The US Food and Drug Administration (FDA) has approved KOMZIFTI (ziftomenib), developed by Kura Oncology and Kyowa Kirin, for adults with relapsed or refractory (R/R) acute myeloid leukemia (AML) harboring an NPM1 mutation and with no satisfactory alternative treatment options.

KOMZIFTI is the first and only once-daily, oral menin inhibitor approved for this genetically defined subtype of AML, a disease with poor outcomes and limited therapeutic options.

Approval was granted ahead of the target action date and is supported by data from the KOMET-001 trial (NCT04067336). In the pivotal study, KOMZIFTI achieved a 21.4% rate of complete remission (CR) plus CR with partial hematologic recovery (CRh) among 112 adults with R/R NPM1-mutated AML. The median duration of CR+CRh was five months, and most responders achieved remission within six months of treatment.

Troy Wilson, president and chief executive officer at Kura Oncology, said: “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.”

NPM1 mutations occur in around 30% of AML cases and are associated with relapse and reduced survival. Around 20% of patients do not respond to initial therapy, and up to 70% relapse within three years.

Eunice Wang, chief of the leukemia service at Roswell Park Comprehensive Cancer Center, said: “KOMZIFTI addresses a critical need for adult patients with R/R NPM1-m AML, many of whom are older and unable to tolerate intensive chemotherapy or transplant. The clinical data demonstrate deep and durable responses with a manageable safety profile, including no drug-drug interactions and no Boxed Warnings for QTc prolongation or Torsades de Pointes – key advantages for patients on multiple concurrent medications.”

The most common adverse reactions (≥20%) included elevated liver enzymes, infection, electrolyte abnormalities, fatigue, nausea, edema, and differentiation syndrome. KOMZIFTI carries a Boxed Warning for differentiation syndrome but not for QTc prolongation or Torsades de Pointes.

Takeyoshi Yamashita, executive vice president and chief medical officer at Kyowa Kirin, added: “In AML, where many patients face severe disease progression and limited treatment options, the evolution toward targeted therapies such as KOMZIFTI represents a major step forward and offers potential to transform existing standards of care.”

Kura and Kyowa Kirin formed a global partnership in 2024 to co-develop and commercialize KOMZIFTI. Kura will lead development and commercialization in the US, while Kyowa Kirin will oversee activities outside the US.