Karyopharm Plans to Submit sNDA for Selinexor Plus Ruxolitinib in Myelofibrosis Under Accelerated Approval Pathway

Rhea-AI Summary

Karyopharm Therapeutics (Nasdaq: KPTI) plans to submit a supplemental New Drug Application (sNDA) to the U.S. FDA in August 2026 seeking accelerated approval of selinexor plus ruxolitinib for patients with myelofibrosis and will request Priority Review.

According to Karyopharm, recent FDA feedback indicated spleen volume reduction ≥35% (SVR35) appears to qualify as a reasonably likely surrogate endpoint to support use of the accelerated approval pathway. The sNDA will rely on Phase 3 SENTRY topline data, including statistically significant SVR35 at week 24, a promising overall survival signal, reductions in variant allele frequency, and the overall safety dataset. Long-term overall survival from the ongoing SENTRY trial, which randomized 353 JAK inhibitor–naïve myelofibrosis patients 2:1 to selinexor plus ruxolitinib versus placebo plus ruxolitinib, is planned to verify clinical benefit.

Positive

• Accelerated approval sNDA planned for selinexor plus ruxolitinib in myelofibrosis in August 2026
• Priority Review to be requested, potentially shortening FDA review to about six months after acceptance
• Phase 3 SENTRY showed statistically significant SVR35 improvement at week 24 in 353 randomized patients
• SVR35 accepted as RLSE by FDA in written feedback to support use of accelerated approval pathway

Negative

• None.

News Explained

Karyopharm has not yet filed the sNDA: it plans to submit in August 2026 and request Priority Review; if FDA grants that request, the target action date would be approximately six months after FDA receives the application.

Market reaction after August 2026 sNDA submission: KPTI -72.61% in the Jul 31 session

-72.61% 27.9x vol

66 alerts

-72.61% Session close to close

-72.7% Trough in 27 hr 11 min

$154.24M Market Cap

27.9x Rel. Volume

In the Jul 31 session, KPTI declined 72.61%, reflecting a significant negative market reaction. Argus tracked a trough of -72.7% from its starting point during tracking. Our momentum scanner triggered 66 alerts that day, indicating high trading interest and price volatility. Trading volume was exceptionally heavy at 27.9x the daily average, suggesting significant selling pressure.

Data tracked by StockTitan Argus on the day of publication.

Market Context

The stock dropped -72.6% in the session following this news. The prior SENTRY disclosures were follo...

Analysis

The stock dropped -72.6% in the session following this news. The prior SENTRY disclosures were followed by a -6.01% 24-hour reaction. The August sNDA plan still requires accelerated approval and later clinical-benefit verification; the active S-3 registers resale shares, not company proceeds, while high short positioning is a risk.

Key Figures

Planned sNDA submission: August 2026 SVR35 threshold: ≥35% PDUFA target timing: 6 months +5 more

8 metrics

Planned sNDA submission August 2026 Selinexor plus ruxolitinib in myelofibrosis

SVR35 threshold ≥35% Spleen volume reduction endpoint

PDUFA target timing 6 months Following FDA receipt if Priority Review is granted

Trial phase Phase 3 Ongoing SENTRY trial

Dose 60 mg Once-weekly selinexor dose in SENTRY

Sample size 353 patients JAK inhibitor-naive myelofibrosis patients

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

Platelet-count criterion >100 x 109/L SENTRY eligibility criterion

Historical Context

5 past events · Latest: Jul 01 (Neutral)

Pattern 5 events

Date	Event	Sentiment	24h Move	Catalyst
Jul 01	Inducement grants	Neutral	+0.5%	RSU grants to four newly hired employees under Nasdaq inducement provisions
Jun 03	Investor webcast	Neutral	+0.8%	Company announced a management webcast featuring an endometrial cancer trial investigator
Jun 02	Clinical trial presentation	Positive	-6.0%	SENTRY data selected for late-breaking oral presentation at EHA 2026
Jun 02	Phase 3 clinical data	Positive	-6.0%	SENTRY results showed significant SVR35 improvement and favorable overall survival hazard ratio
Jun 01	Inducement grant	Neutral	-6.0%	Company granted restricted stock units to a newly hired employee

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

Pattern Detected

KPTI's prior positive SENTRY-related announcements were followed by negative 24-hour reactions of -6.01%, while routine corporate notices showed smaller moves.

Key Terms

snda, accelerated approval, reasonably likely surrogate endpoint, pdufa, +1 more

5 terms

snda regulatory

"plans to submit a supplemental New Drug Application (sNDA)"

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

"support an sNDA under the accelerated approval pathway"

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.

reasonably likely surrogate endpoint regulatory

"qualify as a reasonably likely surrogate endpoint (RLSE)"

A reasonably likely surrogate endpoint is a measurable biological sign or test result that regulators accept as likely to predict a real patient benefit, even if the actual clinical outcome (like longer survival or fewer symptoms) has not yet been proven. Think of it like a car’s dashboard warning light that is a reliable sign the engine problem will affect performance; for investors, it signals faster regulatory paths and earlier market access while final proof is still pending.

pdufa regulatory

"a Prescription Drug User Fee Act (PDUFA) target action date"

PDUFA is the Prescription Drug User Fee Act, the U.S. law under which drug companies pay fees that fund the FDA's review of new medicines. In company news the term usually appears as the PDUFA date, the target deadline by which the FDA aims to decide on a drug application; that date tells investors when to expect the approval or rejection decision for the product.

