manage hyponatremia per clinical guidelines, including intravenous saline and/or salt tablets as appropriate and dietary review. Interrupt, reduce dose, or permanently discontinue based on severity of the AR.
Serious Infection: XPOVIO can cause serious and fatal infections. Most infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.
Monitor for signs and symptoms of infection, and evaluate and treat promptly.
Neurological Toxicity: XPOVIO can cause life-threatening neurological toxicities.
Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.
Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, until the neurological toxicity fully resolves. Optimize hydration status, hemoglobin level, and concomitant medications to avoid exacerbating dizziness or mental status changes. Institute fall precautions as appropriate.
Embryo-Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.
Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.
The most common adverse reactions (ARs) in ≥20% of patients with MM are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.
The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.
In patients with MM, fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia.
In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients.
USE IN SPECIFIC POPULATIONS
In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.
Clinical studies in patients with relapsed or refractory DLBCL did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.
The effect of end-stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.
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.
Please see XPOVIO Full Prescribing Information available at www.XPOVIO.com.
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 novel first-in-class drugs directed against nuclear export and related targets for the treatment of cancer and other major 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), received accelerated approval from the U.S. Food and Drug Administration (FDA) in July 2019 in combination with dexamethasone as a treatment for patients with heavily pretreated multiple myeloma. In June 2020, XPOVIO was approved by the FDA as a treatment for patients with relapsed or refractory diffuse large B-cell lymphoma. A Marketing Authorization Application for selinexor for patients with heavily pretreated multiple myeloma is also currently under review by the European Medicines Agency. 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.
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 beliefs regarding the ability of selinexor 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 XPOVIO. 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 agree that selinexor qualifies for conditional approval in the E.U. as a result of data from the STORM study or confirmatory approval in the U.S. or EU based on the BOSTON study in patients with relapsed or refractory multiple myeloma; 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 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 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 obtain and maintain requisite regulatory approvals and to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development of drug candidates by Karyopharm's competitors for diseases in which Karyopharm is currently developing its drug candidates; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any drug candidates it is developing. 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, 2020, which was filed with the Securities and Exchange Commission (SEC) on November 2, 2020, 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.
Velcade® is a registered trademark of Takeda Pharmaceutical Company Limited
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Company Codes: NASDAQ-NMS:KPTI