Karyopharm Submits Supplemental New Drug Application to the FDA for XPOVIO® (selinexor) Plus Ruxolitinib for Patients with Myelofibrosis

Rhea-AI Summary

Karyopharm Therapeutics (Nasdaq: KPTI) has submitted a supplemental New Drug Application (sNDA) to the U.S. FDA seeking Accelerated Approval for XPOVIO (selinexor) in combination with ruxolitinib to treat patients with myelofibrosis. The company has also requested Priority Review, which, if granted, could shorten FDA review to six months.

According to Karyopharm, the sNDA is supported in part by Phase 3 SENTRY trial data in JAK inhibitor–naïve myelofibrosis patients (N=353), using spleen volume reduction ≥35% at week 24 and symptom score change as co‑primary endpoints. The company expects to receive FDA filing acceptance and timeline information in Q4 2026 and plans to use long‑term overall survival data from SENTRY as confirmatory evidence for potential conversion from accelerated to traditional approval. Selinexor already holds U.S. and EU orphan designations for myelofibrosis and a U.S. Fast Track designation.

Positive

• sNDA filed for XPOVIO plus ruxolitinib in myelofibrosis, seeking Accelerated Approval
• Priority Review requested, which if granted could allow a six‑month FDA review
• Regulatory package supported by Phase 3 SENTRY trial in 353 JAKi‑naïve patients
• Selinexor holds Orphan Drug and Fast Track designations for myelofibrosis in the U.S.
• European Commission granted Orphan Medicinal Product designation for selinexor in myelofibrosis

Negative

• Regulatory outcome remains uncertain; FDA filing acceptance and review timelines only expected in Q4 2026
• Accelerated approval would depend on FDA agreeing that SVR35 is a reasonably likely surrogate for overall survival

Market Reaction – KPTI

+4.28% $1.95 2.4x vol

15m delay

+4.28% Vs previous close

$1.95 Last Price

$1.87 $1.97 Day Range

$44.23M Market Cap

2.4x Rel. Volume

Following this news, KPTI has gained 4.28%, reflecting a moderate positive market reaction. Our momentum scanner has triggered 2 alerts so far, indicating moderate trading interest and price volatility. The stock is currently trading at $1.95. Trading volume is elevated at 2.4x the average, suggesting notable buying interest.

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Market Context

Clinical-tag history showed an average move of -20.08%, adding a cautionary platform benchmark to th...

Analysis

Clinical-tag history showed an average move of -20.08%, adding a cautionary platform benchmark to this submission. The FDA's SVR35 surrogate assessment and confirmatory overall-survival plan remained key watchpoints, alongside high short positioning.

Key Figures

Priority review timeline: six months FDA filing review period: 60 days Trial enrollment: 353 patients +4 more

7 metrics

Priority review timeline six months if Priority Review is granted

FDA filing review period 60 days sNDA filing acceptance review

Trial enrollment 353 patients Phase 3 SENTRY trial

Selinexor dose 60 mg once-weekly SENTRY regimen

Randomization 2-to-1 patients randomized to the selinexor arm

SVR35 threshold ≥ 35% spleen volume reduction surrogate endpoint

SVR35 assessment week 24 SENTRY co-primary endpoint

Previous Clinical trial Reports

5 past events · Latest: Jul 30 (Negative)

Same Type Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
Jul 30	Phase 3 trial result	Negative	-72.6%	Endometrial cancer trial missed its primary progression-free survival endpoint.
Jun 02	Phase 3 data presentation	Positive	-6.0%	SENTRY data received selection for a top late-breaking EHA presentation.
Jun 02	Phase 3 data presentation	Positive	-6.0%	SENTRY data showed significant SVR35 improvement and a favorable survival signal.
Apr 21	Phase 3 data presentation	Positive	+2.6%	SENTRY data was accepted for a late-breaking ASCO oral presentation.
Mar 24	Phase 3 trial result	Negative	-18.3%	SENTRY met the spleen endpoint but missed the symptom improvement endpoint.

24h Move is the share-price change in the day after each event; other market factors may also have contributed.

Pattern Detected

KPTI's clinical-news history showed divergence when favorable SENTRY-related updates were followed by declines, while negative trial news aligned with selloffs.

Key Terms

snda, accelerated approval, priority review, xpo1 inhibitor

4 terms

snda regulatory

"submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration"

A SNDA (Subordination, Non‑Disturbance and Attornment Agreement) is a legal pact among a property owner’s lender, the owner’s tenants, and sometimes the landlord that sets who keeps lease rights if the property is sold or a mortgage is enforced. Think of it as a rulebook that decides whether a tenant can stay and keep paying rent or must answer to a new owner after a foreclosure. For investors, an SNDA matters because it protects predictable rental income, clarifies who has priority on claims against a property, and therefore affects a property’s value and the security of related loans.

accelerated approval regulatory

"seeking Accelerated Approval for XPOVIO® (selinexor) in combination with ruxolitinib"

