The U.S. Food and Drug Administration (FDA) has expanded the approval of Niktimvo (axatilimab-csfr) to include 9 mg and 22 mg vial sizes, offering a new option for patients with chronic graft-versus-host disease (GVHD) who have failed at least two prior lines of systemic therapy. This approval, announced by Incyte and Syndax Pharmaceuticals, builds upon the initial approval of Niktimvo in August 2024 and marks a significant advancement in the treatment of chronic GVHD.
Niktimvo is the first and only FDA-approved therapy that targets colony stimulating factor-1 receptor (CSF-1R) to address the underlying inflammation and fibrosis associated with chronic GVHD. The drug's approval is based on data from the AGAVE-201 trial, a global, dose-ranging study that demonstrated a significant proportion of patients achieved a response within six months of treatment.
AGAVE-201 Trial Results
The AGAVE-201 trial evaluated the efficacy, safety, and tolerability of Niktimvo in 241 adult and pediatric patients with recurrent or refractory chronic GVHD. Patients were randomized into three cohorts receiving different doses of Niktimvo: 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks, or 3.0 mg/kg every four weeks. The primary endpoint was the proportion of patients achieving an objective response within six months.
The results showed that 75% of participants receiving 0.3 mg/kg every two weeks achieved a response within six months. Furthermore, 60% of participants maintained their response after one year of treatment, and 56% achieved a ≥7-point improvement in the modified Lee Symptom Scale score.
Safety and Tolerability
While Niktimvo demonstrated promising efficacy, the AGAVE-201 trial also highlighted potential adverse events. Forty-four percent of patients experienced serious adverse events (AEs), including infections and respiratory failure. Approximately 10% of patients discontinued treatment due to AEs, and 8% required a dose reduction. Common adverse reactions included increased liver enzymes (aspartate aminotransferase and alanine aminotransferase), decreased phosphate and hemoglobin, viral infection, musculoskeletal pain, and fatigue.
Clinical Significance
Chronic GVHD is a serious complication of allogeneic stem cell transplantation, where donor cells attack the recipient's organs. It is estimated that approximately 42% of transplant recipients develop chronic GVHD, affecting around 17,000 patients in the U.S. Nearly 50% of these patients require at least three lines of treatment, highlighting the need for additional effective therapies.
"As the first and only FDA-approved anti-CSF-1R antibody targeting the drivers of inflammation and fibrosis in chronic GVHD, Niktimvo represents a major breakthrough for patient care," said Michael Metzger, CEO of Syndax Pharmaceuticals. Hervé Hoppenot, CEO of Incyte, added, "Our deep understanding of chronic GVHD and our connections in the clinical community will support a successful launch, in partnership with Syndax, of this important medicine for patients."
Dosage and Availability
The approved dose of Niktimvo is 0.3 mg/kg, up to a maximum of 35 mg, administered as an intravenous infusion over 30 minutes every two weeks for adults and pediatric patients weighing at least 40 kg. Incyte and Syndax plan to make Niktimvo available in early February through a network of specialty distributors. They also offer the IncyteCARES program to assist eligible patients with access, education, and financial support.
Ongoing Research
Axatilimab is currently being investigated in Phase 2 and Phase 3 trials in combination with other therapies for chronic GVHD, including ruxolitinib and steroids. It is also being studied in a Phase 2 trial for idiopathic pulmonary fibrosis, expanding its potential therapeutic applications.
