FDA approves Kura Oncology leukemia drug to compete with Syndax Pharma
The FDA approved a Kura Oncology drug developed to target acute myeloid leukemia (AML) cases that carry a specific genetic signature, giving the biotech its first commercial asset and an opportunity to challenge Syndax Pharmaceuticals' product, which was the first to market among such targeted cancer therapies.
This emerging drug treats leukemia characterized by mutations in the NPM1 gene. Thursday's regulatory decision on Kura's drug ziftomenib covers the treatment of adults with relapsed or refractory AML with this profile and no other treatment options. San Diego-based Kura has partnered with Kyowa Kirin to commercialize its new once-daily pill under the Komzifti brand.
AML is a cancer of myeloid cells, the white blood cells that normally develop into normal blood cells in the bone marrow. NPM1 mutations are estimated to occur in 30% of AML cases. NPM1 is a gene that encodes a protein involved in a variety of cellular processes. Mutations in this gene cause protein abnormalities that lead to uncontrolled growth of immature white blood cells.
Komzifti does not act directly on NPM1 or its protein. The progression of acute leukemia may be driven by the interaction of NPM1 with a protein complex composed of menin and KMT2A. Kura's oral small molecule is designed to inhibit menin, blocking the protein's interaction with KMT2A.
The FDA's decision on Komzifti is full regulatory approval. The drug's submission is based on data from an open-label, single-arm Phase 2 study that enrolled 112 adults. The primary objectives were to measure the rate of complete response and the rate of complete response with partial hematologic recovery. The results showed the rate was 21.4%; the median duration of response was five months. Additionally, 88% of patients achieved complete remission or complete remission with partial hematologic recovery within six months of starting treatment with Kura. The results were published in September in the Journal of Clinical Oncology.
Komzifti's approval comes nearly a year after Syndax's Revuforj became the first FDA-approved menin inhibitor. The regulatory decision covers the treatment of acute leukemias characterized by KMT2A gene alterations in adults and children 1 year of age and older. Last month, the FDA approved label expansion of the drug to treat AML in adults and children 1 year and older who carry NPM1 mutations.
Kura aims to differentiate itself from Syndax's Revuforj, claiming patient convenience and greater safety. Komzifti is taken once a day compared to Revuforj which is taken orally twice a day. In terms of safety, both products carry a boxed warning about the risk of differentiation syndrome, a complication that occurs when cancer drugs trigger an excessive immune response from leukemia cells. Although differentiation syndrome can be fatal, it can be managed with corticosteroids and monitoring. But Revuforj's boxed warning also includes the risk of QTc prolongation, a type of irregular heartbeat, and torsade de pointes, an abnormally fast heart rhythm.
Kura CEO Troy Wilson said on a conference call Thursday that the same heart complications are included in the Komzifti label, but in the warnings and precautions section instead of a black box warning. Treatment-related adverse events are rare and manageable, said Dr. Eunice Wang, chief of the leukemia service at Roswell Park Comprehensive Cancer Center, professor of oncology and principal investigator of the Komzifti clinical trial. She also noted that the Komzifti label does not contain a warning about drug interactions. This is important because many people with leukemia also take other drugs, such as drugs that inhibit the liver enzyme CY3PA4, which can affect the exposure of anticancer drugs in the body.
“There are no drug-drug interactions, and ziftomenin is not associated with the black box warnings of QTc prolongation and torsade de pointes, which is a significant clinical benefit for our patients,” Wang said. “These patients are often taking multiple medications that may interact with CY3PA4 and/or prolong the QT interval. As a practicing clinician, if one can choose a menin that does not have the drug-drug interactions or black box warnings, inhibitors, then people would prioritize menin inhibitors with a better benefit-risk profile.”
One month's supply of Komzifti is $48,500. Chief commercial officer Brian Powl said the company expects the drug to be available within the next few business days. Kura expects the product to generate annual sales of $350 million to $400 million in the relapsed and refractory NPM1-mutated AML market. But Powl noted that the company is testing the drug as an early treatment option and in combination with other AML therapies. Data from these studies will be presented at the American Society of Hematology's annual meeting next month. In the frontline environment, Kura expects Komzifti's sales to reach $7 billion.
Kura will commercialize Komzifti through a collaboration with Kyowa Kirin that began last year. Under the agreement, Kura leads U.S. commercialization and is responsible for manufacturing the product. Kyowa Kirin will lead the development and commercialization of the drug outside the U.S.
Photo by Kula Oncology
