Syndax’s Revuforj® (revumenib) Included in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the Treatment of Relapsed or Refractory NPM1 Mutated Acute Myeloid Leukemia

Rhea-AI Summary

Syndax Pharmaceuticals (NASDAQ:SNDX) announced that its drug Revuforj® (revumenib) has been included in the NCCN Guidelines® as a category 2A treatment recommendation for relapsed or refractory NPM1 mutated acute myeloid leukemia (AML). The update follows positive results from the AUGMENT-101 trial published in Blood in 2025.

The drug maintains its category 2A recommendation for R/R acute leukemia with KMT2A rearrangement. Syndax has submitted a supplemental New Drug Application (sNDA) for revumenib with Priority Review status and a PDUFA date of October 25, 2025.

Positive

• NCCN Guidelines inclusion strengthens revumenib's market position
• FDA granted Priority Review status for the sNDA
• Positive clinical trial results published in prestigious journal Blood
• Drug received category 2A recommendation for two indications

Negative

• None.

Insights

Oncology and Hematology Specialist

NCCN guideline inclusion for Revuforj in NPM1-mutated AML strengthens Syndax's market position ahead of FDA's October decision.

The inclusion of revumenib (Revuforj®) in the prestigious NCCN Guidelines represents a significant clinical validation for Syndax Pharmaceuticals. NCCN guidelines serve as the gold standard for clinical decision-making in oncology, directly influencing treatment protocols at major cancer centers nationwide. This Category 2A recommendation—indicating uniform consensus that the intervention is appropriate—for NPM1-mutated relapsed/refractory AML significantly expands revumenib's addressable patient population beyond its existing recommendation for KMT2A-rearranged leukemias.

The timing is particularly strategic with the FDA's Priority Review decision expected by October 25, 2025. Priority Review designations are reserved for drugs that would significantly improve treatment of serious conditions, suggesting regulatory confidence in revumenib's clinical profile. The AUGMENT-101 trial results published in Blood likely demonstrated compelling efficacy in a difficult-to-treat population where therapeutic options remain limited.

NPM1 mutations occur in approximately 30% of AML cases, representing a substantial market opportunity. Guideline inclusion critically facilitates reimbursement pathways, as both private and public payers heavily reference NCCN recommendations when establishing coverage policies. For hematologic malignancies like AML, where treatment costs frequently exceed $200,000 annually, securing favorable reimbursement positioning through NCCN inclusion substantially de-risks the commercial outlook.

This development positions Syndax advantageously in the competitive landscape for targeted AML therapies, potentially accelerating clinical adoption once the expected label expansion receives FDA approval next month.

NEW YORK, Sept. 19, 2025 (GLOBE NEWSWIRE) -- Syndax Pharmaceuticals (Nasdaq: SNDX), a commercial-stage biopharmaceutical company advancing innovative cancer therapies, today announced that the National Comprehensive Cancer Network^® (NCCN^®) Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Acute Myeloid Leukemia were updated to include revumenib as a category 2A recommendation for relapsed or refractory (R/R) acute myeloid leukemia (AML) with an NPM1 mutation (mNPM1).¹ The update was based on positive pivotal results from the AUGMENT-101 trial of revumenib which were published in the journal Blood in 2025.² The NCCN Guidelines for AML and acute lymphoblastic leukemia (ALL) continue to also include revumenib as a category 2A recommendation for R/R acute leukemia with a KMT2A rearrangement.

“The inclusion of revumenib as a recommended treatment option for R/R NPM1 mutated AML in the NCCN Guidelines underscores the strength of our clinical data in this population and further solidifies revumenib’s leading position,” said Nick Botwood, MBBS, Head of Research & Development and Chief Medical Officer at Syndax. “Given the pivotal role NCCN Guidelines play in guiding the decision-making process for clinicians, payers, patients, and other key stakeholders in the U.S. and beyond, this is a major milestone for Syndax and the entire acute leukemia community.”

The Company has submitted a supplemental New Drug Application (sNDA) seeking the approval of revumenib for the treatment of R/R mNPM1 AML. The sNDA has been granted Priority Review by the FDA and assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 25, 2025.

