The U.S. Food and Drug Administration (FDA) has approved ziftomenib, a new oral medication for patients suffering from acute myeloid leukemia (AML), one of the deadliest forms of blood cancer. This approval specifically targets individuals with recurring or treatment-resistant AML who possess a mutation in the NPM1 gene. The drug, which is taken once daily, offers a vital treatment option for patients who have limited alternatives.
The research leading to this breakthrough began at the University of Virginia School of Medicine in 2007, spearheaded by Jolanta Grembecka, Ph.D., and Tomasz Cierpicki, Ph.D. Both researchers initially served as assistant professors in the Department of Molecular Physiology and Biological Physics at UVA, where they collaborated closely with their former postdoctoral mentor, John Bushweller, Ph.D. In 2009, Grembecka and Cierpicki transitioned to the University of Michigan, where they currently hold professorships in the Department of Pathology.
Dr. Mark Esser, head and chief scientific officer of UVA’s Paul and Diane Manning Institute of Biotechnology, highlighted the significance of this achievement, stating, “Ziftomenib is a long-awaited and desperately needed new option for patients for whom other treatments have failed.” He emphasized that the Manning Institute was established to advance critical research aimed at developing new treatments for complex diseases.
Understanding Acute Myeloid Leukemia
Acute myeloid leukemia is particularly aggressive and primarily affects individuals over the age of 68. According to the American Cancer Society, more than 22,000 Americans are diagnosed with AML each year, resulting in over 11,000 deaths. This disease represents about one-third of all blood cancer cases, underscoring the urgent need for effective treatments.
Grembecka noted the challenges associated with AML, stating, “Acute myeloid leukemia is a very aggressive blood cancer with poor clinical outcomes.” She expressed her satisfaction in witnessing their pioneering research on menin inhibitors evolve into an FDA-approved treatment. “This is an achievement we could only dream of, and now it’s a reality,” she added.
The foundational discoveries made by Grembecka and Cierpicki were licensed to Kura Oncology in 2014. Ziftomenib was developed in collaboration with Kura and is marketed under the brand name Komzifti in partnership with the pharmaceutical group Kyowa Kirin. The drug functions by disrupting the interactions of the cellular protein menin, which drives the growth and survival of leukemia cells, allowing them to mature into healthy white blood cells instead of becoming cancerous.
Cierpicki explained the extensive work required to develop menin inhibitors, stating, “To develop menin inhibitors, we had to pioneer an entirely new area of research.” This included producing human proteins, developing biochemical assays, conducting high-throughput screening, and solving the crystal structure of menin, all at a time when skepticism in the pharmaceutical industry regarding targeting protein-protein interactions was prevalent.
Clinical Trials and Future Implications
The journey to FDA approval for ziftomenib began with clinical trials commencing in 2019. The urgency for a new treatment option was acknowledged by the FDA, which granted the drug a priority review. Bushweller, part of the UVA Comprehensive Cancer Center, remarked on the impact of this research: “Their success portends a future with more such targeted agents and successes that dramatically improve cancer care.”
Ongoing clinical trials are currently investigating the potential of ziftomenib to enhance treatment in combination with other therapies for both leukemia and solid tumors. Dr. Esser emphasized the importance of accelerating drug development, stating, “Many patients don’t have time to wait.” The Manning Institute is dedicated to developing new treatments efficiently and safely to ensure timely access for patients.
Esser concluded, “It’s always exciting to see UVA research produce important new options such as ziftomenib for patients. Now we are positioned to make that happen faster.” This approval marks a significant step forward in the fight against acute myeloid leukemia, offering renewed hope to those affected by this challenging disease.
