Syndax Announces U.S. FDA Breakthrough Therapy Designation Granted for Patients with Relapsed or Refractory KMT2A- Rearranged (MLLr) Acute Leukemia

Syndax Pharmaceuticals, a clinical-stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for revumenib for the treatment of adult and pediatric patients with relapsed or refractory (R/R) acute leukemia harboring a KMT2A rearrangement (KMT2Ar). Revumenib is the Company’s highly selective, oral menin inhibitor.

“The Breakthrough Therapy Designation underscores revumenib’s potential as a first- and best-in-class therapy to meaningfully change the treatment paradigm for patients with R/R KMT2Ar acute leukemia, whether it presents clinically as acute myeloid leukemia (AML) or acute lymphocytic leukemia (ALL), in adults or children,” said Michael A. Metzger, Chief Executive Officer. “Revumenib has the potential, if approved, to be the first drug to address the significant unmet need in KMT2Ar leukemia believed to occur in up to 10% of all acute leukemias, including in approximately 80% of infant acute leukemias. Syndax is committed to bringing revumenib to these patients as quickly as possible and we look forward to working collaboratively with the FDA to expedite a potential approval of revumenib.”

The BTD is supported by Phase 1 data from the AUGMENT-101 trial. Ten of 37 patients (27%) with age and phenotype-agnostic KMT2Ar acute leukemia treated at doses meeting the protocol defined criteria for the recommended Phase 2 dose (RP2D) and evaluable for efficacy as of the March 2022 data cutoff achieved a complete remission as measured by a CR/CRh. Included in this analysis were patients treated in Arm A (226 and 276 mg q12 hours not receiving a strong CYP3A4 inhibitor) and Arm B (113 and 163 mg q12 hours receiving a strong CYP3A4 inhibitor).

As previously announced, additional data from the Phase 1 portion of the AUGMENT-101 trial will be presented during two oral sessions at the American Society of Hematology (ASH) Annual Meeting on December 10, 2022. The abstracts (Abstracts #63 and #376) describe data on the 60 patients with R/R mutant NPM1 (n=14) or KMT2A rearranged (MLLr; n=46) acute leukemia that were evaluable for efficacy as of the March 2022 data cutoff date. Additional analyses from the trial that will be presented at the ASH Annual Meeting indicate a 27% CR/CRh rate at doses meeting the protocol defined criteria for the RP2D in all efficacy evaluable patients (13/48) and in patients with an NPM1 mutation (3/11). There were no discontinuations due to treatment-related adverse events.

The FDA grants BTD to expedite the development and regulatory review of drugs that are intended for serious or life-threatening conditions. The designation is based on preliminary clinical evidence indicating that a drug may demonstrate substantial improvement on at least one clinically significant endpoint over available therapy. BTD affords all of the benefits of the fast track program, eligibility for rolling review and potentially priority review, and additional engagement to facilitate an expedited development plan and regulatory review.