Novel Inhibitor approved as a Breakthrough Therapy for the Treatment of Acute Leukemia
The U.S. Food and Drug Administration has given the oral menin inhibitor Revumenib a breakthrough therapy designation (BTD).
Revumenib is used to treat patients with relapsed or refractory acute leukemia harboring a KMT2A arrangement (KMT2Ar).
The designation was supported by data from phase 1 of the AUGMENT-101 trial (NCT04065399), which demonstrated that revumenib produced a complete remission (CR) rate of 27% among 37 patients with relapsed or refractory KMT2A-rearranged acute leukaemia, defined as a CR or a CR with partial hematologic recovery (CRh).
Patients receiving revumenib doses of 226 mg and 276 mg every 12 hours who were not getting a strong CYP3A4 inhibitor (arm A) and patients receiving revumenib doses of 113 mg and 163 mg every 12 hours who were receiving a strong CYP3A4 inhibitor were included in the efficacy analysis (arm B).
The drug revumenib is being developed to treat acute leukaemias with KMT2A rearrangements, such as ALL, AML, and NPM1-mutant AML. It is a powerful, selective, small-molecule inhibitor of the menin-MLL binding relationship.
The objective of the open-label phase 1/2 AUGMENT-101 experiment is to assess the safety, tolerability, pharmacokinetics, and effectiveness of oral revumenib.
KMT2Ar acute leukaemia is commonly identified using currently available cytogenetic or molecular diagnostic methods. It can phenotypically present as AML, ALL, or mixed phenotype acute leukaemia (MPAL).
