On December 12, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported updated results from the Phase 1 portion of its study evaluating the safety and efficacy of once-weekly selinexor in combination with standard dose ruxolitinib in patients with treatment-naïve myelofibrosis (NCT04562389) (Press release, Karyopharm, DEC 12, 2022, View Source [SID1234625073]). The data, featured in a poster presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) 2022 Annual Meeting and Exposition, show that the combination of selinexor with ruxolitinib achieved rapid and sustained spleen responses, encouraging improvements in symptoms and stabilization of hemoglobin levels in patients with treatment-naïve myelofibrosis.

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As of October 21, 2022, 24 patients had been assigned to either a 40 mg or 60 mg once weekly dose of selinexor, in combination with ruxolitinib 15/20 mg BID (twice daily). At week 24, 92% of efficacy evaluable patients (11 out of 12) demonstrated ≥35% reduction in spleen volume (SVR35). Ongoing reductions in SVR were seen from baseline to week 12 and week 24, with a 45% median reduction at week 12 and a 49% median reduction at week 24. 67% of the evaluable patients for symptom response (4 out of 6) at week 24 achieved ≥50% reduction (TSS50). 57% of transfusion-independent patients (13 out of 23) maintained or improved their hemoglobin levels.

"As an oral agent with a unique mechanism of action, selinexor has previously shown single-agent activity in myelofibrosis patients," said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. "As a result, we believe that the combination of selinexor and ruxolitinib has the potential to meaningfully build upon the current standard of care, which is ruxolitinib alone, for patients with treatment-naïve myelofibrosis. We look forward to further developing this combination in the randomized phase of the study."

The safety population was comprised of 24 patients, all of whom received at least one dose of selinexor. The most common adverse events (AEs) were nausea (75%), anemia (62%) and fatigue (58%), the majority of which were grades 1-2. The most common reported grade 3-4 treatment-emergent AEs were anemia (37%) and thrombocytopenia (21%), both of which were reversible.

"In the Phase 1 portion of the study, encouraging efficacy was observed across the relevant efficacy endpoints of SVR35, TSS50, and hemoglobin stabilization and a generally manageable safety profile was observed regardless of dose. Furthermore, I find the rapid spleen reduction as early as week 12 especially notable, along with early signs of durability," said Dr. Haris Ali, City of Hope Comprehensive Cancer Center. "These data support the potential of an oral XPO1 inhibitor, in combination with a JAK inhibitor, to deliver significant benefits for patients with myelofibrosis."

Investor and Analyst Event on Selinexor Data in Patients with Treatment-Naïve Myelofibrosis at ASH (Free ASH Whitepaper) 2022

Karyopharm will host a webcast today, December 12, 2022, at 8:30 a.m. Eastern Time (7:30 a.m. CT local time), featuring key opinion leaders Dr. Haris Ali, City of Hope Comprehensive Cancer Center and Dr. Srdan Verstovsek, MD Anderson Cancer Center. Drs. Ali and Verstovsek will discuss the updated data on selinexor in combination with ruxolitinib as well as the current treatment landscape and unmet medical need in treating patients with myelofibrosis, respectively.

To access the event, the live audio webcast and slides will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will 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 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: [email protected]

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.