The NCCN is a not-for-profit alliance of 33 leading cancer centers devoted to patient care, research, and education. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system.

About Mutant NPM1 (mNPM1) Acute Myeloid Leukemia (AML)

Mutations in the NPM1 gene are the most common genetic alteration observed in AML, occurring in approximately 30% of adults with AML. Mutations in this gene play a critical role in the development of mutant NPM1 (mNPM1) AML, an aggressive blood cancer associated with high rates of relapse. Patients with relapsed or refractory mNPM1 AML have a poor prognosis and critical unmet need. Similar to KMT2A-rearranged acute leukemia, mNPM1 AML is highly dependent on the menin-KMT2A interaction and disruption of this interaction has been shown to lead to downregulation of certain leukemogenic genes. mNPM1 AML is routinely diagnosed through currently available screening techniques. There are currently no approved therapies that selectively target the underlying disease mechanisms driving mNPM1 AML.

About Revuforj^® (revumenib)

Revuforj (revumenib) is an oral, first-in-class menin inhibitor that is FDA approved for the treatment of relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients one year and older.

The FDA has granted Priority Review to Syndax’s supplemental New Drug Application (sNDA) seeking the approval of revumenib for the treatment of R/R mNPM1 AML. The sNDA is being reviewed under the FDA's Real-Time Oncology Review (RTOR) program, which allows for a more efficient review and close engagement between the sponsor and FDA. The sNDA is supported by positive pivotal data from the AUGMENT-101 trial of revumenib in patients with R/R mNPM1 AML. Results from this population were published in the journal Blood and presented at the 2025 European Hematology Association (EHA) Annual Congress Meeting.

Additionally, multiple trials of revumenib are ongoing or planned across the treatment landscape, including in combination with standard of care therapies in newly diagnosed patients with mNPM1 or KMT2Ar AML.

Revumenib was previously granted Orphan Drug Designation for the treatment of AML, ALL and acute leukemias of ambiguous lineage (ALAL) by the U.S. FDA and for the treatment of AML by the European Commission. The U.S. FDA also granted Fast Track designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemias harboring a KMT2A rearrangement or NPM1 mutation and Breakthrough Therapy Designation for the treatment of adult and pediatric patients with R/R acute leukemia harboring a KMT2A rearrangement.

IMPORTANT SAFETY INFORMATION

WARNING: DIFFERENTIATION SYNDROME

Differentiation syndrome, which can be fatal, has occurred with Revuforj. Signs and symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, and renal dysfunction. If differentiation syndrome is suspected, immediately initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.

WARNINGS AND PRECAUTIONS

Differentiation syndrome: Revuforj can cause fatal or life-threatening differentiation syndrome (DS). Symptoms of DS, including those seen in patients treated with Revuforj, include fever, dyspnea, hypoxia, peripheral edema, pleuropericardial effusion, acute renal failure, and/or hypotension. In clinical trials, DS occurred in 39 (29%) of 135 patients treated with Revuforj. DS was Grade 3 or 4 in 13% of patients and fatal in one. The median time to onset was 10 days (range 3-41 days). Some patients experienced more than 1 DS event. Treatment interruption was required for 7% of patients, and treatment was withdrawn for 1%.

Reduce the white blood cell count to less than 25 Gi/L prior to starting Revuforj. If DS is suspected, immediately initiate treatment with systemic corticosteroids (e.g., dexamethasone 10-mg IV every 12 hours in adults or dexamethasone 0.25-mg/kg/dose IV every 12 hours in pediatric patients weighing less than 40 kg) for a minimum of 3 days and until resolution of signs and symptoms. Institute supportive measures and hemodynamic monitoring until improvement. Interrupt Revuforj if severe signs and/or symptoms persist for more than 48 hours after initiation of systemic corticosteroids, or earlier if life-threatening symptoms occur such as pulmonary symptoms requiring ventilator support. Restart steroids promptly if DS recurs after tapering corticosteroids.

