Axatilimab Gets Priority Review for Chronic Graft-vs-Host Disease

The Food and Drug Administration (FDA) has accepted for Priority Review the Biologics License Application for axatilimab for the treatment of graft-vs-host-disease (GVHD) after failure of at least 2 prior lines of systemic therapy.

Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor. The application is supported by data from the phase 2 AGAVE-201 study (ClinicalTrials.gov Identifier: NCT04710576), which evaluated the safety and efficacy of axatilimab in 241 adult and pediatric patients with recurrent or refractory active GVHD whose disease had progressed after 2 therapies. Prior treatments included ruxolitinib (74%), ibrutinib (31%) and belumosudil (23%).

Study participants were randomly assigned to 1 of 3 treatment groups: 0.3mg/kg every 2 weeks, 1mg/kg every 2 weeks, or 3mg/kg every 4 weeks. The primary endpoint was overall response rate (ORR) defined as the proportion of patients in each dose group who achieved an objective response based on 2014 NIH Consensus Criteria for chronic GVHD by cycle 7 day 1.

Findings showed patients receiving 0.3mg/kg every 2 weeks had the highest ORR, 74% (95% CI, 63-83), within the first 6 months of treatment. Median time to response in this cohort was 1.7 months (range, 0.9-8.1); 60% of these patients maintained a response at 12 months. 

In the 0.3mg/kg dose group, 55% of patients achieved at least a 7-point improvement in the modified Lee Symptom Scale score (secondary endpoint). Additionally, organ specific responses were observed across all organs involved at baseline, with notable responses in fibrosis-dominated organs: esophagus (78%), joints and fascia (76%), lungs (47%), and skin (27%).

The most common treatment-emergent adverse events reported were increases in aspartate aminotransferase, blood creatine phosphokinase, lipase, lactate dehydrogenase, and alanine aminotransferase.

“Despite recent advancements in the treatment of patients with chronic GVHD, there remains a significant unmet need for patients who progressed on earlier lines of therapy,” said Hervé Hoppenot, CEO , Incyte. “Axatilimab’s novel mechanism offers a differentiated treatment approach which may help patients suffering from this devastating disease. We look forward to working closely with the FDA and our partners at Syndax on the review of our application for axatilimab for this indication.”

A Prescription Drug User Fee Act date of August 28, 2024 has been set for the application.