FDA Greenlights Revumenib for Patients with Relapsed or Refractory Acute Leukemia Featuring KMT2A Translocation

FDA Greenlights Revumenib for Patients with Relapsed or Refractory Acute Leukemia Featuring KMT2A Translocation

FDA Greenlights Revumenib for Patients with Relapsed or Refractory Acute Leukemia Featuring KMT2A Translocation

On November 15, 2024, the Food and Drug Administration granted approval for revumenib (Revuforj, Syndax Pharmaceuticals, Inc.), a menin inhibitor aimed at treating relapsed or refractory acute leukemia characterized by a lysine methyltransferase 2A gene (KMT2A) translocation in both adult and pediatric patients aged 1 year and older.

Comprehensive prescribing details for Revuforj will be available on Drugs@FDA.

Efficacy and Safety

The efficacy of revumenib was assessed through a single-arm cohort of an open-label, multicenter clinical trial (SNDX-5613-0700, NCT04065399; AUGMENT-101), which included 104 patients (at least 30 days old) suffering from relapsed or refractory acute leukemia featuring a KMT2A translocation. Those with an 11q23 partial tandem duplication were excluded from the trial. Treatment with revumenib continued until disease progression, intolerable toxicity, failure to achieve a morphological leukemia-free state after 4 treatment cycles, or the patient received hematopoietic stem cell transplantation (HSCT).

The primary efficacy metrics included complete remission (CR) alongside CR with partial hematologic recovery (CRh), the length of CR+CRh, and the shift from transfusion dependence to independence. The CR+CRh rate stood at 21.2% (95% CI: 13.8, 30.3), with the median duration of CR+CRh recorded at 6.4 months (95% CI: 2.7, not estimable). Among the 22 patients reaching CR or CRh, the median time to achieve this was 1.9 months (range: 0.9, 5.6 months). From the 83 patients reliant on red blood cell (RBC) and/or platelet transfusions at the start, 12 (14%) progressed to independence from transfusions during any given 56-day period following baseline. Conversely, 10 out of 21 patients (48%) who were initially independent of both RBC and platelet transfusions maintained this status during any post-baseline 56-day segment.

Noteworthy adverse reactions occurring in ≥20% of participants included hemorrhage, nausea, elevated phosphate levels, musculoskeletal pain, infections, increased liver enzymes, febrile neutropenia, differentiation syndrome, and various electrolyte imbalances among others.

The suggested dosage of revumenib is contingent on the patient’s weight and the concurrent use of strong CYP3A4 inhibitors. For specific dosage guidelines, refer to the prescribing information. Given a projected delay in the market availability of the lowest dose suitable for patients weighing less than 40 kg, revumenib will be provided via an expanded access program designed to facilitate treatment for those under this weight threshold (more details can be found at NCT05918913).

This assessment relied on the Real-Time Oncology Review (RTOR) pilot program, which expedited data submission leading up to the completion of the full clinical application, paired with the Assessment Aid, a voluntary submission provided to assist the FDA’s review process. The FDA endorsed this application 6 weeks before its scheduled target date.

Expedited Programs

This application attained priority review status. Revumenib also holds breakthrough and orphan drug designations. The FDA’s expedited programs are detailed in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals are urged to report all serious adverse events believed to be linked to any drug or medical device utilizing the FDA’s MedWatch Reporting System or by contacting 1-800-FDA-1088.

For help with single-patient INDs for investigational oncology products, healthcare providers can reach out to OCE’s Project Facilitate at 240-402-0004 or via email at OncProjectFacilitate@fda.hhs.gov.

Stay updated by following the Oncology Center of Excellence on X: @FDAOncology.