FDA Approves Syndax's Revuforj® for Acute Leukemia with KMT2A Translocation

Syndax Pharmaceuticals has announced the U.S. Food and Drug Administration (FDA) approval of Revuforj® (revumenib), marking it as the first menin inhibitor for treating relapsed or refractory (R/R) acute leukemia with a lysine methyltransferase 2A gene (KMT2A) translocation. This approval encompasses both adult and pediatric patients aged one year and older, making it a significant milestone in the treatment landscape for this aggressive leukemia type. This approval process was expedited under the FDA's Real Time Oncology Review (RTOR) program, reflecting the urgency and importance of bringing this treatment to patients quickly.

Revuforj's approval is supported by positive results from the AUGMENT-101 clinical trial. This trial evaluated the efficacy and safety of Revuforj in patients with R/R acute leukemia featuring a KMT2A translocation. Among the 104 patients assessed, the treatment demonstrated a complete remission (CR) and CR with partial hematological recovery (CRh) rate of 21%. The median duration of this remission was 6.4 months, and 23% of the patients subsequently underwent hematopoietic stem cell transplantation (HSCT), highlighting the potential of Revuforj to serve as a bridge to further curative treatments.

The safety profile of Revuforj was analyzed in a larger cohort of 135 patients, where common adverse reactions included hemorrhage, nausea, increased phosphate levels, musculoskeletal pain, infections, liver enzyme increases, and differentiation syndrome, among others. Despite these adverse effects, the rate of discontinuation due to adverse reactions was relatively low, at 12%.

The approval of Revuforj signifies a crucial advancement for patients with KMT2A-rearranged acute leukemia, a condition characterized by high relapse rates and poor prognosis. Typically, over 95% of patients with this form of acute leukemia present with a KMT2A translocation, significantly complicating their treatment and survival outcomes. Conventional treatments often result in less than one year of overall survival, with a dismal complete remission rate in third-line or beyond treatments. The introduction of a menin inhibitor like Revuforj offers a new therapeutic mechanism, potentially altering the course of the disease by targeting the menin-KMT2A interaction critical for the leukemia's progression.

Syndax Pharmaceuticals is preparing for the immediate launch of Revuforj, with different dosage formats to accommodate varying patient needs. The 110 mg and 160 mg tablets will be available through specialty distributors in November, with a 25 mg tablet expected in early 2025. Meanwhile, an oral solution will be accessible under an expanded access program for younger children who weigh less than 40 kg.

In addition to making Revuforj available, Syndax is committed to patient support through their SyndAccess™ program, which provides personalized assistance and resources, including financial support for eligible patients. This comprehensive approach aims to reduce barriers to access and ensure that patients who need Revuforj can obtain it.

Revuforj is not only a breakthrough for KMT2A-rearranged acute leukemia but also shows promise for other related blood cancers. It is currently being investigated for its efficacy in acute myeloid leukemia (AML) with nucleophosmin 1 mutations (mNPM1). Ongoing trials are exploring the benefits of combining Revuforj with standard-of-care agents in various settings, including newly diagnosed patients.

Syndax Pharmaceuticals continues to innovate in cancer therapy, with Revuforj marking a significant step forward. Their pipeline also includes other promising treatments, such as Niktimvo™ (axatilimab-csfr), further showcasing their commitment to transforming cancer care and improving patient outcomes.