Revumenib Earns FDA Priority Review in R/R KMT2Ar Acute Leukemia

• Priority review from the FDA has been granted to the new drug application (NDA) for revumenib in adult and pediatric relapsed or refractory (R/R) KMT2A-rearranged acute leukemia.
• Findings from the AUGMENT-101 trial (NCT04065399) evaluating revumenib in adult and pediatric patients with KMT2A-rearranged acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) support this decision.
• A Prescription Drug User Fee Act (PDUFA) target action date has been set for September 26, 2024.

The FDA granted priority review to the NDA for revumenib in adult and pediatric R/R KMT2A-rearranged acute leukemia.¹

Revumenib is a first-in-class Menin inhibitor. The NDA filing for the agent is currently being reviewed under the FDA's real-time oncology review program, which allows for a more efficient review and engagement between the sponsor and the FDA throughout the submission process.

A PDUFA date for the agent has been set for September 26, 2024.

"The receipt of priority review for the revumenib NDA filing is a significant milestone as we transition to a leading commercial-stage oncology company with the planned launches of 2 first- and best-in class drugs in 2024," said Michael A. Metzger, chief executive officer of Syndax Pharmaceuticals, in a press release. "With 2 regulatory filings now under FDA priority review, our team is focused on commercial preparations to enable Syndax's continued success as we enter this next stage of growth."

a close-up of red blood cells flowing through a vein, displaying the characteristic sickle shape Generative AI: © catalin - stock.adobe.com

Data From the AUGMENT-101 Trial

Findings from the AUGMENT-101 trial of revumenib in adult and pediatric patients with KMT2A-rearranged AML and ALL support this approval. At the protocol-defined interim analysis, the trial met its primary end point by showing a complete remission (CR) or a CR with partial hematologic recovery (CRh) rate of 23% (95% CI, 12.7%-35.8%; P =.0036).2 This was seen among the 57 patients who were in the pooled KMT2Ar acute leukemia population and were efficacy-evaluable.

In both the overall population and among patients with AML, a durable CR/CRh response was seen with a 6.4-month (95% CI, 3.4-not reached) median duration as of the data cutoff date of July 24, 2023. At this time, 46% of patients remained in response.

Ten of the 13 patients who achieved CR/CRh had minimal residual disease (MRD) status assessed, and 70% of patients were MRD-negative. In the overall cohort of 57 patients, 36 achieved an overall response, 39% (14/36) of whom underwent hematopoietic stem cell transplant. Additionally, 50% of these patients (7/14) restarted revumenib as post transplant maintenance at the time of the data cutoff.

Further findings from phase 2 AUGMENT-101 trial in this patient population were presented at the 2023 American Society of Hematology Annual Meeting. Data from the phase 1 portion of the AUGMENT-101 trial in acute leukemia were also published in Nature.¹

Previously, in December 2022, the FDA granted a breakthrough therapy designation to revumenib for the treatment of adult and pediatric patients with R/R acute leukemia who harbor a KMT2A rearrangement.

REFERENCES:

1. Syndax announces FDA priority review of NDA for revumenib for the treatment of relapsed/refractory KMT2Ar acute leukemia. News release. Syndax Pharmaceuticals. March 26, 2024. Accessed March 26, 2024. https://tinyurl.com/27x4vena

2. Aldoss I, Issa GC, Thirman M, et al. Revumenib monotherapy in patients with relapsed/refractory acute leukemia topline efficacy and safety results from the pivotal augment-101 phase 2 study. Blood. 2023;142(supple 2): LBA-5. doi:10.1182/blood-2023-192042