The U.S. Food and Drug Administration (FDA) has granted approval to Syndax Pharmaceuticals' Revuforj (revumenib) for the treatment of relapsed or refractory (R/R) acute leukemia in patients with a lysine methyltransferase 2A (KMT2A) translocation. This approval marks a significant advancement in the treatment of this aggressive form of leukemia, providing a new therapeutic option for patients who have limited alternatives. Revuforj is the first and only menin inhibitor approved for patients aged one year and older with this specific genetic alteration.
Clinical Efficacy and Trial Data
The approval was based on data from the Phase I/II AUGMENT-101 trial, which included 104 patients with R/R acute leukemia harboring KMT2A translocation. The study demonstrated clinically meaningful efficacy, with 21% of patients achieving complete remission with partial hematological recovery. The median duration of these responses was 6.4 months, with a median time to response of 1.9 months. Notably, 23% of patients were able to proceed to hematopoietic stem cell transplantation following treatment with revumenib, suggesting its potential to facilitate access to curative therapy.
The results align with the Phase II interim analysis from the same trial, reinforcing the potential of Revuforj in treating this aggressive leukemia form.
The safety profile was assessed in 135 patients, forming part of the FDA's analysis for approval.
Mechanism of Action and Target Population
Revuforj functions as a menin inhibitor, targeting a key protein involved in the pathogenesis of KMT2A-rearranged leukemia. This specific targeting offers a more precise approach compared to traditional chemotherapy, potentially reducing off-target effects and improving patient outcomes. The approval addresses a critical unmet need in patients with R/R acute leukemia who have failed prior lines of therapy.
Regulatory Pathway and Availability
The FDA expedited the approval of Revuforj through the Real Time Oncology Review program, following the granting of breakthrough therapy, fast track designations, and priority review. Syndax Pharmaceuticals anticipates that Revuforj 110mg and 160mg tablets will be available in the US through specialty distributors and pharmacies starting in November 2024. Furthermore, 25mg tablets, designed for patients weighing under 40kg, are expected to be available by early 2025, with an interim oral solution provided through an expanded access program, ensuring accessibility for all eligible patients.
Company Leadership Perspective
Syndax Pharmaceuticals CEO Michael Metzger stated: "The approval of Revuforj is a remarkable achievement that reflects the dedication and tenacity of everyone involved, especially the patients and clinicians who participated in our trial and our talented Syndax team."
He added, "We are well-prepared to launch Revuforj this month and we are committed to rapidly advancing the development of Revuforj across the treatment continuum for KMT2A-rearranged acute leukaemia’s and mutant NPM1 AML."