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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– Company Plans to Submit sNDA in August 2026 and Will Request Priority Review –

– Following FDA Engagements, Company Plans to Submit sNDA under Accelerated Approval Based Upon Compelling SVR35 Data and Preliminary Overall Survival Data Observed at the Time of the Topline Results –

– Company Plans to Use Long-Term Overall Survival Data from the Ongoing Phase 3 SENTRY Trial to Verify Clinical Benefit –

– If Approved, Selinexor in Combination with Ruxolitinib has the Potential to Become the First Approved Combination Therapy for Patients with Myelofibrosis, Adding a Novel Class of Therapy –

NEWTON, Mass., July 30, 2026 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced that it plans to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) in August 2026 seeking accelerated approval of selinexor in combination with ruxolitinib for the treatment of patients with myelofibrosis.

The planned submission follows productive engagements with the FDA, including written feedback that spleen volume reduction ≥ 35% (SVR35) appears to qualify as a reasonably likely surrogate endpoint (RLSE) to predict overall survival and can be used to support an sNDA under the accelerated approval pathway. The Company plans to use overall survival data from long-term follow-up of the ongoing Phase 3 SENTRY trial to verify clinical benefit. Overall survival is a pre-specified secondary endpoint of SENTRY. The trial does not permit patient crossover; patients, investigators and the Karyopharm study team remain blinded to treatment assignment during ongoing follow-up.

"The SENTRY trial generated one of the most compelling frontline datasets in myelofibrosis to date," said Dr. John Mascarenhas, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Center of Excellence for Blood Cancers and Myeloid Disorders. "The combination of selinexor and ruxolitinib demonstrated compelling spleen responses across a broad range of subgroups. The spleen responses were rapid, deep and sustained with promising overall survival findings and important evidence of disease modification. These results have the potential to redefine frontline treatment and establish a new treatment paradigm for patients with myelofibrosis."

"Patients with myelofibrosis have waited too long for meaningful innovation," said Richard Paulson, President and Chief Executive Officer of Karyopharm. "We are grateful to the FDA for its thoughtful and collaborative engagement in helping define a rigorous path forward. If approved, selinexor in combination with ruxolitinib has the potential to become the first approved combination therapy for patients with myelofibrosis, incorporating a novel class of therapy. We believe this represents a potentially transformative opportunity for patients and a defining moment in Karyopharm's history as we work with urgency toward our planned August sNDA submission."

The planned sNDA will be based on results from the randomized, double-blind, Phase 3 SENTRY trial that compared selinexor in combination with ruxolitinib against placebo in combination with ruxolitinib, including the statistically significant improvement in SVR35 at week 24, the rapid, deep and sustained nature of the spleen responses, a promising overall survival signal, reductions in variant allele frequency and the overall safety data package.

"The SENTRY trial generated a substantial body of evidence showing consistent improvements across multiple measures of clinical activity, including spleen response and a promising signal of overall survival," said Reshma Rangwala, M.D., Ph.D., Chief Medical Officer and Head of Research of Karyopharm. "Together, these findings reinforce the biologic rationale for combining XPO1 and JAK inhibition and support the potential of this novel combination to deliver meaningful long-term benefits for patients with myelofibrosis."

Karyopharm intends to request Priority Review at the time of submission of the sNDA, which, if granted, would result in a Prescription Drug User Fee Act (PDUFA) target action date approximately six months following the FDA's receipt of the application.

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 17,000 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 timing and submission of a potential sNDA 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; and the potential for selinexor to treat patients with 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 March 31, 2026, which was filed with the Securities and Exchange Commission (SEC) on May 14, 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.

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SOURCE Karyopharm Therapeutics Inc.

FAQ

What did Karyopharm (NASDAQ: KPTI) announce on July 30, 2026 about selinexor plus ruxolitinib in myelofibrosis?

Karyopharm announced plans to file an sNDA in August 2026 seeking FDA accelerated approval for selinexor plus ruxolitinib in myelofibrosis. According to Karyopharm, the filing will be based on Phase 3 SENTRY data, including statistically significant SVR35 improvement and a promising overall survival signal.

When will Karyopharm (KPTI) submit the sNDA for selinexor plus ruxolitinib and what review timeline is expected?

Karyopharm plans to submit the sNDA in August 2026 and will request Priority Review. According to Karyopharm, if Priority Review is granted, the Prescription Drug User Fee Act (PDUFA) target action date would be approximately six months after the FDA receives and accepts the application.

What is SVR35 and why is it important for Karyopharm’s (KPTI) selinexor sNDA in myelofibrosis?

SVR35 is spleen volume reduction of at least 35%, a key efficacy measure in myelofibrosis. According to Karyopharm, FDA written feedback indicated SVR35 appears to qualify as a reasonably likely surrogate endpoint to predict overall survival and can support use of the accelerated approval pathway.

What is the Phase 3 SENTRY trial supporting Karyopharm (KPTI) selinexor plus ruxolitinib in myelofibrosis?

SENTRY is a randomized, double-blind Phase 3 trial in 353 JAK inhibitor–naïve myelofibrosis patients with platelets above 100×10⁹/L. According to Karyopharm, patients were randomized 2:1 to selinexor plus ruxolitinib versus placebo plus ruxolitinib, with co-primary endpoints including SVR35 and symptom score change.

How will long-term overall survival data from SENTRY be used for Karyopharm (KPTI) selinexor in myelofibrosis?

Long-term overall survival data from the ongoing SENTRY trial are planned to verify clinical benefit after any accelerated approval. According to Karyopharm, overall survival is a pre-specified secondary endpoint, and the trial does not permit patient crossover during blinded follow-up.

Could selinexor plus ruxolitinib become the first approved combination therapy for myelofibrosis if KPTI gains FDA approval?

If the sNDA is approved, selinexor plus ruxolitinib could become the first approved combination regimen for myelofibrosis. According to Karyopharm, this would add a novel XPO1 inhibitor class alongside existing JAK inhibitor therapy for eligible myelofibrosis patients in the United States.