Karyopharm Announces Dosing of First Patient in a New Phase 2 Study Evaluating Single-Agent Selinexor Versus Physician's Choice in Previously Treated Myelofibrosis

Rhea-AI Summary

Karyopharm Therapeutics (KPTI) has commenced a Phase 2 study (XPORT-MF-035) to assess the efficacy of oral selinexor in myelofibrosis patients previously treated with JAK inhibitors. The trial aims to enroll up to 112 patients, evaluating the primary endpoint of spleen volume reduction. This study follows promising results from the ESSENTIAL trial, where 33% of patients experienced significant SVR after 24 weeks of treatment. The company emphasizes its commitment to addressing unmet medical needs in serious conditions like myelofibrosis.

Positive

• Initiation of Phase 2 study for selinexor in myelofibrosis could provide crucial data on its efficacy.
• Previous ESSENTIAL trial results showed 33% of patients achieved ≥35% spleen volume reduction.
• Selinexor's potential to address unmet needs in patients intolerant to or progressing after JAK inhibitors.

Negative

• None.

NEWTON, Mass., Dec. 6, 2021 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced dosing of the first patient in a new Phase 2 study evaluating oral selinexor, the Company's first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound, as a monotherapy versus physician's choice in patients with myelofibrosis (MF) previously treated with a JAK 1/2 inhibitor (XPORT-MF-035; NCT04562870).

This randomized, multi-center, open-label Phase 2 study is designed to evaluate the safety and efficacy of selinexor monotherapy and is expected to enroll up to 112 patients, who will be randomized 1:1 to receive either low dose, once-weekly oral selinexor or physician's standard treatment choice (per clinical practice). The primary endpoint of the study is the percentage of patients with spleen volume reduction (SVR) of ≥35% from baseline as assessed by an Independent Review Committee. The first patient has been dosed at the Instituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) Meldola, Italy, by the Lead Principal Investigator, Dr. Alessandro Lucchesi, Sr. Consultant and Research Hematologist under the guide of Professor Giovanni Martinelli, the Chief Scientific Director.

Initiation of this Phase 2 study follows encouraging preliminary data from the Phase 2 ESSENTIAL trial, which will be highlighted in an oral presentation given by Srinivas Tantravahi, MBBS, MRCP, University of Utah Hospital, at the upcoming American Society of Hematology (ASH) 2021 Annual and Exposition on Saturday, December 11, 2021 at 1:00 p.m. ET. In the investigator-sponsored ESSENTIAL study (NCT03627403), which is evaluating selinexor in patients with MF previously treated with a JAK inhibitor, preliminary data showed that 33% of patients that received at least 24 weeks of selinexor treatment achieved ≥35% SVR. The responses were durable, and the first patient remained on study for more than two years. Patients had a median duration of 22 months of prior JAK inhibitor therapy with 11 out of 12 patients having disease refractory to ruxolitinib.

"As part of our strategic imperatives and pipeline priorities, we remain focused on diseases with the highest unmet needs and greatest potential to make an impact in patient outcomes," said Sharon Shacham, PhD, MBA, Co-Founder and Chief Scientific Officer of Karyopharm. "Myelofibrosis is a serious and life–threatening blood cancer defined by stem cell–derived clonal myeloproliferation, bone marrow fibrosis, anemia, enlarged spleen, low blood counts and short survival. With JAK inhibitors being the only class of drugs approved for this disease, there remains limited therapeutic options for patients who either progress following treatment with a JAK inhibitor or are intolerant. We believe selinexor has the potential to hold an important place in the myelofibrosis treatment paradigm and with dosing of the first patient underway, we plan to provide updates as the study progresses."

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 two 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 Karyopharm's expectations and plans relating to selinexor and eltanexor for the treatment of hematologic malignancies or certain solid tumors; the expected design of the Company's clinical trials; and the therapeutic potential of and potential clinical development plans for Karyopharm's drug candidates, especially 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 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 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 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 press release are the property of their respective owners.

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SOURCE Karyopharm Therapeutics Inc.

FAQ

What is the purpose of the KPTI Phase 2 study involving selinexor?

The Phase 2 study aims to evaluate the safety and efficacy of oral selinexor as a monotherapy in patients with myelofibrosis who have previously been treated with JAK inhibitors.

What are the primary endpoints of the KPTI selinexor study?

The primary endpoint is the percentage of patients achieving a spleen volume reduction of ≥35% from baseline, assessed by an Independent Review Committee.

What were the results of the previous ESSENTIAL trial for selinexor?

In the ESSENTIAL trial, 33% of patients receiving selinexor treatment achieved a ≥35% spleen volume reduction after at least 24 weeks.

How many patients are expected to enroll in the KPTI Phase 2 study?

The study is expected to enroll up to 112 patients.

What is Karyopharm Therapeutics' approach to myelofibrosis treatment?

Karyopharm focuses on developing therapies like selinexor to address the unmet medical needs of patients with myelofibrosis, particularly those who have limited options after JAK inhibitor therapy.