FDA

First menin inhibitor approved for acute leukemia

November 19, 2024

Brand name: Revuforj

Generic name: revumenib

Manufacturer: Syndax Pharmaceuticals

Approval date: November 15, 2024

FDA approved Revuforj (revumenib), a menin inhibitor, for relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and pediatric patients ≥1 year of age.

Efficacy

Efficacy was evaluated in a single-arm cohort of the open-label, multicenter AUGMENT-101 trial (NCT04065399) involving 104 adult and pediatric patients (at least 30 days old) with R/R acute leukemia with a KMT2A translocation. Patients with an 11q23 partial tandem duplication were excluded. Revumenib was administered until disease progression, unacceptable toxicity, failure to achieve morphological leukemia-free state by 4 cycles of treatment, or hematopoietic stem cell transplantation (HSCT).

Main efficacy outcome measures were complete remission (CR) plus CR with partial hematologic recovery (CRh), duration of CR+CRh, and conversion from transfusion dependence to independence. CR+CRh rate was 21.2% (95% CI: 13.8, 30.3), and the median CR+CRh duration was 6.4 months (95% CI: 2.7, not estimable). Of the 22 patients achieving CR or CRh, median time to CR or CRh was 1.9 months (range: 0.9, 5.6 months). Among the 83 patients dependent on RBC and/or platelet transfusions at baseline, 12 (14%) became independent of RBC and platelet transfusions during any 56-day post-baseline period. Of the 21 patients independent of both RBC and platelet transfusions at baseline, 10 (48%) remained transfusion independent during any 56-day post-baseline period.

Safety

The most common adverse reactions (≥20%) were hemorrhage, nausea, increased phosphate, musculoskeletal pain, infection, increased AST, febrile neutropenia, increased ALT, increased intact PTH, bacterial infection, diarrhea, differentiation syndrome, QT prolongation, decreased phosphate, increased triglycerides, decreased potassium, decreased appetite, constipation, edema, viral infection, fatigue, and increased alkaline phosphatase.

Recommended dose

The recommended dose of revumenib varies by patient weight and concomitant use of strong CYP3A4 inhibitors. Due to an anticipated delay in commercial availability of the lowest dose strength of revumenib, which may be used to treat patients who weigh <40 kg, revumenib will be available through an expanded access program to allow for dosing of patients who weigh <40 kg.

Source:

FDA. (2024, November 15). FDA approves revumenib for relapsed or refractory acute leukemia with a KMT2A translocation. [Press release]. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-revumenib-relapsed-or-refractory-acute-leukemia-kmt2a-translocation

Syndax Pharmaceuticals. (2024, November 15). Syndax Announces FDA Approval of Revuforj (revumenib), the First and Only Menin Inhibitor to Treat Adult and Pediatric Patients with Relapsed or Refractory Acute Leukemia with a KMT2A Translocation. [Press release]. https://ir.syndax.com/news-releases/news-release-details/syndax-announces-fda-approval-revuforjr-revumenib-first-and-only