QTc interval prolongation: In the clinical trials, QTc interval prolongation was reported as an adverse reaction in 39 (29%) of 135 patients treated with Revuforj. QTc interval prolongation was Grade 3 in 12% of patients. The heart-rate corrected QT interval (using Fridericia’s method) (QTcF) was greater than 500 msec in 8%, and the increase from baseline QTcF was greater than 60 msec in 18%. Revuforj dose reduction was required for 5% of patients due to QTc interval prolongation. QTc prolongation occurred in 16% of the 31 patients less than 17 years old, 33% of the 88 patients 17 years to less than 65 years old, and in 50% of the 16 patients 65 years or older.

Correct electrolyte abnormalities, including hypokalemia and hypomagnesemia, prior to treatment with Revuforj. Perform an electrocardiogram (ECG) prior to initiation of Revuforj, and do not initiate Revuforj in patients with QTcF >450 msec. Perform an ECG at least once weekly for the first 4 weeks and at least monthly thereafter. In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary. Concomitant use with drugs known to prolong the QTc interval may increase the risk of QTc interval prolongation.

• Interrupt Revuforj if QTcF increases >480 msec and <500 msec, and restart Revuforj at the same dose twice daily after the QTcF interval returns to ≤480 msec
• Interrupt Revuforj if QTcF increases >500 msec or by >60 msec from baseline, and restart Revuforj twice daily at the lower-dose level after the QTcF interval returns to ≤480 msec
• Permanently discontinue Revuforj in patients with ventricular arrhythmias and in those who develop QTc interval prolongation with signs or symptoms of life-threatening arrhythmia.
  

Embryo-fetal toxicity: Revuforj 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 female partners of reproductive potential to use effective contraception during treatment with Revuforj and for 4 months after the last dose of Revuforj.

ADVERSE REACTIONS

Fatal adverse reactions occurred in 4 (3%) patients who received Revuforj, including 2 with differentiation syndrome, 1 with hemorrhage, and 1 with sudden death.

Serious adverse reactions were reported in 99 (73%) patients. The most frequent serious adverse reactions (≥5%) were infection (24%), febrile neutropenia (19%), bacterial infection (17%), differentiation syndrome (12%), hemorrhage (9%), and thrombosis (5%).

The most common adverse reactions (≥20%) including laboratory abnormalities, were hemorrhage (53%), nausea (51%), phosphate increased (50%), musculoskeletal pain (42%), infection (41%), aspartate aminotransferase increased (37%), febrile neutropenia (35%), alanine aminotransferase increased (33%), parathyroid hormone intact increased (33%), bacterial infection (31%), diarrhea (30%), differentiation syndrome (29%), electrocardiogram QT prolonged (29%), phosphate decreased (25%), triglycerides increased (25%), potassium decreased (24%), decreased appetite (24%), constipation (23%), edema (23%), viral infection (23%), fatigue (22%), and alkaline phosphatase increased (21%).

DRUG INTERACTIONS

Drug interactions can occur when Revuforj is concomitantly used with:

• Strong CYP3A4 inhibitors: reduce Revuforj dose
• Strong or moderate CYP3A4 inducers: avoid concomitant use with Revuforj
• QTc-prolonging drugs: avoid concomitant use with Revuforj. If concomitant use is unavoidable, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold Revuforj if the QTc interval is >480 msec. Restart Revuforj after the QTc interval returns to ≤480 msec.
  

SPECIFIC POPULATIONS

Lactation: advise lactating women not to breastfeed during treatment with Revuforj and for 1 week after the last dose.

Pregnancy and testing: Revuforj can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential within 7 days prior to initiating Revuforj.

Pediatric: monitor bone growth and development in pediatric patients.

Geriatric: compared to younger patients, the incidences of QTc prolongation and edema were higher in patients 65 years and older.

Infertility: based on findings in animals, Revuforj may impair fertility. The effects on fertility were reversible.

To report SUSPECTED ADVERSE REACTIONS, contact Syndax Pharmaceuticals at 1-888-539-3REV or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see Full Prescribing Information, including BOXED WARNING.

