FDA Approves Kura and Kyowa Kirin's Komzifti for Subset of AML Patients

The U.S. Food and Drug Administration (FDA) has granted approval to Komzifti (ziftomenib), a new oral medication developed by Kura Oncology and Kyowa Kirin for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) harboring a susceptible nucleophosmin 1 (NPM1) mutation. This approval marks a significant milestone in the treatment of AML, a disease where specific options for patients with NPM1 mutations have been historically limited.

A New Option for NPM1-Mutated AML

Komzifti, a menin inhibitor, is indicated for patients who are not suitable candidates for alternative treatments. The drug's approval is based on the results of the pivotal KOMET-001 trial, which demonstrated promising efficacy in this patient population. According to the study data, 21.4% of patients achieved complete remission (CR) or CR with partial hematologic recovery (CRh), with a median duration of remission of 5 months among responders.

NPM1 mutations are among the most common founder mutations in AML, affecting approximately one-third of patients. The approval of Komzifti addresses a significant unmet need, as about 20% of patients with NPM1-mutated AML do not respond to frontline therapy, and of those who do respond, roughly 70% relapse within three years.

Competitive Landscape and Safety Considerations

Komzifti enters a market recently opened by Syndax Pharmaceuticals' Revuforj, which received FDA approval in late October as the first menin inhibitor for this indication. Both drugs will likely compete directly in this subset of AML patients.

While Komzifti demonstrates efficacy, it does carry a boxed warning for differentiation syndrome, a potentially severe reaction to certain leukemia treatments. The drug's label also includes precautions regarding QTc interval prolongation and embryo-fetal toxicity. These safety considerations are similar to those of Revuforj, although analysts at Mizuho Securities have suggested that Komzifti's overall safety profile "looks a bit better."

Strategic Partnership and Commercialization Plans

The approval of Komzifti represents a successful outcome for the partnership between Kura Oncology and Kyowa Kirin. The collaboration, formed in November 2024, involved a $330 million upfront payment from Kyowa Kirin to Kura, with the potential for up to $1.1 billion in additional milestone payments.

Under the terms of their agreement, Kura is responsible for development, regulatory affairs, and commercial strategy in the United States, as well as manufacturing. Kyowa Kirin manages R&D and marketing activities outside the U.S. Following the FDA approval, the partners will jointly execute certain commercialization activities in the U.S. market according to a co-created territory commercialization plan.

Troy Wilson, Ph.D., CEO of Kura, emphasized the drug's potential, stating, "Komzifti combines compelling efficacy, a favorable safety profile, compatibility with concomitant medications, and convenient once-daily oral administration in a population with few effective treatment options. These features highlight Komzifti's potential to serve as the menin inhibitor of choice in its approved indication."