A new drug has received U.S. Food and Drug Administration (FDA) approval, in which the Barbara Ann Karmanos Cancer Institute played a crucial role. The oral targeted menin inhibitor ziftomenib (known by its brand name Komzifti™) received FDA approval on Nov. 13, 2025. Ziftomenib is a once-daily oral targeted therapy for adult patients with nucleophosimin 1 (NPM1)-mutated acute myeloid leukemia (AML).
“AML is an aggressive blood and bone marrow cancer, and mutations in the NPM1 gene are among the most common genetic drivers of the disease in adult patients,” explained Suresh Balasubramanian, M.D., hematologist and medical oncologist, member of the Hematology Oncology Multidisciplinary Team and the Molecular Therapeutics Research Program at Karmanos. “Ziftomenib blocks the menin–KMT2A/NPM1 pathway, which leukemia cells rely on for survival, making it a highly precise treatment option for this molecular subtype.”
This therapy benefits patients with relapsed or refractory NPM1-mutated AML. Prior to this FDA approval, treatment options for these patients were extremely limited, with allogeneic stem cell transplantation being the only potentially curative choice—an option many patients could not pursue because of age, comorbidities or other contraindications. In addition, conventional therapy is often insufficient to treat the disease at this stage, but ziftomenib provides mutation-directed, targeted treatment.
“This approval represents a major milestone for patients with NPM1-mutated AML. For decades, AML treatment relied heavily on cytotoxic chemotherapy,” said Dr. Balasubramanian.
NPM1 mutations are the most common in AML, accounting for approximately 30% of cases, according to a press release from Kura Oncology, Inc., the company that developed Komzifti. Twenty percent of those patients’ cancers may not respond to first-line therapy, and 70% of those patients’ cancers may relapse within 12 months to three years. For a disease that has very few effective treatment options, ziftomenib makes receiving therapy easier for patients. No longer having to do chemotherapy, patients will take one pill once a day.
Dr. Balasubramanian was the principal investigator at Karmanos for three clinical trial studies of this new therapy, which led to FDA approval. This includes the phase I clinical trial study, “Ziftomenib in Relapsed or Refractory NPM1-Mutated AML” (published in the Journal of Clinical Oncology), where the drug was first investigated in humans, and the dosage of the drug was tested. Dr. Balasubramanian’s team continued patient studies, offering a phase II trial. Results from studies demonstrated a deep response. Now, Karmanos offers phase III combination clinical trials using this treatment.
“We continue to enroll and treat patients on multiple ongoing studies evaluating ziftomenib in various treatment settings and combinations, in addition to now being able to prescribe the FDA-approved therapy,” he described. “My research laboratory also conducted preclinical mechanistic and combination studies with ziftomenib even before the clinical trials started, and we continue to explore new scientific questions related to menin inhibition.”
As Dr. Balasubramanian described, this new targeted approach to treating NPM1-mutated AML represents a continued paradigm shift toward precision therapies tailored to the genetics of the leukemia.
“Ziftomenib adds an important new tool that has the potential to improve outcomes and expand treatment options for patients who previously had very limited therapies. We are proud that Karmanos played a meaningful role in bringing this therapy from early development to FDA approval,” Dr. Balasubramanian said.
Karmanos offers many clinical trials to treat blood cancers. They can be found in the Karmanos Clinical Trials Portal here.