FDA approves Revuforj for AML with NPM1 mutations
Approval is second in less than a year for blood cancer treatment
The U.S. Food and Drug Administration (FDA) has approved Syndax‘s oral therapy Revuforj (revumenib) as a treatment for certain people with acute myeloid leukemia (AML) who have a susceptible mutation in the gene NPM1.
The FDA approval specifically covers Revuforj’s use in AML patients ages 1 and older whose disease is relapsed or refractory — meaning the cancer did not respond to or came back after previous treatments — and who do not have any satisfactory alternative treatment options available. This marks the second FDA approval for Revuforj, which was already approved to treat relapsed/refractory acute leukemia with certain mutations in another gene called KMT2A.
“We are thrilled to have secured a second indication for Revuforj, making it the first and only menin inhibitor that is FDA-approved for multiple acute leukemia subtypes in both adults and children,” Michael A. Metzger, CEO of Syndax, said in a company press release. “The breadth of the indicated patient population highlights the compelling and consistent efficacy and tolerability of Revuforj in multiple different types of patients. Our launch into this second population will greatly benefit from physicians’ already strong familiarity with Revuforj and positive experience treating well over 1,000 patients in clinical trials and nearly one year of commercial use.”
Revuforj designed to block interactions between 2 proteins
AML is an aggressive form of blood cancer. In roughly a quarter of AML cases, the NPM1 gene is mutated. These mutations lead to abnormal interactions between two proteins, KMT2A and menin, and these interactions are thought to drive cancer growth. Revuforj is designed to block the interactions between KMT2A and menin, thus inhibiting cancer growth.
The FDA’s approval of Revuforj for NPM1-mutant AML was based on data from the Phase 1/2 AUGMENT-101 clinical trial (NCT04065399), which tested the therapy in 64 adults with this form of blood cancer. Results showed nearly half of patients had a clinically meaningful response to treatment.
“The expanded FDA approval of Revuforj marks a major advancement in the management of acute leukemia patients,” said Joshua F. Zeidner, MD, chief of leukemia research at the University of North Carolina’s Lineberger Comprehensive Cancer Center. “For the first time, a targeted, oral therapy that is well tolerated and efficacious is approved for R/R [relapsed/refractory] NPM1 mutated AML and R/R KMT2A translocated acute leukemia. The compelling clinical activity observed with Revuforj in clinical trials and clinical practice paves the way for a new standard of care for these two aggressive and difficult-to-treat blood cancers.”
According to its prescribing information, the most common side effects of Revuforj in AML patients include bleeding, nausea, diarrhea, infections, fatigue, swelling, pain, constipation, reduced appetite, changes in heart rate, and abnormalities in various biomarkers and nutrient levels. The therapy also carries a boxed warning, the FDA’s most stringent safety warning, noting that it can cause life-threatening reactions, including abnormal heart rhythms or a blood cancer treatment complication called differentiation syndrome.
The FDA approval of a precision treatment that selectively targets the pathway driving this form of AML offers new hope to patients and their loved ones.
The oral therapy is taken twice daily, without food or with a low-fat meal. The dosage is determined depending on a patient’s weight and other medications.
The new FDA approval comes barely a month after the National Comprehensive Cancer Network, a nonprofit alliance of 33 cancer centers, issued guidelines backing Revuforj for use in hard-to-treat AML with NPM1 gene mutations. The approval was welcomed by advocates in the blood cancer community.
“New treatment options are vitally needed for patients with NPM1 mutated AML whose disease has returned or not improved after previous treatment,” said Lore Gruenbaum, PhD, chief scientific officer of Blood Cancer United (formerly The Leukemia and Lymphoma Society). “The FDA approval of a precision treatment that selectively targets the pathway driving this form of AML offers new hope to patients and their loved ones.”
For U.S. patients prescribed Revuforj, Syndax offers SyndAccess, a program that provides personalized support and resources — including financial assistance — for those who qualify.
About the Author
