FDA Approves Axatilimab for Chronic Graft-vs-Host Disease

The FDA approved axatilimab-csfr (Niktimvo) for the treatment of adult and pediatric patients weighing at least 40 kg with chronic graft-vs-host disease (cGVHD) who have progressed on at least 2 prior lines of systemic therapy.¹

The regulatory decision was supported by findings from the randomized, open-label, multicenter, phase 2 AGAVE-201 trial (NCT04710576), which evaluated 3 dose levels of axatilimab in adult or pediatric patients with recurrent or refractory cGVHD who had received 2 or more lines of systemic therapy and required additional treatment.

Axatilimab—a colony stimulating factor-1 receptor (CSF1-R)–blocking antibody—elicited an overall response rate (ORR) through cycle 7, day 1 of 75% (95% CI, 64%-84%) among 79 patients who received the recommended dosage of the agent. The median time to first response was 1.5 months (range, 0.9-5.1). The median duration of response (DOR), calculated from first response to progression, death, or next systemic therapy for cGVHD, was 1.9 months (95% CI, 1.6-3.5). No death or new systemic therapy initiation occurred in 60% (95% CI, 43%-74%) of responders for at least 12 months after response.

The recommended dose of axatilimab 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 administered over 30 minutes every 2 weeks until disease progression or unacceptable toxicity.

The most common adverse effects occurring in at least 15% of patients, including laboratory abnormalities, 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 AGAVE-201 Trial

AGAVE-201 enrolled allogeneic hematopoietic stem cell transplantation recipients at least 2 years of age with active cGVHD requiring systemic immune suppression.² Active cGVHD was defined as the presence of signs and symptoms of cGVHD per the 2014 National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in cGVHD.

Eligible patients needed to have refractory or recurrent cGVHD following at least 2 lines of systemic therapy. Patients were permitted to have persistent, active, acute, and cGVHD manifestations or overlap syndrome. Patients needed to have a Karnofsky performance state of at least 60 if 16 years of age or older, or a Lanksky performance status of at least 60 if younger than 16 years of age.

Patients were excluded if they had acute GVHD without manifestations of cGVHD; any evidence of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening; a history of acute or chronic pancreatitis; a history of myositis; or a history or other evidence of uncontrolled infection, severe illness, or any other conditions that would make them unsuitable for the trial per investigator opinion. Prior treatment with any CSF1-R–targeted therapies was not allowed.

Patients received intravenous axatilimab at 1 of 3 dose levels: 0.3 mg/kg every 2 weeks for up to 2 years, 1 mg/kg every 2 weeks for up to 2 years, or 3 mg/kg every 4 weeks for up to 2 years.

ORR served as the trial's primary end point. Secondary end points included the number of patients with a clinically significant improvement in normalized score on the modified Lee Symptom Scale, DOR, sustained response rate, organ-specific response rate, and safety.

References

1. FDA approves axatilimab-csfr for chronic graft-versus-host disease. FDA. August 14, 2024. Accessed August 14, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease
2. A study of axatilimab at 3 different doses in participants with chronic graft versus host disease (cGVHD) (AGAVE-201). ClinicalTrials.gov. Updated June 14, 2024. Accessed August 14, 2024.