FDA Approves Ziftomenib: First Once-Daily Oral Therapy for Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia

Ziftomenib, sold under the brand name Komzifti, is a new oral medicine approved to treat adults with a type of blood cancer called acute myeloid leukemia (AML). It’s meant for people whose AML has come back or hasn’t responded to other treatments and who have a specific genetic change called an NPM1 mutation. This mutation is one of the most common in AML, found in about one-third of newly diagnosed cases.

Ziftomenib is the first once-daily oral medicine in a new class called menin inhibitors. It works by blocking a protein called menin, which helps leukemia cells grow in people with NPM1 mutations. By stopping this protein, the medicine decreases cancer cell growth and stops the cells from multiplying.

This approval is important because people with relapsed or treatment-resistant AML often have few options and poor outcomes. Many live only a few months after trying several treatments.

In studies, the medicine helped people across different age groups and genetic backgrounds, showing deep and lasting responses. This makes it a meaningful new option for a group of people who urgently need better treatments.

Why Was It Approved?

Ziftomenib was approved based on results of a study in adults with relapsed or treatment-resistant AML that had an NPM1 mutation. In the study, about 1 in 4 people had their cancer go into complete remission or near-complete remission. Overall, about 1 in 3 people responded to the medicine. Some of those who responded also had no signs of cancer left in their blood, which suggests a deeper response.

People who responded to the medicine started seeing results in about two to three months, though some needed a little longer. Among those who responded, the average survival time was over 18 months, which is much longer than the average of about six months for all the people in the study.

These results are especially meaningful because many people in the study have already tried several other treatments, including stem cell transplants and venetoclax.

What Do I Need to Know?

You take ziftomenib by mouth once a day on an empty stomach, ideally at the same time each day. If you miss a dose, take it as soon as you remember – unless it’s close to your next dose. Don’t take two doses too close together.

Before starting treatment, your health care provider will check your heart rhythm with an electrocardiogram (EKG) and test your blood for potassium and magnesium levels. These checks help lower the risk of a heart rhythm problem called QTc prolongation. If you were born with a heart rhythm condition or take other medicines that affect your heart, you may need more frequent monitoring.

One serious side effect to watch for is differentiation syndrome, a condition where leukemia cells change too quickly and cause inflammation. This can happen as early as three days after starting treatment. It causes symptoms like a fever, trouble breathing, swelling, or chest pain. If you notice any of these, contact your health care provider right away. There are treatments that can help manage this condition.

Only a small number of people, about 2 to 4 out of 100, stopped taking the medicine because of side effects. No deaths were directly linked to the medicine.

Ziftomenib is not safe to use during pregnancy or while breastfeeding. It may harm a fetus, so women should use effective birth control during treatment and for six months after the last dose. You should also avoid breastfeeding while taking the medicine and for at least two weeks after your last dose.

The medicine has shown a good safety profile, even in older adults. It causes less bone marrow suppression than some other treatments and rarely leads to stopping treatment.