The U.S. Food and Drug Administration (FDA) has approved Niktimvo (axatilimab) for the treatment of chronic graft-versus-host disease (cGvHD) in adult and pediatric patients weighing at least 40 kg after failure of at least two prior lines of systemic therapy. This approval marks a significant advancement in the treatment of cGvHD, offering a novel mechanism of action for patients with limited therapeutic options. Niktimvo, developed by Syndax Pharmaceuticals and co-commercialized with Incyte in the U.S., is a first-in-class anti-colony stimulating factor-1 receptor (CSF-1R) antibody.
Mechanism of Action
Axatilimab, the active ingredient in Niktimvo, is a humanized immunoglobulin G4 monoclonal antibody that targets CSF-1R expressed on monocytes and macrophages. By inhibiting CSF-1R, axatilimab reduces the levels of circulating proinflammatory and profibrotic monocytes, as well as monocyte-derived macrophages. This action blocks the activity of harmful macrophages within tissues, addressing key drivers of inflammation and fibrosis observed in cGvHD.
AGAVE-201 Clinical Trial
The FDA's approval was based on the results of the AGAVE-201 Phase II clinical trial, a global, open-label, randomized, multicenter study. The trial enrolled 241 adult and pediatric patients with recurrent or refractory active cGvHD who had received at least two prior lines of systemic therapy. Patients were randomized to receive one of three distinct Niktimvo dose levels: 0.3 mg/kg every two weeks, 1 mg/kg every two weeks, or 3 mg/kg every four weeks, across a 28-day treatment cycle for up to two years. The primary endpoint was the objective response rate (ORR), as determined by the 2014 National Institutes of Health Consensus Criteria for cGvHD, by cycle 7 day 1.
The results of the AGAVE-201 trial, recently published in The New England Journal of Medicine, demonstrated that the trial met its primary endpoint across all dose cohorts. Patients in the 0.3 mg/kg every two weeks cohort (n=80) achieved the highest overall response rate (ORR) of 74% within the first six months of treatment (95% CI: 63-83). The median time to response was 1.7 months (range: 0.9-8.1). Among the patients who had a response in the 0.3 mg/kg dose cohort, an estimated 60% of patients maintained a response at 12 months.
Clinical Impact and Expert Commentary
"Niktimvo is the first FDA approved treatment that targets the disease-modifying macrophages involved in both the fibrotic and inflammatory processes driving chronic GVHD," said Pablo J. Cagnoni, M.D., President and Head of Research and Development at Incyte. "Following the launch of this new medicine, clinicians will be able to offer patients an agent that targets a distinct pathway and has demonstrated broad and durable responses in patients with chronic GVHD who progressed after at least two prior lines of therapy."
Daniel Wolff, M.D., Ph.D., Head, Senior Physician, and Professor at University Hospital Regensburg, commented, "Results from the AGAVE-201 trial show rapid, durable responses in all organs studied and patient subgroups, with clinically meaningful symptom burden reduction reported by most of these heavily-pretreated patients who had not responded to previous lines of treatment."
Adverse Events
The most common treatment-emergent adverse events (TEAEs) were consistent with the on-target effects of CSF-1R inhibition. TEAEs in greater than 20% of patients in the overall population (n=239) include transient laboratory abnormalities of increases in aspartate aminotransferase (AST), blood creatine kinase, lipase, lactate dehydrogenase, and alanine aminotransferase (ALT), as well as fatigue, and infections. In the 0.3 mg/kg dose cohort, grade ≥3 adverse events were reported in 49% of patients, with 6% experiencing TEAEs leading to discontinuation of treatment.
Commercialization and Availability
In the United States, Niktimvo will be co-commercialized by Incyte and Syndax Pharmaceuticals. Incyte has exclusive commercialization rights for Niktimvo outside of the U.S. The Companies anticipate launching Niktimvo in the U.S. no later than early first quarter 2025.
