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

FDA

The FDA has extended the Prescription Drug User Fee Act (PDUFA) target action date for the new drug application (NDA) seeking the approval of revumenib (SNDX-5613) for the treatment of adult and pediatric patients with relapsed/refractory KMT2A-rearranged acute leukemia.¹

The updated target action date is December 26, 2024. When the FDA granted priority review to the NDA on March 26, 2024, the original PDUFA target action date was September 26, 2024.²

On July 26, 2024, the FDA notified Syndax Pharmaceuticals that more time was required to conduct a full review of the supplemental information about revumenib that Syndax provided to the FDA as requested.¹ The submission of this additional information was deemed a Major Amendment to the NDA and resulted in a standard 3-month extension to the original target action date. The FDA has not requested additional trials or manufacturing information 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,” Michael A. Metzger, chief executive officer of Syndax, stated in a news release. “We are confident that the data from the [phase 1/2] 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.”

The NDA is supported by findings from AUGMENT-101, in which, at a data cutoff of July 24, 2023, adult and pediatric patients with KMT2A-rearranged acute myeloid leukemia (AML) or acute lymphocytic leukemia who were treated with revumenib monotherapy (n = 57) achieved a complete response (CR)/CR with a partial hematologic recovery (CRh) rate of 23% (95% CI, 12.7%-35.8%; 1-sided P = .0036) with a median time to CR/CRh of 1.9 months (95% CI, 0.9-4.5).³ The CR/CRh rate was 23% (n = 10/44; 95% CI, 11.5%-37.8%) among evaluable adult patients and 23% (n = 3/13; 95% CI, 5.0%-53.8%) among evaluable pediatric patients.

The entire population achieved an overall response rate of 63% (95% CI, 49.3%-75.6%), and 39% of responders (n = 14/36) underwent subsequent hematopoietic stem cell transplant (HSCT), 8 of whom did not achieve a CR/CRh prior to transplant. Seven of the patients who underwent HSCT received post-transplant revumenib maintenance, and at the data cutoff, 3 additional patients were in follow-up and were eligible to restart revumenib as post-transplant maintenance. 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 both the overall population and the AML subset was 6.4 months (95% CI, 3.4–not reached), and 46% of patients (n = 6/13) remained in response. Minimal residual disease (MRD) status was evaluated in 10 patients who achieved a CR/CRh, 70% of whom were MRD negative. Among evaluable patients who achieved a composite CR (n = 22), 68% were MRD negative.

Any-grade TRAEs observed in more than 20% of patients included nausea (28%), differentiation syndrome (27%), and QTc prolongation (23%). Fifteen percent of patients had grade 3 differentiation syndrome, 1 patient had grade 4 differentiation syndrome, and no patients had grade 5 differentiation syndrome. Grade 3 QTc prolongation was seen in 14% of patients; however, no grade 4 or 5 events were observed. No patients discontinued 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://ir.syndax.com/news-releases/news-release-details/syndax-announces-pdufa-action-date-extension-revumenib-nda
2. Syndax announces FDA priority review of NDA for revumenib for the treatment of relapsed/refractory KMT2Ar acute leukemia. News release. Syndax. March 26, 2024. Accessed July 29, 2024. https://ir.syndax.com/news-releases/news-release-details/syndax-announces-fda-priority-review-nda-revumenib-treatment
3. 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://ir.syndax.com/news-releases/news-release-details/syndax-presents-positive-data-pivotal-augment-101-trial