Last reviewed 2026-04-20 · How we verify

Komzifti (ZIFTOMENIB)

Komzifti works by inhibiting the menin protein, which is involved in the regulation of gene expression in cancer cells.

Komzifti (ziftomenib) is a small molecule menin inhibitor developed by Kura, targeting relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation. It is a patented medication with no generic manufacturers available. Komzifti was FDA-approved in 2025 for its approved indications. The bioavailability of Komzifti is 12.9%. Key safety considerations are not specified in the provided facts.

At a glance

Mechanism of action

Ziftomenib is a menin inhibitor that blocks the interaction of menin and lysine [K]-specific methyltransferase 2A (KMT2A). Acute leukemias can be driven by mutations in NPM1 that recruit the wild-type menin-KMT2A complex to promoters of leukemogenic genes. Susceptible NPM1 mutations are defined as those that result in loss of the nucleolar localization signal and the insertion of a new nuclear export signal leading to cytoplasmic accumulation of mutant NPM1 protein that disrupts normal cell function and drives leukemogenesis through altered gene expression. Pharmacologic disruption of the menin-KMT2A protein-protein interaction by ziftomenib blocks oncogenic activity of mutant NPM1, which induces differentiation of leukemic cells as evidenced by increased expression of differentiation markers. In nonclinical studies, ziftomenib demonstrated in vitro and in vivo antitumor activity in models of NPM1 -mutant leukemia.

Approved indications

• relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation
• relapsed or refractory acute myeloid leukemia (AML) with a susceptible nucleophosmin 1 (NPM1) mutation

Boxed warnings

• WARNING: DIFFERENTIATION SYNDROME Differentiation syndrome, which can be fatal, has occurred with KOMZIFTI. Signs and symptoms may include fever, joint pain, hypotension, hypoxia, dyspnea, rapid weight gain or peripheral edema, pleural or pericardial effusions, pulmonary infiltrates, acute kidney injury, and rashes. If differentiation syndrome is suspected, interrupt KOMZIFTI and initiate oral or intravenous corticosteroids with hemodynamic and laboratory monitoring until symptom resolution; resume KOMZIFTI upon symptom improvement [see Dosage and Administration ( 2.5 ), Warnings and Precautions ( 5.1 ), and Adverse Reactions ( 6.1 )] . WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning. Differentiation syndrome, which can be fatal, has occurred with KOMZIFTI. If differentiation syndrome is suspected, interrupt KOMZIFTI and initiate oral or intravenous corticosteroids with hemodynamic and laboratory monitoring until symptom resolution; resume KOMZIFTI upon symptom improvement. ( 2.5 , 5.1 , 6.1 )

Common side effects

• Infection without an identified pathogen
• Differentiation syndrome
• Febrile neutropenia
• Bacterial infection
• Hemorrhage
• Diarrhea
• Nausea
• Fatigue
• Edema
• Musculoskeletal pain
• Transaminases increased
• Aspartate aminotransferase increased

Drug interactions

• Strong or Moderate CYP3A4 Inhibitors
• Strong or Moderate CYP3A4 Inducers
• Proton Pump Inhibitors
• H2 Receptor Antagonists and Antacids
• Drugs that Prolong the QTc Interval
• Ziftomenib
• Gastric Acid Reducing Agents
• Locally acting antacids
• H2 receptor antagonists (H2RAs)
• Other product(s) with a known potential to prolong the QTc interval
• CYP3A4 Inhibitors
• CYP3A4 Inducers

Key clinical trials

• Ziftomenib Maintenance Post Allo-HCT (PHASE1)
• Ziftomenib for the Treatment of Patients With NPM1 Mutated or KMT2A Rearranged Acute Myeloid Leukemia Not Eligible for Standard Therapy (PHASE2)
• A Study to Investigate the Safety and Tolerability of Ziftomenib in Combination With Venetoclax/Azacitidine, Venetoclax, 7+3, or 7+3+Quizartinib in Patients With AML (PHASE1)
• Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML (PHASE3)
• Phase 1/1b Trial Of Olutasidenib And Ziftomenib For NPM1 And IDH1 Co-Mutated Acute Myeloid Leukemia (PHASE1)
• Dose Escalation and Expansion of Ziftomenib in Combination With Quizartinib in Acute Myeloid Leukemia (PHASE1)
• A Study of Ziftomenib in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) (PHASE1)
• A Phase I Study Investigating the Combination of the Ziftomenib, Venetoclax and Azacitidine in Pediatric Relapsed and Refractory Acute Leukemias (PHASE1)

Patents

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Komzifti CI brief — competitive landscape report
• Komzifti updates RSS · CI watch RSS
• Kura portfolio CI