FDA Approves Komzifti for NPM1-Mutant Acute Myeloid Leukemia

The U.S. Food and Drug Administration (FDA) has approved Komzifti (ziftomenib), which is a type of treatment known as a menin inhibitor, for use in adults with relapsed or refractory acute myeloid leukemia (AML) with a susceptible NPM1 mutation who have no satisfactory alternative treatment options.

The approval was announced in a notice issued by the FDA.

The effectiveness of the treatment was shown, according to the notice from the agency, in the KO-MEN-001 open-label, single arm, multicenter trial of 112 adults with relapsed or refractory AML with an NPM1 mutation, with its effectiveness established based on rates of complete remission (CR) plus CR with partial hematological recovery (CRh), the duration of CR plus CRh and the rate of conversion from transfusion dependence to transfusion independence.

At a median follow-up of 4.2 months, the CR plus CRh rate was 21.4% and the duration of CR plus CRh was five months. The agency further reported that the CR rate was 17% and the CRh rate was 4.5%. Additionally, among 66 patients who were depended on red blood cell and/or platelet transfusions at baseline, 14, or 21.2%, became transfusion independent during any 56-day post-baseline period, and of the 46 patients who were independent of both red blood cell and platelet transfusions at baseline, 12, or 26.1%, remained transfusion independent during any 56-day post-baseline period.

The FDA stated in its notice of the approval that the prescribing information of the drug includes warnings and precautions for differentiation syndrome, QTc interval prolongation and embryo-fetal toxicity, with the recommended dose being 600 milligrams taken orally once a day until disease progression or unacceptable toxicity.

What is Komzifti and how does it work?

Komzifti, as it is defined by the National Cancer Institute on its website, is designed to prevent the interaction between the proteins menin and MLL, prohibiting the formation of the menin-MLL complex, hence reducing the expression of downstream target genes and resulting in an inhibition of the proliferation of MLL-rearranged leukemic cells. The menin-MLL complex, according to the National Cancer Institute, plays a key role in the survival, growth and proliferation of certain kinds of leukemia cells.

According to the National Cancer Institute, the drug is being evaluated in a dozen clinical trials currently. In addition to acute myeloid leukemia, this includes clinical trials for patients with cancer types such as gastrointestinal stromal tumors, acute lymphoblastic leukemia and acute lymphocytic leukemia.

In September, data that were touted by Kura Oncology and Kyowa Kirin as pivotal regarding Komzifti in patients with relapsed/refractory NPM1-mutant acute myeloid leukemia were published in The Journal of Clinical Oncology.

“Relapsed or refractory NPM1-mutated AML remains very challenging to treat, particularly after [Venclexta (venetoclax)]-based therapy or transplant,” said Dr. Eunice Wang, Chief of Leukemia Service, Professor of Oncology, Roswell Park Comprehensive Cancer Center in Buffalo, New York, in a news release issued at the time. “The manuscript describes deep responses, signals of clinical activity across relevant subgroups and a generally manageable tolerability profile, which is important in treatment of late line AML patients where accumulated toxicity can limit treatment options. The benefit-risk profile of [Komzifti] is highly encouraging and, if replicated in additional treatment settings, has potential to be transformative for a large population of patients with menin pathway-driven AML.”

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