FDA Grants First-in-Class Approval to Syndax's Leukemia Drug

Syndax Pharmaceuticals has achieved a significant milestone with the FDA approval of its drug, Revuforj, designed to treat advanced cases of acute leukemia that exhibit a specific genetic marker associated with aggressive forms of the disease. This approval makes Revuforj the pioneering therapy in a new class of blood cancer medicines.

Revuforj, formerly known as revumenib during its development, is a twice-daily oral medication approved for use in adults and children aged one year and older. The FDA's Friday decision came notably six weeks before the anticipated target date. This drug specifically targets leukemia patients with a rearrangement of the KMT2A gene, which activates menin and consequently promotes cancer growth. This genetic rearrangement is responsible for approximately 10% of acute leukemia cases, often resulting in poor prognosis and high relapse and drug resistance rates. Revuforj works by inhibiting the interaction between menin and KMT2A fusion proteins.

The drug's efficacy was assessed in a Phase 1/2 study involving 104 participants, including both adults and children, in a single-arm, open-label trial. The results revealed that 21.2% of participants achieved complete remission or complete remission with partial hematologic recovery, with the median response duration being 6.4 months. Additionally, 23% of patients treated with Revuforj proceeded to undergo stem cell transplants, which can help restore the production of blood cells. These findings were published in the Journal of Clinical Oncology, and more detailed data is expected to be presented during the American Society of Hematology's annual meeting.

Revuforj's FDA label includes a black box warning due to the risk of differentiation syndrome, a serious complication where a cancer drug induces an excessive immune response from leukemia cells, potentially leading to the failure of vital organs like the heart. Medical professionals are advised to initiate corticosteroid therapy and monitor blood circulation and heart function if differentiation syndrome is suspected.

Dr. Ghayas Issa from The University of Texas MD Anderson Cancer Center highlighted the significance of this approval, stating that the introduction of the first menin inhibitor marks a major breakthrough for patients with relapsed or refractory acute leukemia possessing a KMT2A translocation. He emphasized the considerable clinical benefits and efficacy of Revuforj compared to previously available treatments, suggesting that it could become an essential new treatment option for these patients.

While Revuforj is currently the only FDA-approved menin inhibitor, other potential competitors are advancing in their development. Kura Oncology is progressing with a Phase 2 trial of ziftomenib in advanced acute myeloid leukemia, while Biomea Fusion's icovamenib is undergoing early clinical trials for both liquid and solid tumors. Additional companies like Johnson & Johnson, Sumitomo Dainippon, and Daiichi Sankyo are also developing small molecule menin inhibitors.

Syndax is conducting further studies to potentially expand Revuforj’s use as an earlier treatment option for leukemia involving the KMT2A translocation and leukemias driven by mutations in the mNPM1 gene, which is present in around 30% of acute myeloid leukemia cases. Recently, Syndax announced promising preliminary Phase 2 data for acute myeloid leukemia with mNPM1 mutations, with plans to present the results and seek FDA approval in this indication by the first half of 2025.

Revuforj is priced at $39,500 per month, equating to an annual cost of $474,000 before discounts or rebates. The dosing of Revuforj is weight-based, with 110 mg and 160 mg tablets expected to be available later this month through specialty distributors and pharmacies. The lowest dose, 25 mg, intended for patients under 40 kg (88 pounds), is anticipated to be commercially available next year, either late in the first quarter or early in the second quarter. In the interim, Syndax will provide an oral solution of this dose through an expanded access program.