Syndax Pharmaceuticals announced that its Phase II AUGMENT-101 trial of revumenib achieved its primary endpoint in adults with relapsed or refractory mutant NPM1 acute myeloid leukemia (AML). The trial's success, however, was met with investor skepticism, as Syndax's stock price fell by 25.6% following the announcement.
The AUGMENT-101 trial (NCT04065399) evaluated the safety and efficacy of revumenib in patients with relapsed or refractory mutant NPM1 AML, a genetically defined and challenging-to-treat subtype of AML. The study enrolled adults with a median age of 65 years who had undergone extensive prior treatments; 75% had previously received venetoclax, and 36% had tried three or more lines of therapy.
Efficacy and Response Rates
Among the 64 efficacy-evaluable patients from the Phase II cohorts, 23% achieved complete remission (CR) or CR with partial haematological recovery (CRh). This included 12 patients with full remission and three with partial recovery. The median duration of response was 4.7 months, and 64% of tested patients were MRD-negative, indicating no detectable cancer cells after treatment. The trial also reported an overall response rate (ORR) of 47%, with five responders proceeding to stem cell transplants.
Safety Profile
Safety was assessed in 84 adult and paediatric patients. Four patients discontinued treatment due to treatment-related adverse events (TRAEs). More than 10% of patients reported Grade 3 or higher TRAEs, and Grade 4 events included QTc prolongation and differentiation syndrome (DS), a potentially life-threatening condition.
The safety profile observed with revumenib in this population was consistent with previously reported Phase I data, which showed a higher ORR of 63%.
Competitive Landscape
The treatment landscape for relapsed or refractory mNPM1 AML remains challenging, with chemotherapy and therapies like venetoclax more commonly used for other types of AML. Newer treatments, such as revumenib, are being explored in clinical trials to provide options for patients who do not respond to standard therapies. Revumenib functions by blocking the interaction between menin and mixed lineage leukaemia (MLL) fusion proteins, which are key drivers of leukaemia.
Syndax and Kura Oncology are both developing menin inhibitors that disrupt the same menin-MLL1 interaction. As of September 2024, Kura completed enrolment in its Phase II KOMET-001 trial of ziftomenib for R/R NPM1-mutant AML. Revumenib may have the first-mover advantage as it awaits approval in the KMT2A-rearranged subgroup of R/R AML and acute lymphocytic leukaemia, with a Prescription Drug User Fee Act (PDUFA) date of 26 December 2024.
According to GlobalData’s Pharma Intelligence Center, revumenib is projected to generate $634m by 2030, while ziftomenib could reach $583m in the same year.
