Syndax Prescribed drugs has received FDA approval for a drug addressing superior instances of acute leukemia carrying a specific genetic signature that results in an aggressive type of the illness. The regulatory choice makes the Syndax drug the primary remedy in a brand new class of medicines for blood cancers.
The FDA approval particularly covers the remedy of adults and kids age 1 and older. The Syndax drug, a twice-daily tablet identified in growth as revumenib, can be marketed underneath the model identify Revuforj. The product’s late Friday approval got here six weeks forward of the goal date for a regulatory choice.
In leukemia, the proliferation of irregular white blood cells prevents bone marrow from producing crimson blood cells and platelets. Chemotherapy is a typical remedy. Blood transfusions don’t remedy the illness, however they’ll enhance a affected person’s ranges of crimson blood cells and platelets.
Waltham, Massachusetts-based Syndax designed Revuforj to inhibit a protein referred to as menin. In sufferers who’ve a rearrangement of the KMT2A gene, menin prompts pathways that drive most cancers progress. This specific genetic rearrangement drives an estimated 10% of acute leukemias, Syndax stated in an investor presentation. Sufferers whose most cancers carries this genetic signature have poor prognoses and excessive charges of drug resistance and relapse. Revuforj is a small molecule that blocks the interplay of menin with KMT2A fusion proteins.
Syndax evaluated Revuforj in a single-arm, open-label Section 1/2 examine that enrolled 104 contributors, each adults and pediatric sufferers. Outcomes confirmed that remedy led to finish remission or full remission with partial hematologic restoration in 21.2% of examine contributors. The median length of the response was 6.4 months. Syndax stated 23% (24 out of 104) of sufferers within the examine underwent stem cell transplants after remedy with Revuforj. This process can restore a affected person’s skill to supply blood cells. Outcomes from the examine have been revealed in August within the Journal of Scientific Oncology. The corporate stated extra information will offered subsequent month in the course of the annual assembly of the American Society of Hematology.
Revuforj’s label carries a black field warning for the chance of differentiation syndrome, a complication through which a most cancers drug triggers an extreme immune response from the affected leukemia cells. Differentiation syndrome can grow to be deadly if it results in failure of key organs, reminiscent of the guts. In keeping with the Revuforj’s label, if differentiation syndrome is suspected, clinicians ought to begin corticosteroid remedy and monitor the affected person’s blood circulation and coronary heart till signs resolve.
“The FDA approval of the primary menin inhibitor is a significant breakthrough for sufferers with [relapsed/refractory] acute leukemia with a KMT2A translocation, a genetic alteration related to a really poor prognosis,” Dr. Ghayas Issa, affiliate professor of leukemia at The College of Texas MD Anderson Most cancers Middle,” stated in Syndax’s announcement of the approval. “The numerous scientific profit and sturdy efficacy seen with Revuforj represents a considerable enchancment over what has been traditionally noticed in these sufferers with beforehand out there therapies and has the potential to be an necessary new remedy choice for sufferers.”
Whereas Revuforj is now the primary FDA-approved menin inhibitor, potential rivals are on its heels. Kura Oncology has reached the Section 2 portion of a Section 1/2 take a look at of ziftomenib (previously KM-539) in superior acute myeloid leukemia. Icovamenib, a menin inhibitor from Biomea Fusion, is in early scientific growth in each liquid and strong tumors. Different firms creating small molecule menin inhibitors embrace Johnson & Johnson, Sumitomo Dainippon, and Daiichi Sankyo.
In the meantime, Syndax is working extra research that would help increasing Revuforj to make use of as an earlier line of remedy for leukemia characterised by a KMT2A translocation in addition to for leukemias pushed by a genetic mutation to mNPM1 gene, which is present in about 30% of acute myeloid leukemia instances. Final week, Syndax reported constructive preliminary Section 2 information in acute myeloid leukemia pushed by mNPM1. Within the first half of 2025, the corporate it plans to publish and current these outcomes at a medical convention and search FDA approval on this indication.
Syndax has priced Revuforj at $39,500 a month, which works out to $474,000 yearly earlier than any rebates or reductions. Dosing of Revuforj is in response to a affected person’s weight. The corporate stated it expects the 110 mg and 160 mg tablets of the drug will grow to be out there later this month by means of specialty distributors and specialty pharmacies. The bottom dose, 25 mg, is for sufferers who weigh lower than 40 kg (about 88 kilos). Syndax expects this dose will grow to be commercially out there subsequent yr, both late within the first quarter or early within the second quarter. Till then, Syndax will provide an oral answer of this dose through an expanded entry program.
Revuforj is the second FDA-approved product in latest months for Syndax. In August, the company accepted the antibody drug Niktimvo as a remedy for graft-versus-host illness. Niktimvo was developed in collaboration with Incyte. The companions are sharing in commercialization of the drug within the U.S.; Incyte holds unique commercialization rights to the product in the remainder of the world.
Photograph: Getty Pictures, Sarah Silbiger
