FDA Approval Is Sought for Ziftomenib in NMP1-Mutant R/R AML

FDA

A new drug application (NDA) seeking the approval of ziftomenib for the treatment of adult patients with relapsed/refractory acute myeloid leukemia (AML) displaying NMP1 mutations has been submitted to the FDA.1

Kura Oncology, the drug’s developer, anticipates a decision on potential acceptance of the NDA to be shared by the FDA in the second quarter of 2025, and has also requested priority review of the application. If granted, this would lead to a potential Prescription Drug User Fee Act target action date 6 months after NDA acceptance.

“This NDA submission brings us one step closer to our goal of advancing ziftomenib to market as a new therapeutic option for adult patients with relapsed/refractory NPM1-mutant AML, a devastating disease for which there are currently no FDA-approved targeted therapy options,” Troy Wilson, PhD, JD, president and chief executive officer of Kura Oncology, stated in a news release. “We look forward to working closely with the FDA throughout the review process and are optimistic about the potential of ziftomenib to impact patients with NPM1-mutant AML. We extend our gratitude to the team at Kura, our dedicated investigators, study site teams, and most importantly, to the patients who participated in our clinical trials, and their families and caregivers, who all helped make this possible. We appreciate the support and cooperation we enjoy with our partner Kyowa Kirin, and we look forward with confidence to the continued progress of this program and our collaboration.”

In February 2025, Kura Oncology shared that ziftomenib had met the primary end point of complete remission (CR) plus CR with partial hematological recovery (CRh) of the multicenter, open-label, multicohort, phase 2 KOMET-001 trial (NCT04067336), which is evaluating the investigational once-daily oral menin inhibitor in patients with relapsed or refractory NPM1-mutant AML.2,3 The agent demonstrated an encouraging risk-benefit profile with safety and tolerability consistent with earlier reports.2

Previously published data from the phase 1a/1b portion of KOMET-001 showed that in phase 1b, no responses were observed among patients treated at the 200-mg dose level.3 At the recommended phase 2 dose of 600 mg, 25% of patients with either a KMT2A rearrangement or NPM1 mutation (n = 36) achieved a CR/CRh. Among those with NPM1 mutations (n = 20), 35% of patients treated at this dose achieved CR.

Across the 83 patients evaluated, the most common grade 3 or higher treatment-emergent adverse effects (AEs) included anemia (24%), febrile neutropenia (22%), pneumonia (19%), differentiation syndrome (15%), thrombocytopenia (13%), and sepsis (12%). Serious AEs occurred in 68 patients, including 2 treatment-related deaths—1 due to differentiation syndrome and 1 due to cardiac arrest. The incidence and severity of differentiation syndrome led to a decision to halt further enrollment of patients with KMT2A rearrangements.

Results from this study supported the agent’s prior receipt of breakthrough therapy designation for relapsed/refractory NPM1-mutant AML in April 2024, making ziftomenib the first investigational agent to be granted such designation in this patient population.4 Ziftomenib was also previously granted FDA fast track and orphan drug designations in AML.1

Upcoming evaluations of ziftomenib include the phase 3 KOMET-017 clinical program, which will assess the use of this agent in frontline combination regimens.2 KOMET-017-IC will assess ziftomenib vs placebo alongside 7+3 induction chemotherapy in patients with newly diagnosed AML harboring NPM1 mutations or KMT2A rearrangements; KOMET-017-NIC will evaluate ziftomenib or placebo plus venetoclax (Venclexta) and azacitidine (Vidaza) in patients with newly diagnosed NPM1-mutant AML who are ineligible for intensive chemotherapy. Enrollment for both trials is expected to begin in the second half of 2025.

References

1. Kura Oncology and Kyowa Kirin Announce Submission of New Drug Application for Ziftomenib to FDA. News Release. Kura Oncology. April 8, 2025. Accessed April 8, 2025. https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-and-kyowa-kirin-announce-submission-new-drug
2. Kura Oncology and Kyowa Kirin announce positive ziftomenib monotherapy registrational trial and positive FDA feedback for upcoming frontline combination trial designs. News Release. Kura Oncology. February 5, 2025. Accessed April 8, 2025. https://www.globenewswire.com/news-release/2025/04/08/3057507/35186/en/Kura-Oncology-and-Kyowa-Kirin-Announce-Submission-of-New-Drug-Application-for-Ziftomenib-to-FDA.html
3. Wang ES, Issa GC, Erba HP, et al. Ziftomenib in relapsed or refractory acute myeloid leukaemia (KOMET-001): a multicentre, open-label, multi-cohort, phase 1 trial. Lancet Oncol. 2024;25(10):1310-1324. doi:10.1016/S1470-2045(24)00386-3
4. Kura Oncology receives breakthrough therapy designation for ziftomenib in NPM1-mutant AML. News release. Kura Oncology. April 22, 2024. Accessed April 8, 2025. https://ir.kuraoncology.com/news-releases/news-release-details/kura-oncology-receives-breakthrough-therapy-designation