Syndax menin inhibitor gets its big day
Syndax has long led the menin inhibitor race, and yesterday it took a step closer to FDA approval, with its contender revumenib getting a 26 September PDUFA date. The indication sought is adult and paediatric relapsed/refractory KMT2Ar acute leukaemia; the fact the FDA accepted a filing including children, and ALL as well as AML, is good news for Syndax, as only around 25% of patients enrolled in the pivotal Augment-101 trial were under 18, and only 15% had ALL. The company looks set to have KMT2Ar disease to itself for some time: its main menin rival, Kura, abandoned monotherapy plans with its project ziftomenib in this genetic subtype. Here Kura is now focused on combinations, where it recently reported early data. Meanwhile, Johnson & Johnson’s JNJ-75276617 has produced decent results in KMT2Ar patients, but is well behind. In NPM1-mutant AML the race is closer, with both Syndax and Kura set to have enrolled their pivotal trials by mid-year. NPM1 mutations account for around 30% of AML cases, and KMT2Ar around 10%. The only thing that might trip revumenib up is side effects: menin inhibitors have been linked with QTc prolongation, differentiation syndrome and neutropenia.
Menin inhibitors race for approval
| Project | Company | Setting | Regimen | Status |
|---|---|---|---|---|
| Revumenib | Syndax | r/r KMT2Ar acute leukaemia | Monotherapy | PDUFA date 26 Sep 2024 (priority review); based on 23% CR/CRh rate in Augment-101 |
| r/r mNPM1 AML | Monotherapy | Enrolment into pivotal Augment-101 cohort to complete late Q1/early Q2 2024 | ||
| Ziftomenib | Kura | 1L & r/r KMT2Ar AML | Chemo or ven/aza combo* | Data from Komet-007 reported Jan 2024 |
| r/r mNPM1 AML | Monotherapy | Enrolment into pivotal Komet-001 cohort to complete mid-2024 |
Note: *Kura stopped monotherapy development in KMT2Ar AML in Feb 2023. Source: OncologyPipeline, clinicaltrials.gov & company releases.
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