Accelerated approval is a process that allows new medical treatments to be approved more quickly than usual if they address serious or life-threatening conditions and show promising early results. For investors, it signals that a treatment may reach the market sooner, potentially boosting a company's prospects, but it also involves some uncertainty since full evidence of effectiveness is still being gathered.

priority review regulatory

"Karyopharm requested Priority Review of the application"

Priority review is a regulatory fast-track that shortens the time an agency spends evaluating a drug, vaccine or medical device application so a decision comes sooner than normal. For investors, it matters because a faster review is like an express lane to market: it can speed revenue potential and reduce regulatory uncertainty, but it does not guarantee approval and still requires the product to meet safety and effectiveness standards.

xpo1 inhibitor technical

"a first-in-class, oral exportin 1 (XPO1) inhibitor compound"

A XPO1 inhibitor is a type of drug that blocks the protein exportin 1 (XPO1), which normally transports important regulatory molecules out of a cell’s nucleus. By trapping tumor-suppressing proteins inside the nucleus, these drugs can disrupt cancer cell survival and growth; think of it as preventing a courier from carrying critical tools out of a workshop. Investors track XPO1 inhibitors because their clinical trial results, regulatory approvals, safety profile, and patent positions drive potential market value and commercial prospects.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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– sNDA Submitted under the Accelerated Approval Pathway; Priority Review Requested –

NEWTON, Mass., Aug. 31, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) seeking Accelerated Approval for XPOVIO® (selinexor) in combination with ruxolitinib for patients with myelofibrosis. Karyopharm requested Priority Review of the application, which, if granted, could result in a six-month review process.

"Today's submission is an important step toward our goal of bringing the combination of selinexor plus ruxolitinib to patients with myelofibrosis who continue to face a significant unmet need," said Reshma Rangwala, M.D., Ph.D., Chief Medical Officer and Head of Research of Karyopharm. "The SENTRY trial generated compelling and consistent results, including rapid, deep and sustained spleen responses across a broad range of patients, together with a promising overall survival signal and important evidence of disease modification. We believe the strength of these data underscores the potential of this novel combination to deliver meaningful long-term benefits and fundamentally change the treatment of patients with myelofibrosis."

Following the topline results of the Phase 3 SENTRY trial, the Company has engaged productively with the FDA. The sNDA submitted is based, in part, on data from the SENTRY trial that the Company believes supports a positive benefit-risk profile for the combination, including a promising signal of overall survival. The Company expects approval under the Accelerated Approval pathway would require the FDA to agree that spleen volume reduction ≥ 35% (SVR35) is a reasonably likely surrogate endpoint to predict overall survival. The Company plans to use long-term overall survival data from the Phase 3 SENTRY trial to verify clinical benefit and support conversion from accelerated to traditional approval and expects to continue working with the FDA during its review of the sNDA to finalize the confirmatory evidence plan. Karyopharm expects to receive notice of the FDA's decision on sNDA filing acceptance and, if accepted, the anticipated review timelines in the fourth quarter of 2026, following the FDA's 60-day filing review period. 

In May 2022, the FDA granted selinexor Orphan Drug Designation for the treatment of myelofibrosis, and in October 2022, the European Commission granted Orphan Medicinal Product Designation for selinexor for the treatment of myelofibrosis. In addition, in July 2023, the Company received Fast Track Designation from the FDA for selinexor for the treatment of patients with myelofibrosis, including primary myelofibrosis, post-essential thrombocythemia myelofibrosis, and post-polycythemia vera myelofibrosis.

About the Phase 3 SENTRY Trial

SENTRY (XPORT-MF-034; NCT04562389) is a Phase 3 clinical trial evaluating a once-weekly dose of 60 mg of selinexor in combination with ruxolitinib compared to placebo plus ruxolitinib in JAKi-naïve myelofibrosis patients with platelet counts >100 x 10⁹/L (N=353). Patients were randomized 2-to-1 to the selinexor arm. The co-primary endpoints for this trial are spleen volume reduction ≥ 35% (SVR35) at week 24 and the average change in absolute total symptom score (Abs-TSS) over 24 weeks relative to baseline. The results from the Phase 3 SENTRY trial were presented at the 2026 American Society of Clinical Oncology Annual Meeting and were simultaneously published in the peer-reviewed Journal of Clinical Oncology. In addition, the results were presented at the 2026 European Hematology Association Congress, where the presentation was recognized as one of the six best abstracts at the meeting.

About Myelofibrosis

Myelofibrosis is a rare blood cancer that affects approximately 20,000 patients in the United States and 19,000 patients in the European Union¹. The disease causes bone marrow fibrosis (scarring in the bone marrow), which makes it difficult for the bone marrow to make healthy blood cells, splenomegaly (enlarged spleen), progressive anemia which often leads to symptoms like fatigue and weakness, and other disease associated symptoms including abdominal discomfort, pain under the left ribs, early satiety, night sweats and bone pain. The only approved class of therapies to treat myelofibrosis are JAK inhibitors, including ruxolitinib.

