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The FDA approved the colony stimulating factor-1 receptor (CSF-1R) inhibitor axatilimab (Niktimvo) for chronic graft-versus-host-disease (cGVHD) that has failed two prior lines of systemic therapy.

The allows use in adults and pediatric patients weighing at least 40 kg. Incyte received the biologics license for the monoclonal antibody.

Support for approval came primarily from the AGAVE-201 trial that evaluated three dosages of axatilimab in patients with recurrent/refractory cGVHD previously treated with at least two prior lines of systemic therapy. The primary outcome was overall response rate (ORR) through day 1 of cycle 7, which included complete and partial response the 2014 NIH Consensus Development Project on Response Criteria.

The results showed a 75% ORR in 79 patients who received the recommended dose of 0.3 mg/kg. Median time to response was 1.5 months, and median response duration was 1.9 months. Subsequently, 60% of responding patients survived at least 12 months with no new systemic therapy for cGVHD.

Adverse reactions occurring in ≥15% of patients consisted of increased aspartate aminotransferase, infection (pathogen unspecified), increased alanine aminotransferase, decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase, musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase, increased alkaline phosphatase, nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea.

CSF-1R-dependent monocytes and macrophages play a key role in cGVHD inflammation and fibrosis.

"Axatilimab, with its unique mechanism of action, may represent a new therapeutic strategy in chronic graft-versus-host disease," said Daniel Wolff, MD, PhD, of the University Hospital Regensburg in Germany, late last year at the American Society of Hematology meeting, "The highest overall response rate and the least toxicity was observed with the lowest dose, and that underlines the crucial importance of sufficiently powered studies in this vulnerable patient population."

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