Ziftomenib Granted Breakthrough Therapy Designation by FDA in R/R AML

A novel treatment for certain patients with relapsed or refractory acute myeloid leukemia has received a Breakthrough Therapy Designation by the FDA.

The Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to the investigational drug ziftomenib for the treatment of patients with relapsed or refractory (R/R) NPM1-mutant acute myeloid leukemia (AML), according to an announcement from ziftomenib manufacturer Kura Oncology, Inc.

Breakthrough Therapy Designation, as explained on the FDA’s website, “is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).”

According to the announcement from Kura Oncology, ziftomenib is the first investigational treatment to receive Breakthrough Therapy Designation for the treatment of NPM1-mutant AML. The Breakthrough Therapy Designation comes nearly five years after the agency granted ziftomenib an Orphan Drug Designation for the treatment of AML.

“We are highly encouraged by FDA’s decision to grant Breakthrough Therapy Designation to ziftomenib, recognizing its potential as an innovative medicine for patients with relapsed/refractory NPM1-mutant AML,” stated Troy Wilson, president and chief executive officer of Kura Oncology, in the company’s news release. “NPM1-mutant AML represents approximately 30% of new AML cases annually, and this designation reflects that NPM1-mutant AML is a disease of significant unmet need for which there is no approved targeted therapy as well as the fact that ziftomenib offers potential to demonstrate substantial improvement over available therapies. We remain committed to bringing ziftomenib to the market as quickly as possible and look forward to working more closely with FDA to bring our ziftomenib program to patients in urgent need of effective treatments.”

The American Cancer Society reported that approximately 62,770 new cases and 23,670 deaths from leukemia will arise in 2024. Approximately 20,800 will be cases of AML, with about 11,220 deaths from AML, the majority being adults.

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The FDA, according to Kura Oncology, granted Breakthrough Therapy Designation to ziftomenib based on results from the ongoing KOMET-001 clinical trial, with the manufacturer reporting that treatment with a 600-milligram oral daily dose of standalone ziftomenib resulted in a 35% complete remission rate (the disappearance of all signs of cancer) among 20 patients with NPM1-mutant AML.

With approximately 199 participants, the study is currently recruiting for its second phase, according to its listing on clinicaltrials.gov. The company stated that it expects to complete enrollment by mid-2024.

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Ziftomenib prevents the interaction of two proteins, menin and KMT2A/MLL. If joined, they are responsible for the survival and proliferation of some leukemia cells, according to Kura Oncology’s website. The site notes that blocking this process allows cancerous juvenile cells to mature into healthy white blood cells.

According to the manufacturer, ziftomenib is also currently being evaluated for administration in combination with current standards of care. These include Venclexta (venetoclax)/azacitidine or cytarabine plus daunorubicin for patients with NPM1-mutant and KMT2A-rearranged AML in the KOMET-007 trial as well as with Xospata (gilteritinib), FLAG-IDA or LDAC among patients with NPM1-mutant and KMT2A-rearranged AML in the KOMET-008 clinical trial.

Researchers in KOMET-007 began dosing patients in 2023, while it was reported that the first patient was dosed in KOMET-008 in March.

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