1. Clarivate/DRG (2023)

About XPOVIO® (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor compound for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved and marketed by Karyopharm in the U.S. in multiple oncology indications, including: (i) in combination with VELCADE® (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma after at least one prior therapy; and (ii) in combination with dexamethasone in adult patients with heavily pre-treated multiple myeloma. 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, Mainland China, Taiwan, Hong Kong, Australia, South Korea, Singapore, Israel, and Canada. XPOVIO®/NEXPOVIO® is marketed in these respective ex-U.S. territories by Karyopharm's partners: Antengene, Menarini, Neopharm, and FORUS. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high-unmet need cancer indications.

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).

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%.

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 is a commercial-stage pharmaceutical company pioneering the science of nuclear export inhibition to develop differentiated therapies for patients with cancer. The Company's lead therapy, XPOVIO® (selinexor), is a first-in-class inhibitor of exportin 1 (XPO1). XPOVIO is marketed by the Company in the U.S. for adults with relapsed or refractory multiple myeloma and is approved as XPOVIO or NEXPOVIO® in more than 50 ex-U.S. countries and territories. Building on its leadership in XPO1 biology, Karyopharm is advancing selinexor's potential in hematological cancers, including in myelofibrosis. The Company is also exploring opportunities to evaluate XPO1 inhibition across myeloproliferative neoplasms using next-generation compounds, including eltanexor. Headquartered in Newton, Massachusetts, Karyopharm has an established, efficient, and scalable commercial infrastructure to bring novel therapeutic options to patients with cancer. For more information, visit www.karyopharm.com and follow Karyopharm on LinkedIn and on X at @Karyopharm.

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 with respect to the FDA's review timing and the completeness and acceptability of its sNDA submission for selinexor in combination with ruxolitinib in myelofibrosis; Karyopharm's ongoing engagement with the FDA; the potential availability of the accelerated approval pathway; whether long-term overall survival data from the SENTRY trial will verify clinical benefit; the potential availability of priority review of the sNDA; expectations with respect to commercialization efforts; and the ability of selinexor and eltanexor to treat patients with multiple myeloma, myelofibrosis, and other diseases. 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, 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 trials, including subsequent analysis of existing data and new data received from ongoing and future trials; 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 trials; 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; substantial doubt exists regarding Karyopharm's ability to continue as a going concern; 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 June 30, 2026, which was filed with the Securities and Exchange Commission (SEC) on August 13, 2026, 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.

CONTACT:

Brendan Strong
Senior Vice President, Investor Relations
617.762.2661
brendan.strong@karyopharm.com

 

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SOURCE Karyopharm Therapeutics Inc.

FAQ

What did Karyopharm (KPTI) announce about XPOVIO and ruxolitinib for myelofibrosis on August 31, 2026?

Karyopharm announced submission of a supplemental New Drug Application to the FDA seeking Accelerated Approval of XPOVIO plus ruxolitinib for myelofibrosis. According to Karyopharm, the application is supported by Phase 3 SENTRY trial data in JAK inhibitor–naïve myelofibrosis patients.

Is Karyopharm’s sNDA for XPOVIO plus ruxolitinib in myelofibrosis under Priority Review by the FDA?

Karyopharm has requested Priority Review for the sNDA, but it has not yet been granted. According to Karyopharm, if Priority Review is approved, the FDA’s review period could be approximately six months instead of the standard timeline.

What clinical trial data support Karyopharm’s myelofibrosis sNDA for XPOVIO (KPTI)?

The sNDA is supported in part by the Phase 3 SENTRY trial in 353 JAK inhibitor–naïve myelofibrosis patients. According to Karyopharm, SENTRY evaluated selinexor plus ruxolitinib versus placebo plus ruxolitinib, with co‑primary endpoints of SVR35 at week 24 and symptom score change.

When does Karyopharm expect FDA feedback on the XPOVIO myelofibrosis sNDA (KPTI)?

Karyopharm expects to receive the FDA’s decision on sNDA filing acceptance and review timelines in the fourth quarter of 2026. According to Karyopharm, this timing follows the FDA’s standard 60‑day filing review period for new submissions.

What regulatory designations does selinexor have for myelofibrosis that may affect KPTI investors?

Selinexor has U.S. Orphan Drug and Fast Track designations for myelofibrosis and EU Orphan Medicinal Product designation. According to Karyopharm, these designations recognize the rare, serious nature of myelofibrosis and may offer regulatory and development incentives.

What endpoints are key for the potential accelerated approval of XPOVIO plus ruxolitinib in myelofibrosis?

The company expects accelerated approval would require FDA agreement that SVR35 is a reasonably likely surrogate for overall survival. According to Karyopharm, long‑term overall survival data from the SENTRY trial are planned as confirmatory evidence for potential traditional approval.

Is XPOVIO already approved for any indications relevant to Karyopharm (KPTI) shareholders?

Yes. XPOVIO is approved in the U.S. for adult patients with multiple myeloma in specified combination regimens. According to Karyopharm, XPOVIO or NEXPOVIO is also approved in multiple ex‑U.S. territories across various oncology indications, supporting an established commercial base.