U.S. FDA Approves Ziftomenib for Relapsed/Refractory AML

On Nov. 13, 2025, the United States Food and Drug Administration (FDA) approved ziftomenib (Komzifti, Kura Oncology and Kyowa Kirin), the first and only once-daily targeted therapy for adults with relapsed or refractory acute myeloid leukemia (AML) with NPM1 mutations.

AML is the most common type of leukemia in adults. About 1 in 3 people with AML have changes to the NPM1 gene. This mutation affects the part of the cell that helps cells divide, copy and repair DNA, and make proteins. It helps AML cells grow out of control. Around 20% of people with NPM1-mutated AML do not respond to initial treatments. For people with NPM1-mutated AML that returns after therapy (relapsed) or does not respond to treatment (refractory), treatment options are limited. Ziftomenib offers another treatment option for these patients. 

“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,” said Eunice Wang, MD at Roswell Park Comprehensive Cancer Center. “The clinical data demonstrate deep and durable responses with a manageable safety profile. [...] This approval equips physicians with a new oral therapy to integrate into care and improve outcomes for this vulnerable patient population.”

What is ziftomenib, and how does it treat AML?

Ziftomenib is a type of cancer medication called a menin inhibitor. In healthy cells, a protein called menin stops cells from growing and dividing. In NPM1-mutated AML, menin fuses with another protein called MLL. This causes the leukemia cells to grow out of control. Menin inhibitors keep these proteins apart, helping the bone marrow produce healthy white blood cells. Ziftomenib is taken as a once-daily oral medication. The goal of ziftomenib is to restore normal cell development in the bone marrow and slow the progression of AML.

The study that led to ziftomenib approval

The Phase 2 KOMET-001 study included 92 adults with relapsed or refractory NPM1-mutated AML. Participants were heavily pretreated, and many had received prior therapies such as venetoclax (Venclexta, AbbVie) or undergone stem cell transplantation.

Results showed a complete remission (CR) of 23%. Among those who responded, 67% achieved minimal residual disease (MRD) negativity. MRD negativity means no measurable leukemia was found using highly sensitive testing. 

What are the common side effects of ziftomenib? 

Ziftomenib was generally well tolerated. Only 3% of participants needed to discontinue therapy due to side effects. The most common serious event was differentiation syndrome. This is a known complication when leukemia cells begin to mature in response to therapy. It happened to 13% of participants, but it was manageable.

Importantly, investigators reported low levels of myelosuppression (reduced bone marrow activity) and no clinically meaningful QTc prolongation. This is a heart rhythm concern seen with some AML therapies. These findings suggest a safety profile that may allow people to maintain a higher quality of life while receiving care.

Next steps for people living with AML 

If you or a loved one has AML, ask your healthcare team about how your current treatment is working for you and if ziftomenib or ongoing studies can be a next step. Visit the Kura Oncology website or explore HealthTree for AML for educational resources and clinical trial listings.

Questions to ask your care team about ziftomenib

1. Has my leukemia been tested for NPM1 mutations?
2. Would a menin inhibitor like ziftomenib be appropriate for my type of AML?
3. What side effects should I be aware of, and how can they be managed?
4. How is differentiation syndrome monitored and treated if it occurs?
5. Could I be eligible for any clinical trials using ziftomenib in combination with other therapies?

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Sources: 

• Ziftomenib in relapsed/refractory (R/R) NPM1-mutant acute myeloid leukemia (AML): Phase 1b/2 clinical activity and safety results from the pivotal KOMET-001 study.
• FDA approves ziftomenib for relapsed or refractory acute myeloid leukemia with a NPM1 mutation
• Kura Oncology and Kyowa Kirin Announce FDA Approval of KOMZIFTI™ (ziftomenib), the First and Only Once-Daily Targeted Therapy for Adults with Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia