The U.S. Food and Drug Administration (FDA) has approved Revuforj (revumenib), which is a menin inhibitor, for the treatment of relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation in adult and pediatric patients 1 year old and older who have no satisfactory alternative treatment options.
The approval was announced in a news release issued by the agency.
The drug’s effectiveness was determined in a single-arm cohort of the open-label, multicenter SNDX-5613-0700, or AUGMENT-101, clinical trial, in which a susceptible mutation was confirmed in enrolled patients using next-generation sequencing or polymerase chain reaction of the last exon of NPM1.
Glossary
Complete Remission Rate (CR): the percentage of patients whose cancer can no longer be detected after treatment.
Complete Remission with Partial Hematological Recovery (CRh): cancer is no longer detectable (complete remission), but the blood counts — such as red cells, white cells, or platelets — have not fully returned to normal levels.
Transfusion Dependence: when a person needs regular blood transfusions (red cells or platelets) because their body cannot make enough healthy blood cells on its own.
Differentiation Syndrome: A possible side effect of some cancer treatments that cause immature cancer cells to mature (or “differentiate”) quickly. This sudden change can lead to symptoms such as fever, weight gain, fluid buildup, or breathing problems.
QTc Interval Prolongation and Torsades de Pointes: These terms refer to changes in the heart’s electrical activity that can be seen on an electrocardiogram (ECG). QTc prolongation means the heart takes slightly longer than normal to recharge between beats. Torsades de Pointes is a rare but serious type of abnormal heart rhythm that can occur if the QTc becomes too long.
Embryo-Fetal Toxicity: Some medicines can harm an unborn baby if taken during pregnancy. This is called embryo-fetal toxicity.
The main outcomes of the trial were complete remission rate (CR), complete remission with partial hematological recovery (CRh), CR and CRh duration and the rate of conversion from transfusion dependence to transfusion independence.
The agency reported that the CR+CRh rate was 23.1% and the median CR+CRh duration was 4.5 months, and of the 46 patients who were dependent on red blood cell (RBC) and/or platelet transfusions at baseline, eight (17%) became independent of RBC and platelet transfusions during any 56-day post-baseline period.
Regarding safety, the agency noted that the drug’s prescribing information includes warnings and precautions for differentiation syndrome, QTc interval prolongation and Torsades de Pointes, and embryo-fetal toxicity.
The recommended dosage of Revuforj, the agency stated, varies by a patient’s weight and concomitant use of strong CYP3A4 inhibitors.
What is Revuforj and How Does It Work to Treat AML?
Revuforj, as defined by the National Cancer Institute on its website, is a drug that binds to a protein called menin and keeps it from binding to another protein called KMT2A, and this in turn stops or slows the growth of leukemia cells with changes in the KMT2A gene.
It was previously approved by the FDA in November 2024 for the treatment of adults and children aged 1 year and older with relapsed or refractory acute leukemia with a KMT2A translocation.
The oral drug was granted priority review by the FDA in June 2025 for the treatment of relapsed or refractory mutant NPM1-positive AML, according to a news release from Syndax Pharmaceuticals, the manufacturer of the drug.
Syndax announced in September that the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML were updated to include Revuforj as a category 2A recommendation for relapsed or refractory (R/R) acute myeloid leukemia (AML) with an NPM1 mutation (mNPM1), with the update based on positive pivotal results from the AUGMENT-101 trial of revumenib which were published in the journal Blood earlier this year.
“The inclusion of [Revuforj] as a recommended treatment option for R/R NPM-mutated AML in the NCCN Guidelines underscores the strength of our clinical data in this population and further solidifies [Revuforj’s] leading position,” said Nick Botwood, head of research and development and chief medical officer at Syndax, in a news release issued at the time. “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.”
Syndax has stated that additionally, multiple trials of Revuforj 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.
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References:
- “FDA approves revumenib for relapsed or refractory acute myeloid leukemia with a susceptible NPM1 mutation,” FDA; https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-myeloid-leukemia-susceptible-npm1-mutation?utm_medium=email&utm_source=govdelivery
- “Revuforj,” National Cancer Institute; https://www.cancer.gov/publications/dictionaries/cancer-terms/def/revuforj
- “FDA Approves Revuforj for Relapsed/Refractory Acute Leukemia Subset,” CURE; https://www.curetoday.com/view/fda-approves-revuforj-for-relapsed-refractory-acute-leukemia-subset
- “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,” news release; https://ir.syndax.com/news-releases/news-release-details/syndaxs-revuforjr-revumenib-included-nccn-clinical-practice
