On August 14, the U.S. Food and Drug Administration (FDA) approved axatilimab-csfr (Niktimvo), a colony-stimulating factor–1 receptor–blocking antibody, for the treatment of chronic graft-vs-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg.
AGAVE-201
Efficacy was evaluated in AGAVE-201 (ClinicalTrials.gov identifier NCT04710576), a randomized, open-label, multicenter trial investigating three dosages of axatilimab in adult and pediatric patients with recurrent or refractory chronic GVHD who had received at least two lines of systemic therapy and required additional treatment.
The major efficacy outcome measure was overall response rate through cycle 7 day 1, where overall response included complete or partial response according to the 2014 National Institutes of Health Consensus Development Project on Response Criteria. The overall response rate was 75% (95% confidence interval [CI] = 64%–84%) in the 79 patients treated with the recommended dosage. The median time to first response was 1.5 months (range = 0.9–5.1 months). The median duration of response, calculated from first response to disease progression, death, or new systemic therapies for chronic GVHD, was 1.9 months (95% CI = 1.6–3.5 months). In patients who achieved response, no death or new systemic therapy initiation occurred in 60% (95% CI = 43%–74%) of patients for at least 12 months since response.
The most common adverse reactions, including laboratory abnormalities, which occurred in ≥ 15% of patients who received axatilimab were 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.
The recommended axatilimab-csfr dose in patients who weigh at least 40 kg is 0.3 mg/kg, up to a maximum dose of 35 mg, as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review. Axatilimab-csfr was granted Orphan Drug and Fast Track designation for the treatment of chronic GVHD.