About the Real-Time Oncology Review (RTOR) Program

RTOR provides a more efficient review process for oncology drugs to ensure that safe and effective treatments are available to patients as early as possible, while improving review quality and engaging in early iterative communication with the applicant. Specifically, it allows for close engagement between the sponsor and the FDA throughout the submission process and it enables the FDA to review individual sections of modules of a drug application rather than requiring the submission of complete modules or a complete application prior to initiating review. Additional information about RTOR can be found at: https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review.

About Syndax

Syndax Pharmaceuticals is a commercial-stage biopharmaceutical company advancing innovative cancer therapies. Highlights of the Company's pipeline include Revuforj^® (revumenib), an FDA-approved menin inhibitor, and Niktimvo™ (axatilimab-csfr), an FDA-approved monoclonal antibody that blocks the colony stimulating factor 1 (CSF-1) receptor. Fueled by our commitment to reimagining cancer care, Syndax is working to unlock the full potential of its pipeline and is conducting several clinical trials across the continuum of treatment. For more information, please visit www.syndax.com/ or follow the Company on X and LinkedIn.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipate," "believe," "could," "estimate," "expects," "intend," "may," "plan," "potential," "predict," "project," "should," "will," "would" or the negative or plural of those terms, and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances) are intended to identify forward-looking statements. These forward-looking statements are based on Syndax's expectations and assumptions as of the date of this press release. Each of these forward-looking statements involves risks and uncertainties. Actual results may differ materially from these forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about the progress, timing, clinical development and scope of clinical trials, the reporting of clinical data for Syndax's product candidates, the acceptance of Syndax and its partners' products in the marketplace, sales, marketing, manufacturing and distribution requirements, and the potential use of its product candidates to treat various cancer indications and fibrotic diseases. Many factors may cause differences between current expectations and actual results, including: unexpected safety or efficacy data observed during preclinical or clinical trials; clinical trial site activation or enrollment rates that are lower than expected; changes to Revuforj's or Niktimvo’s commercial availability; changes in expected or existing competition; changes in the regulatory environment; failure of Syndax's collaborators to support or advance collaborations or product candidates; and unexpected litigation or other disputes. Other factors that may cause Syndax's actual results to differ from those expressed or implied in the forward-looking statements in this press release are discussed in Syndax's filings with the U.S. Securities and Exchange Commission, including the "Risk Factors" sections contained therein. Except as required by law, Syndax assumes no obligation to update any forward-looking statements contained herein to reflect any change in expectations, even as new information becomes available.

Niktimvo is a trademark of Incyte.
All other trademarks are the property of their respective owners.

References

1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Acute Myeloid Leukemia (Version 1.2026 – September 18, 2025); NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
2. Martha L. Arellano, et al. Menin inhibition with revumenib for NPM1-mutated relapsed or refractory acute myeloid leukemia: the AUGMENT-101 study. Blood 2025. https://doi.org/10.1182/blood.2025028357

Syndax Contact:

Sharon Klahre
Syndax Pharmaceuticals, Inc.
sklahre@syndax.com
Tel 781.684.9827

SNDX-G

FAQ

What is the significance of Revuforj's inclusion in NCCN Guidelines for AML treatment?

The inclusion as a category 2A recommendation validates the drug's clinical effectiveness for treating relapsed or refractory NPM1 mutated AML, making it a recognized treatment option for healthcare providers and payers.

When is the FDA expected to decide on Syndax's sNDA for Revuforj?

The FDA has set a PDUFA target action date of October 25, 2025 for the supplemental New Drug Application of Revuforj.

What indications is Revuforj (SNDX) recommended for in the NCCN Guidelines?

Revuforj is recommended for two indications: relapsed or refractory NPM1 mutated AML and R/R acute leukemia with KMT2A rearrangement.

What clinical trial supported Revuforj's inclusion in the NCCN Guidelines?

The AUGMENT-101 trial provided the positive pivotal results that supported Revuforj's inclusion, with results published in the journal Blood in 2025.

What type of review status did the FDA grant to Syndax's sNDA for Revuforj?

The FDA granted Priority Review status to the supplemental New Drug Application for Revuforj.