The FDA has prolonged the Prescription Drug Person Payment Act (PDUFA) goal motion date for the brand new drug software (NDA) looking for the approval of revumenib (SNDX-5613) for the therapy of grownup and pediatric sufferers with relapsed/refractory KMT2A-rearranged acute leukemia.1
The up to date goal motion date is December 26, 2024. When the FDA granted precedence evaluation to the NDA on March 26, 2024, the unique PDUFA goal motion date was September 26, 2024.2
On July 26, 2024, the FDA notified Syndax Prescription drugs that extra time was required to conduct a full evaluation of the supplemental details about revumenib that Syndax supplied to the FDA as requested.1 The submission of this extra info was deemed a Main Modification to the NDA and resulted in a normal 3-month extension to the unique goal motion date. The FDA has not requested extra trials or manufacturing info from Syndax.
“Revumenib, upon approval, would be the first drug indicated to deal with sufferers with KMT2A-rearranged acute leukemia, a inhabitants with important unmet want,” Michael A. Metzger, chief government officer of Syndax, said in a information launch. “We’re assured that the information from the [phase 1/2] AUGMENT-101 trial [NCT04065399], in addition to the extra info supplied to the FDA, assist approval and proceed to display the significant profit revumenib brings to sufferers with this devastating illness. We sit up for persevering with our engagement with the FDA as they full their evaluation of the NDA by December 26, 2024.”
The NDA is supported by findings from AUGMENT-101, through which, at a knowledge cutoff of July 24, 2023, grownup and pediatric sufferers with KMT2A-rearranged acute myeloid leukemia (AML) or acute lymphocytic leukemia who have been handled with revumenib monotherapy (n = 57) achieved a whole response (CR)/CR with a partial hematologic restoration (CRh) fee 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 fee was 23% (n = 10/44; 95% CI, 11.5%-37.8%) amongst evaluable grownup sufferers and 23% (n = 3/13; 95% CI, 5.0%-53.8%) amongst evaluable pediatric sufferers.
The whole inhabitants achieved an total response fee 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 didn’t obtain a CR/CRh previous to transplant. Seven of the sufferers who underwent HSCT obtained post-transplant revumenib upkeep, and on the knowledge cutoff, 3 extra sufferers have been in follow-up and have been eligible to restart revumenib as post-transplant upkeep. The median total survival on the knowledge cutoff was 8.0 months (95% CI, 4.1-10.9).
The median period of CR/CRh in each the general inhabitants and the AML subset was 6.4 months (95% CI, 3.4–not reached), and 46% of sufferers (n = 6/13) remained in response. Minimal residual illness (MRD) standing was evaluated in 10 sufferers who achieved a CR/CRh, 70% of whom have been MRD unfavourable. Amongst evaluable sufferers who achieved a composite CR (n = 22), 68% have been MRD unfavourable.
Any-grade TRAEs noticed in additional than 20% of sufferers included nausea (28%), differentiation syndrome (27%), and QTc prolongation (23%). Fifteen p.c of sufferers had grade 3 differentiation syndrome, 1 affected person had grade 4 differentiation syndrome, and no sufferers had grade 5 differentiation syndrome. Grade 3 QTc prolongation was seen in 14% of sufferers; nonetheless, no grade 4 or 5 occasions have been noticed. No sufferers discontinued therapy attributable to differentiation syndrome, QTc prolongation, or cytopenias.
References
- Syndax proclaims PDUFA motion date extension for revumenib NDA for relapsed or refractory KMT2Ar acute leukemia. Information launch. 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
- Syndax proclaims FDA precedence evaluation of NDA for revumenib for the therapy of relapsed/refractory KMT2Ar acute leukemia. Information launch. 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
- Syndax presents constructive knowledge from pivotal AUGMENT-101 trial of revumenib in relapsed/refractory KMT2Ar acute leukemia at late-breaking oral presentation throughout sixty fifth ASH Annual Assembly. Information launch. 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
