The U.S. Food and Drug Administration (FDA) has approved a new oral medication, ziftomenib, designed for patients suffering from acute myeloid leukemia (AML) who face recurring or treatment-resistant cases. This significant advancement originated from research at the University of Virginia School of Medicine and offers a vital treatment option for those with a mutation in the NPM1 gene, often leaving them with limited alternatives.
The development of ziftomenib is attributed to the efforts of researchers Jolanta Grembecka, Ph.D., and Tomasz Cierpicki, Ph.D., who began their work in 2007 while serving as research assistant professors at UVA’s Department of Molecular Physiology and Biological Physics. Both researchers later joined the University of Michigan as professors in the Department of Pathology.
In a statement, Mark Esser, Ph.D., head and chief scientific officer of UVA’s Paul and Diane Manning Institute of Biotechnology, highlighted the approval as a long-awaited achievement, particularly for patients with limited hope. “Ziftomenib is a wonderful achievement by Drs. Grembecka and Cierpicki,” he said. The Manning Institute was established to facilitate advances in critical research, aiming to accelerate the development of new treatments for complex diseases.
Understanding Acute Myeloid Leukemia
Acute myeloid leukemia is notably aggressive and primarily affects individuals over the age of 68. According to the American Cancer Society, over 22,000 Americans are diagnosed with AML each year, with more than 11,000 fatalities attributed to the disease. Grembecka remarked on the urgency of this new treatment, stating, “Acute myeloid leukemia is a very aggressive blood cancer with poor clinical outcomes.” The evolution of their research into an FDA-approved treatment is a significant milestone, transforming their years of work into a tangible benefit for patients.
The foundational discoveries made by Grembecka and Cierpicki were licensed to Kura Oncology in 2014. Ziftomenib was subsequently developed in collaboration with Kura and is marketed under the brand name Komzifti, in partnership with pharmaceutical group Kyowa Kirin. The drug functions by disrupting the interactions of menin, a protein that promotes the growth and survival of leukemia cells, allowing them to mature into healthy white blood cells instead.
Cierpicki explained the challenges faced in developing menin inhibitors, stating, “To develop menin inhibitors, we had to pioneer an entirely new area of research.” This included producing the human protein, creating robust biochemical assays, and solving the crystal structure of menin, all while the pharmaceutical industry remained skeptical about targeting protein-protein interactions.
The Path to FDA Approval
Ziftomenib’s path to FDA approval was expedited due to the pressing need for new treatment options. Clinical trials commenced in 2019, and the promising results led to the drug receiving a priority review from the FDA. “It is immensely gratifying to see the work of Drs. Grembecka and Cierpicki have this amazing impact for patients,” said John Bushweller, Ph.D., a member of the UVA Comprehensive Cancer Center.
Ongoing clinical trials are investigating the potential of ziftomenib in combination with other treatments, aiming to extend its efficacy to both leukemia and solid tumors. “Drug development has traditionally been a long and slow process,” Esser noted, emphasizing the urgency for timely solutions. The Manning Institute is dedicated to developing new treatments swiftly and safely to ensure that patients have access to necessary therapies.
Esser further expressed enthusiasm for the breakthrough, stating, “It’s always exciting to see UVA research produce important new options such as ziftomenib for patients.” The approval of ziftomenib marks a hopeful turning point in the fight against acute myeloid leukemia, offering renewed hope to those who previously had few alternatives.
