Revumenib

While specific treatment options for the roughly one-third of AML patients with NPM1 mutations have historically been limited, Syndax Pharmaceuticals broke new ground in late October when the FDA cleared its drug Revuforj as the first menin inhibitor in the indication. Kyowa Kirin’s big bet on Kura Oncology has paid off in short order, delivering an FDA approval for a medicine to treat a subset of patients with acute myeloid leukemia.On Thursday, the FDA signed off on Kura’s menin inhibitor ziftomenib as a new treatment for adults with relapsed or refractory acute myeloid leukemia (AML) who have a susceptible nucleophosmin 1 (NPM1) mutation. To qualify for the treatment, which will be marketed under the brand name Komzifti, patients must not be a good fit for any alternative treatments, the FDA said in a Nov. 13 approval announcement.While specific treatment options for the roughly one-third of AML patients with NPM1 mutations have historically been limited, Syndax Pharmaceuticals broke new ground in late October when the FDA cleared its drug Revuforj as the first menin inhibitor in the indication. Syndax’s drug was originally approved last November to treat a genetic type of leukemia called lysine methyltransferase 2A (KMT2A).The two meds, both members of the same class, will now likely compete directly over the indication.NPM1 mutations rank among the most common founder mutations in AML, Kura and Kyowa Kirin said in a joint press release Thursday. Roughly 20% of patients with NPM1-m AML do not respond to frontline therapy, and of those who do, some 70% will relapse within three years, according to the partners. The FDA granted its green light after reviewing data from the partners’ pivotal KOMET-001 trial, in which 21.4% patients on Komzifti achieved complete remission (CR) or CR with partial hematologic recovery (CRh), Kura and Kyowa Kirin said in their release. The median duration of remission among those who achieved CR or CRh clocked in at 5 months, the partners said. Further, 88% of patients who hit either CR or CRh did so within half a year of starting treatment with Komzifti, Kura and Kyowa Kirin added.Komzifti will carry a boxed warning for differentiation syndrome—a potentially severe reaction to certain leukemia treatments—though patients and doctors applying more scrutiny to which drugs they prescribe alongside Komzifti can ease those potential risks, according to the companies’ approval announcement. The drug also bears precautions around QTc interval prolongation and embryo-fetal toxicity.Syndax’s Revuforj label bears similar warnings and precautions, with its boxed warnings discussing risks of differentiation syndrome, QTc prolongation and the fast heart rhythm condition Torsades de Pointes.The safety profile of Kura and Kyowa's drug "overall looks a bit better" than that for Revuforj, analysts at Mizuho Securities concluded, adding that a differentiation syndrome boxed warning for the menin inhibitor class comes as "[n]o real surprise." “Komzifti combines compelling efficacy, a favorable safety profile, compatibility with concomitant medications, and convenient once-daily oral administration in a population with few effective treatment options,” Troy Wilson, Ph.D., CEO of Kura, said in a statement. “These features highlight Komzifti’s potential to serve as the menin inhibitor of choice in its approved indication.”Kyowa Kirin hitched its wagon to Kura and ziftomenib just shy of a year ago, paying $330 million upfront in November 2024—and pledging up to $1.1 billion in potential milestones—to split development and commercialization on the asset.Under the deal, Kura is in charge of development, regulatory and commercial strategy for Komzifti in the U.S., as well as manufacturing, while Kyowa Kirin is holding down R&D and marketing duties outside the U.S. In their press release, the partners said that following the approval, they will now “jointly perform certain commercialization activities in accordance with a co-created U.S. territory commercialization plan.”Kura’s stock was trading up around 1% on Thursday morning. Editor's note: This story was updated to clarify information on Komzifti's label, and to include analyst commentary. 

The FDA gave the go-ahead to Kura Oncology and Kyowa Kirin’s treatment for certain acute myeloid leukemia patients, just weeks after a rival drug was approved for a similar population. Thursday’s approval is the first for ziftomenib, which will be branded as Komzifti. The drug is cleared for use in adult patients with NPM1-mutated acute myeloid leukemia whose disease has returned or stopped responding to treatment and who have no good alternative options. The US list price for a one-month supply of Komzifti is $48,500, Kura told Endpoints News . Komzifti blocks a cell growth protein called menin, on which researchers believe this type of AML is dependent. There are roughly 22,000 people in the US diagnosed with AML each year, according to the American Cancer Society, and roughly a third of those cases bear NPM1 mutations. On Oct. 24, Syndax Pharmaceuticals won approval for its menin inhibitor Revuforj in AML with NPM1 mutations. However, there are some differences between the approval of Kura and Kyowa Kirin’s drug, which they are jointly commercializing in the US, and the FDA nod for Revuforj. Syndax’s drug came with a black box warning for differentiation syndrome, QTc prolongation and Torsades de Pointes. Differentiation syndrome is a known complication of leukemia treatment, while the latter two are serious heart activity abnormalities. Kura’s drug also comes with a black box warning for differentiation syndrome, but a less alarming warning on QTc prolongation. In addition, Kura’s drug was approved for adults only, while Syndax’s drug was approved for children and adults. Komzifti was approved on data from a Phase 1/2 trial called KOMET-001 that showed it led to a 21.4% complete remission rate with full or partial blood count recovery in 112 patients. The approval came more than two weeks ahead of the FDA’s deadline of Nov. 30.