Seventy-five percent of patients responded. That is the result from the AGAVE-201 trial that carried axatilimab-csfr (Niktimvo) to FDA approval on August 14, 2024, for chronic graft-versus-host disease (cGVHD) in people who have already failed other treatments.
The approval covers adults and children weighing at least 88.2 lbs whose disease progressed after at least 2 prior systemic therapies. Axatilimab is a colony stimulating factor (CSF)-1 receptor inhibitor, and it is the first drug of its kind for the condition. Incyte and Syndax announced the decision.
The condition
Chronic GVHD is a severe complication of allogeneic stem cell transplantation. Donor immune cells attack the recipient’s tissues and damage organs. AJMC described it as the leading cause of significant illness and death after such a transplant. About 42% of transplant recipients face GVHD, and half of them need more than one treatment regimen.
The trial numbers
AGAVE-201 tested three doses of axatilimab in adults and children with severe, recurrent cGVHD who had already had at least 2 prior lines of therapy. Efficacy was measured by overall response rate, which counts complete and partial responses.
Among 79 patients on the recommended dose, 75% had responded by day 1 of cycle 7 (95% CI, 64%-84%). The median time to a first response was 1.5 months. The median duration of response was 1.9 months. At least 12 months passed without treatment escalation or death for 60% of patients (95% CI, 43-74%).
Daniel Wolff, head of the GVHD Center at the University Hospital Regensburg, said he was encouraged by the responses “across all organs and patient subgroups” in a heavily pre-treated group. He said he looks forward to “a new and differentiated treatment option for my patients.”
Safety
Serious adverse events hit 44% of the 79 treated patients. Infection, viral infection and respiratory failure were the common ones. Ten percent permanently stopped the drug because of adverse events, 8% needed a lower dose, and 44% had doses interrupted, mostly for infections, musculoskeletal pain and fever.
Frequent adverse reactions were infection, fatigue, musculoskeletal pain, nausea, headache, diarrhea, cough, fever and shortness of breath. Lab abnormalities touching the liver, pancreas, kidneys and blood were also common.
Dosing and launch
The recommended dose is 0.3 mg/kg, capped at 35 mg, given as a 30-minute intravenous infusion every 2 weeks until the disease progresses or toxicity becomes unacceptable.
Hervé Hoppenot, Incyte’s chief executive, said patients whose disease progressed now have “a new treatment option with a novel mechanism of action.” To cut waste, Incyte and Syndax will ask the FDA to approve smaller vials than the 50 mg one now cleared. The US launch is expected in early 2025, pending that clearance.
