FDA Grants Priority Review to Ziftomenib in NPM1-Mutant R/R AML

FDA

The FDA has granted priority review to the new drug application (NDA) seeking the full approval of ziftomenib (KO-539) for the treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) harboring an NPM1 mutation.1

The FDA has assigned a target action date of November 30, 2025, under the Prescription Drug User Fee Act.

The NDA is supported by data from the phase 1/2 KOMET-001 trial (NCT04067336), which met its primary end point of complete remission (CR) plus CR with partial hematologic recovery (CRi) rate. Regarding safety, the menin inhibitor was well tolerated, and myelosuppression was limited. Ziftomenib-related adverse effects led to treatment discontinuation in 3% of patients.

Full data from KOMET-001 will be presented on June 2, 2025, at the 2025 ASCO Annual Meeting.

“The FDA’s acceptance of our NDA marks a significant milestone for Kura [Oncology], Kyowa Kirin and, more importantly, for patients living with this genetic subset of AML, who face an aggressive form of the disease with few treatment options,” Troy Wilson, PhD, JD, president and chief executive officer of Kura Oncology, stated in a news release. “This achievement reflects the strength of the clinical data for ziftomenib as well as the incredible commitment of our teams. Along with our partners at Kyowa Kirin, we look forward to continuing to work closely with the FDA throughout the review process and to prepare for the anticipated launch of this treatment, which holds potential to meaningfully impact the lives of patients and their families.”

KOMET-001 Background

The first-in-human, open-label, dose-escalation and -validation/expansion trial enrolled patients at least 18 years of age with relapsed/refractory AML, defined as the re-emergence of a bone marrow blast level of at least 5%.2 Patients need to have disease that progressed on or was ineligible for standard-of-care therapies, including hematopoietic stem cell transplant (HSCT).

In phase 1b, patients needed to have AML harboring KMT2A rearrangements or NPM1 mutations; phase 2 was limited to patients with NPM1 mutations. Key inclusion criteria for all patients included an ECOG performance status of 0 to 2; a life expectancy of at least 2 months; and adequate liver and kidney function.

Patients were excluded if they had acute promyelocytic leukemia; had chronic myelogenous leukemia in blast crisis; had received a donor lymphocyte infusion less than 30 days prior to enrollment; had clinically active central nervous system leukemia; or had undergone HSCT and had not achieved adequate hematologic recovery.

Phase 1a served as a dose-escalation portion, and phase 1b was the trial’s dose-validation/expansion portion. In phase 2, patients with NMP1-mutant relapsed/refractory AML received ziftomenib at the recommended phase 2 dose (RP2D) established in phase 1.

The trial’s primary end points included determining the maximum tolerated dose/RP2D (phase 1a), safety (phase 1b), determining the minimal biologically effective dose (phase 1b), and CR/CRi rate (phase 2).

“Adult [patients with] relapsed/refractory, NPM1-mutant AML face a significantly poor prognosis, highlighting the urgent need for innovative treatment options that can improve their outcomes,” Takeyoshi Yamashita, PhD, executive vice president and chief medical officer of Kyowa Kirin, added in the news release.1 “The acceptance of this NDA is a crucial step in our ongoing efforts to explore and evaluate various therapeutic strategies for AML through our comprehensive clinical trials. Our dedicated teams at Kyowa Kirin and Kura are fully committed to working tirelessly to ensure that, once approved, ziftomenib is made available to [patients with] AML as quickly as possible. We recognize the importance of this endeavor and are excited about the possibility of making a meaningful impact on the lives of those affected by this challenging disease.”

References

1. Kura Oncology and Kyowa Kirin announce FDA acceptance and priority review of new drug application for ziftomenib in adults with relapsed or refractory NPM1-mutant AML. News release. Kura Oncology. June 1, 2025. Accessed June 2, 2025. https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-fda-acceptance-and
2. First in human study of ziftomenib in relapsed or refractory acute myeloid leukemia. ClinicalTrials.gov. Updated April 18, 2025. Accessed June 2, 2025. https://clinicaltrials.gov/study/NCT04067336