While awaiting an FDA decision for its small molecule revumenib in one form of acute leukemia, Syndax Pharmaceuticals is trying to build a case for its candidate in another. Though the drug met its primary endpoint in the phase 2 portion of a phase 1/2 trial, the results failed to impress investors, sending Syndax’s stock down 22%.
In the phase 2 portion of the phase 1/2 AUGMENT-101 trial, 12 of 64 patients with relapsed or refractory mutant NPM1 acute myeloid leukemia (AML) went into complete remission when given Syndax's revumenib, an oral small-molecule menin inhibitor. Three patients also had a complete remission but without higher white blood cell counts, known as a complete remission with partial hematological recovery, according to a Nov. 12 release.
The complete remission (CR) or CR with partial hematological recovery (CRh) rate remained the same as rates reported in the trial's phase 1 portion in October 2023. The treatment’s overall response rate was 47% in the phase 2 portion, down from 63% in the phase 1 part. The trial met its primary endpoint, which measured CR plus CRh rate.
As far as safety goes, four of 84 patients experienced treatment-related adverse events (TRAEs) that prompted them to stop treatment, according to Syndax. The biotech did not cite what specific TRAEs occurred for the participants that discontinued treatment.
Two patients experienced grade 4 QTc prolongation, meaning a dangerously slower heart rate, while two had grade 4 differentiation syndrome (DS), a condition that can be life-threatening.
Overall, more than 10% of patients experienced TRAEs of grade 3 level or higher, including QTc prolongation (21%); anemia (14%); febrile neutropenia (13%); differentiation syndrome (13%); and decreased platelet count (11%). No patient experienced a grade 5 event in DS or QTc prolongation, according to Syndax.
The median response duration was 4.7 months for the patients who had CR or CRh, Syndax said. Three patients were still responding to treatment at the time of data cutoff.
The top-line data failed to impress investors, with Syndax’s stock tumbling about 22% from $21.70 per share at yesterday’s market close to $16.80 today at 1 p.m. ET.
Massachusetts-based Syndax is currently awaiting a Dec. 26 approval decision by the FDA for revumenib in relapsed or refractory KMT2Ar acute leukemia. If approved, revumenib would become the first treatment for this type of acute leukemia. If this initial approval arrives on time, Syndax plans to file revumenib in previously treated mutant NPM1 AML in the first half of 2025.
"With the anticipated FDA approval of revumenib for the treatment of R/R KMT2A-rearranged acute leukemias this quarter, and this second positive pivotal data readout, we are well-positioned to meaningfully impact the estimated 40% of AML patients with these two genetic alterations,” Syndax CEO Michael Metzger said in the release.
Syndax recently geared up for commercialization by inking a $350 million deal with Royalty Pharma. That cash influx will be used to bring revumenib and approved graft-versus-host disease drug Niktimvo (axatilimab) to market.