FDA Extends PDUFA Date for Revumenib NDA for KMT2A-Rearranged Acute Leukemia

• The Prescription Drug User Fee Act (PDUFA) target action date for the new drug application (NDA) for revumenib (SNDX-5613) has been extended by the FDA.
• Revumenib is being developed to treat adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute leukemia.
• The updated target action date is December 26, 2024.

The FDA has deferred the PDUFA target action date for the NDA for revumenib, which seeks approval for treating adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute leukemia.1 The updated target action date is set for December 26, 2024.¹

On March 26, 2024, the FDA granted priority review to the NDA and set an original PDUFA target action date of September 26, 2024. However, on July 26, 2024, FDA notified Syndax, the agent’s manufacturer, that they needed additional time to conduct a full review of supplemental information provided to the FDA per their request.

This additional information was classified as a major amendment to the NDA, which resulted in a routine 3-month extension of the original target action date. The FDA has not requested any additional trials or manufacturing details from Syndax.

“Revumenib, upon approval, will be the first drug indicated to treat patients with KMT2A-rearranged acute leukemia, a population with significant unmet need,” said Michael A. Metzger, chief executive officer of Syndax, in a press release. “We are confident that the data from the AUGMENT-101 trial [NCT04065399], as well as the additional information provided to the FDA, support approval and continue to demonstrate the meaningful benefit revumenib brings to patients with this devastating disease. We look forward to continuing our engagement with the FDA as they complete their review of the NDA by December 26, 2024.”

About the AUGMENT-101 Trial

Data from the phase 1/2 AUGMENT-101 trial support the NDA. In the study, the first-in-class Menin inhibitor revumenib generated complete remissions (CRs) with a CR with partial hematologic recovery (CRh) rate of 23% (95% CI, 12.7%-35.8%; P =.0036) in adult and pediatric patients with relapsed/refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) harboring KMT2A rearrangements.² This was at a data cutoff of July 24, 2023, and observed in the 57 adult and pediatric patients with KMT2A-rearranged AML or ALL who were treated with revumenib monotherapy. The median time to CR/CRh was 1.9 months (95% CI, 0.9-4.5).

In the overall cohort, the overall response rate was 63% (95% CI, 49.3%-75.6%). Fourteen of 36 responders (39%) underwent subsequent hematopoietic stem cell transplant (HSCT), including 8 who did not reach a CR/CRh before transplant. Post transplant, half of the patients who underwent HSCT (n = 7) received revumenib maintenance, and 3 additional patients were in follow-up. These 3 patients were eligible to restart revumenib in the maintenance setting.

The median overall survival at the data cutoff was 8.0 months (95% CI, 4.1-10.9), the median duration of CR/CRh in the overall population and subset of patients with AML was 6.4 months (95% CI, 3.4-not reached), and 6 out of 13 patients (46%) continued to have a response. For minimal residual disease (MRD), MRD status was evaluated in 10 patients who had a CR/CRh, 70% of whom were MRD-negative. A total of 68% of the evaluable patients with a composite CR (n = 22) were MRD-negative.

For safety, any-grade treatment-related adverse events seen in over 20% of patients were nausea (28%), differentiation syndrome (27%), and QTc prolongation (23%). Grade 3 differentiation syndrome was observed in 15% of patients, and 1 patient had grade 4 differentiation syndrome. No patients had grade 5 differentiation syndrome. While grade 3 QTc prolongation was seen in 14% of patients, there were no grade 4 or 5 events observed. Additionally, no patients stopped treatment due to differentiation syndrome, QTc prolongation, or cytopenias.

REFERENCES:

1. Syndax announces PDUFA action date extension for revumenib NDA for relapsed or refractory KMT2Ar acute leukemia. News release. Syndax. July 29, 2024. Accessed July 29, 2024. https://tinyurl.com/2sbsymwb

2. Syndax presents positive data from pivotal AUGMENT-101 trial of revumenib in relapsed/refractory KMT2Ar acute leukemia at late-breaking oral presentation during 65th ASH Annual Meeting. News release. Syndax. December 12, 2023. Accessed July 29, 2024. ​​https://tinyurl.com/2p3yzrez