Komzifti

Komzifti is used to treat relapsed or refractory acute myeloid leukemia (AML) in adults with a nucleophosmin 1 (NPM1) mutation with no other satisfactory alternative treatment options. It is taken once daily and should be taken for a minimum of 6 months unless there is disease progression or unacceptable toxicity.

Komzifti (ziftomenib) gained FDA approval on November 13, 2025.

Take Komzifti exactly as your healthcare provider tells you to

• Take once daily at approximately the same time each day
• Take on an empty stomach: at least 1 hour before or 2 hours after meals
• Swallow capsules whole. Do not open, break, or chew
• Do not change your dose or stop taking it without consulting your doctor.

If you take medicine to reduce stomach acid:

• Avoid taking a proton pump inhibitor (PPI) medicine with Komzifti
• Take Komzifti either 2 hours before or 10 hours after taking an H2 receptor blocker medicine.
• Take Komzifti either 2 hours before or 2 hours after taking a locally acting antacid medicine (such as calcium carbonate).

Before taking Komzifti, tell your healthcare provider about all your medical conditions, including it you:

• Have heart problems or long QT syndrome
• Have electrolyte imbalances (abnormal potassium or magnesium levels)
• Are pregnant or planning a pregnancy
• Are breastfeeding or planning to breastfeed.

Tell your healthcare provider about all medications you take, including prescription drugs, over-the-counter medicines, vitamins, and herbal supplements.

Komzifti is not approved for use in children.

Warnings

Komzifti carries a Boxed Warning for differentiation syndrome, a potentially life-threatening inflammatory complication to anticancer medications.

Differentiation Syndrome

Komzifti can cause differentiation syndrome, a life-threatening condition affecting blood cells. This syndrome can occur as early as 3 days after starting treatment or later during therapy. See your healthcare provider immediately if you develop symptoms of differentiation syndrome, which may include:

• Fever
• Joint or bone pain
• Dizziness
• Shortness of breath or difficulty breathing
• Cough
• Chest pain
• Rapid weight gain
• Rash
• Decreased urinary output
• Swelling in the hands, feet, ankles, or legs.

Common side effects

The most common side effects of Komzifti are:

• Infection without an identified pathogen
• Severe bleeding (hemorrhage)
• Diarrhea
• Nausea
• Fatigue
• Swelling in arms and legs (edema)
• Bacterial infection
• Musculoskeletal pain
• Differentiation syndrome
• Itching (pruritus)
• Fever with low white blood cell count (febrile neutropenia)
• Increased liver transaminases.

Serious side effects

Komzifti may cause the following serious side effects.

QTc interval prolongation

Komzifti can cause changes in heart electrical activity (QTc prolongation), leading to potentially fatal irregular heartbeats. Your doctor will monitor your heart with ECGs and check potassium and magnesium levels before and during treatment. Contact your doctor immediately if you experience:

• Fainting, lightheadedness, or dizziness
• Shortness of breath
• Irregular or rapid heartbeat.

In patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval, more frequent ECG monitoring may be necessary.

Birth Defects

Komzifti can harm an unborn baby when given to pregnant women.

• In animal studies, pregnant mice given ziftomenib during organ development experienced embryo-fetal death, birth defects, and abnormal fetal growth at doses approximately 0.3 times the human clinical exposure level.
• Pregnant women should be informed of these potential risks to the fetus.
• Women who can become pregnant should use effective contraception during Komzifti treatment and for 6 months after the final dose.
• Men with female partners who can become pregnant should also use effective contraception during treatment and for 3 months after the final dose.

Notes:

Komzifti may cause fertility problems in females and males, which may affect your ability to have children. Talk toyour healthcare provider if this is a concern for you.

This is not a complete list of side effects. Report side effects to your doctor or the FDA at 1-800-FDA-1088.

Komzifti (ziftomenib) works by blocking the interaction between menin and KMT2A (lysine-specific methyltransferase 2A) proteins. NPM1 mutations recruit the menin-KMT2A complex to promoters of leukemogenic genes, driving acute leukemia. By disrupting this protein interaction, ziftomenib stops the cancerous activity of mutant NPM1, inducing differentiation of leukemia cells and demonstrating antitumor activity in NPM1-mutant leukemia models.

Komzifti belongs to the drug class called menin inhibitors.

Adult Dose of Komzifti for AML

• 600 mg orally once daily.
• Continue until disease progression or unacceptable toxicity.
• For patients without confirmed disease progression or unacceptable toxicity, treat for a minimum of 6 months to allow time for a clinical response.

If you miss a dose of Komzifti or did not take it at the usual time, take your dose as soon as possible and at least12 hours before your next scheduled dose. Return to your normal schedule the following day.

Do not take 2 doses within 12 hours of each other to make up for the missed dose.

Komzifti can interact with several types of medications. Tell your healthcare provider about all drugs you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Especially tell your healthcare provider if you take:

• CYP3A4 inhibitors (avoid or monitor closely): Strong or moderate CYP3A4 inhibitors may increase Komzifti levels in your blood. Your doctor will monitor you more frequently for side effects. Examples: Ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice
• CYP3A4 inducers (avoid): These medications can decrease Komzifti's effectiveness. Avoid taking together. Examples: Rifampin, phenytoin, carbamazepine, St. John's wort
• Proton pump inhibitors/PPIs (avoid): PPIs significantly reduce Komzifti absorption. Do not take together. Examples: Omeprazole (Prilosec), esomeprazole (Nexium), lansoprazole (Prevacid), pantoprazole (Protonix)
• H2 blockers and antacids (separate dosing): If you must take these, timing is critical:
• H2 blockers: Take Komzifti 2 hours before or 10 hours after (examples: famotidine, ranitidine)
• Antacids: Take Komzifti 2 hours before or 2 hours after (examples: calcium carbonate, Tums, Maalox)
• QT-prolonging drugs (avoid or monitor): Medications that affect heart rhythm increase the risk of dangerous irregular heartbeats when combined with Komzifti. If unavoidable, your doctor will monitor your heart more frequently with ECGs. Examples: Azithromycin, ondansetron, haloperidol, amiodarone, sotalol, certain antipsychotics, and antidepressants

Keep a list of all your medications to show your healthcare provider and pharmacist.

Store at room temperature between 68°F and 77°F (20°C and 25°C).

Keep in the original container with its child-resistant cap and keep out of reach of children.

Active ingredient: Ziftomenib

Inactive ingredients: Croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, sodium lauryl sulfate

Capsule shell: Hypromellose, titanium dioxide, black ink.

Komzifti is available as 200 mg capsules.

Komzifti is manufactured for Kura Oncology, Inc., San Diego, CA 92121.