Syndax Pharmaceuticals has won FDA approval for a drug addressing advanced cases of acute leukemia carrying a particular genetic signature that leads to an aggressive form of the disease. The regulatory decision makes the Syndax drug the first therapy in a new class of medicines for blood cancers.
The FDA approval specifically covers the treatment of adults and children age 1 and older. The Syndax drug, a twice-daily pill known in development as revumenib, will be marketed under the brand name Revuforj. The product’s late Friday approval came six weeks ahead of the target date for a regulatory decision.
In leukemia, the proliferation of abnormal white blood cells prevents bone marrow from producing red blood cells and platelets. Chemotherapy is a standard treatment. Blood transfusions do not cure the disease, but they can boost a patient’s levels of red blood cells and platelets.
Waltham, Massachusetts-based Syndax designed Revuforj to inhibit a protein called menin. In patients who have a rearrangement of the KMT2A gene, menin activates pathways that drive cancer growth. This particular genetic rearrangement drives an estimated 10% of acute leukemias, Syndax said in an investor presentation. Patients whose cancer carries this genetic signature have poor prognoses and high rates of drug resistance and relapse. Revuforj is a small molecule that blocks the interaction of menin with KMT2A fusion proteins.
Syndax evaluated Revuforj in a single-arm, open-label Phase 1/2 study that enrolled 104 participants, both adults and pediatric patients. Results showed that treatment led to complete remission or complete remission with partial hematologic recovery in 21.2% of study participants. The median duration of the response was 6.4 months. Syndax said 23% (24 out of 104) of patients in the study underwent stem cell transplants after treatment with Revuforj. This procedure can restore a patient’s ability to produce blood cells. Results from the study were published in August in the Journal of Clinical Oncology. The company said more data will presented next month during the annual meeting of the American Society of Hematology.
Revuforj’s label carries a black box warning for the risk of differentiation syndrome, a complication in which a cancer drug triggers an excessive immune response from the affected leukemia cells. Differentiation syndrome can become fatal if it leads to failure of key organs, such as the heart. According to the Revuforj’s label, if differentiation syndrome is suspected, clinicians should start corticosteroid therapy and monitor the patient’s blood circulation and heart until symptoms resolve.
“The FDA approval of the first menin inhibitor is a major breakthrough for patients with [relapsed/refractory] acute leukemia with a KMT2A translocation, a genetic alteration associated with a very poor prognosis,” Dr. Ghayas Issa, associate professor of leukemia at The University of Texas MD Anderson Cancer Center,” said in Syndax’s announcement of the approval. “The significant clinical benefit and robust efficacy seen with Revuforj represents a substantial improvement over what has been historically observed in these patients with previously available therapies and has the potential to be an important new treatment option for patients.”
While Revuforj is now the first FDA-approved menin inhibitor, potential competitors are on its heels. Kura Oncology has reached the Phase 2 portion of a Phase 1/2 test of ziftomenib (formerly KM-539) in advanced acute myeloid leukemia. Icovamenib, a menin inhibitor from Biomea Fusion, is in early clinical development in both liquid and solid tumors. Other companies developing small molecule menin inhibitors include Johnson & Johnson, Sumitomo Dainippon, and Daiichi Sankyo.
Meanwhile, Syndax is running additional studies that could support expanding Revuforj to use as an earlier line of treatment for leukemia characterized by a KMT2A translocation as well as for leukemias driven by a genetic mutation to mNPM1 gene, which is found in about 30% of acute myeloid leukemia cases. Last week, Syndax reported positive preliminary Phase 2 data in acute myeloid leukemia driven by mNPM1. In the first half of 2025, the company it plans to publish and present these results at a medical conference and seek FDA approval in this indication.
Syndax has priced Revuforj at $39,500 a month, which works out to $474,000 annually before any rebates or discounts. Dosing of Revuforj is according to a patient’s weight. The company said it expects the 110 mg and 160 mg tablets of the drug will become available later this month through specialty distributors and specialty pharmacies. The lowest dose, 25 mg, is for patients who weigh less than 40 kg (about 88 pounds). Syndax expects this dose will become commercially available next year, either late in the first quarter or early in the second quarter. Until then, Syndax will supply an oral solution of this dose via an expanded access program.
Photo: Getty Images, Sarah Silbiger
