Syndax revumenib shows broad activity across leukaemia studies at EHA
Syndax Pharmaceuticals used the European Hematology Association Congress in Stockholm this week to present a broad clinical dataset for its approved menin inhibitor revumenib (Revuforj), with 12 accepted abstracts spanning relapsed/refractory and frontline acute leukaemia. The results, drawn from real-world studies, post-transplant analyses, and combination trials, collectively suggest durable remissions across three genetically defined patient populations: those with NPM1 mutations (NPM1m), KMT2A rearrangements (KMT2Ar), and NUP98 rearrangements (NUP98r).
Nick Botwood, chief medical officer at Syndax, said the breadth of data "bolsters our conviction that our ongoing pivotal frontline combination trials are positioned to deliver paradigm-changing results." The company softened that framing somewhat by noting that durability data from the newly diagnosed combination cohorts are still maturing, with median follow-up of less than five months in the most recently opened dose level.
Key efficacy readouts
The headline figures span five datasets. In a real-world interim analysis from the ROAR study, 82% of 11 heavily pretreated R/R patients achieved an overall response, with 64% reaching complete remission or complete remission with partial haematological recovery. A Phase 1 combination trial in newly diagnosed NPM1m or KMT2Ar AML reported a composite complete remission rate of 97% across 35 patients, with 86% measurable residual disease (MRD) negativity among those who achieved a composite complete remission.
Post-transplant data from a post-hoc analysis of the AUGMENT-101 trial showed a one-year overall survival rate of 95% among 19 adults and children who resumed revumenib following haematopoietic stem cell transplant, with median overall survival not yet reached. In the all-oral SAVE combination trial, which paired revumenib with venetoclax and decitabine/cedazuridine in R/R patients, the overall response rate was 88% with a 45% transplant rate and a median follow-up of 22 months, making it the most mature dataset presented. A separate analysis in the difficult-to-treat NUP98r subtype recorded a 28% overall response rate with a median duration of response of 6.7 months, modest figures that nonetheless represent a signal in a population with few alternatives.
Safety data across studies were broadly consistent with revumenib's established label, which carries boxed warnings for differentiation syndrome and QTc prolongation. The EHA datasets reported no Grade 3 or above differentiation syndrome or QTc events in the combination or real-world cohorts, a profile the company characterised as reassuring given the combination partners involved.
Market context and competitive read-across
Revumenib received FDA approval in late 2023 for R/R AML with susceptible NPM1 mutations and for R/R acute leukaemia with KMT2A translocations, making it the first approved menin inhibitor. The mechanistic class has attracted significant investment, with a number of programmes from other companies in earlier clinical development. The pivotal question for Syndax's commercial trajectory is whether combination data in the frontline setting, due from its ongoing pivotal trials, will be strong enough to support label expansion and displace or supplement established induction regimens. The SAVE trial's 22-month follow-up and the high MRD-negativity rates will likely draw close scrutiny from haematologists and payers seeking evidence of long-term disease control rather than remission rates alone.
Frontline AML remains a contested and commercially significant segment. Established combinations such as venetoclax plus azacitidine have set a high bar for overall survival benefit. Syndax's strategy of layering revumenib onto existing backbones rather than pursuing monotherapy in the frontline reflects the prevailing logic in the field, though longer follow-up will be needed before any claim of superiority or clear differentiation can be substantiated.