FDA Approves Axatilimab-csfr for Chronic Graft-vs-Host Disease

Axatilimab-csfr is now approved for adults and children with chronic graft-versus-host disease after at least 2 prior lines of treatment. | Image Credit: Tada Images - stock.adobe.com

The FDA approved axatilimab-csfr (Niktimvo), a colony stimulating factor (CSF)-1 receptor inhibitor, for treating chronic graft-versus-host disease (cGVHD) in adults and children weighing at least 88.2 lbs.¹ This treatment is indicated for patients who have progressed on at least 2 prior systemic therapies.

The decision was supported by the AGAVE-201 (NCT04710576) trial, which evaluated 3 axatilimab doses in adults and children with severe, recurrent cGVHD who required further treatment after at least 2 prior lines of therapy.

“I am excited that [axatilimab] is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pre-treated population enrolled in the AGAVE-201 trial,” Daniel Wolff, MD, PhD, head of the GVHD Center at the University Hospital Regensburg, said in a statement.² “I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.”

Chronic GVHD is a severe complication arising after allogeneic stem cell transplantation when donor immune cells attack recipient tissues, leading to organ damage. This condition is the leading cause of significant morbidity and mortality following an allogeneic stem cell transplant.

Approximately 42% of transplant recipients face the challenge of GVHD, with half of these patients requiring multiple treatment regimens. This highlights the urgent need for novel therapeutic approaches.

The AGAVE-201 trial assessed efficacy based on overall response rate (ORR), comprising complete and partial responses.¹ Among 79 patients receiving the recommended dose, 75% achieved ORR by day 1 of cycle 7 (95% CI, 64%-84%). Median time to first response was 1.5 months (range, 0.9-5.1) with a median duration of 1.9 months (95% CI, 1.6-3.5). Notably, 60% of patients (95% CI, 43-74%) remained response-free without treatment escalation or death for at least 12 months.

Serious adverse events (SAEs) affected 44% of the 79 patients who were treated with axatilimab.² Common SAEs included infection, viral infection, and respiratory failure. There were 10% of patients who permanently discontinued axatilimab due to adverse events, while 8% required dose reduction. Dose interruptions occurred in 44% of patients, primarily due to viral infection, unspecified infection, bacterial infection, musculoskeletal pain, and fever.

Frequent adverse reactions included infection, fatigue, musculoskeletal pain, nausea, headache, diarrhea, cough, fever, and shortness of breath.¹ Laboratory abnormalities were also common, affecting liver enzymes, pancreas, kidney function, blood, and other markers.

The recommended dosage for axatilimab in patients who weigh at least 88.2 lbs is 0.3 mg/kg, with a maximum dose of 35 mg, as an intravenous infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity.

“With the approval of [axatilimab], patients with chronic GVHD whose disease has progressed after prior therapies, now have a new treatment option with a novel mechanism of action to help address the serious and devastating complications associated with this disease,” said Hervé Hoppenot, chief executive officer at Incyte.²

To optimize dosing and reduce waste, Incyte and Syndax will seek FDA approval for smaller axatilimab vials following the 50 mg vial approval. The new drug is anticipated to launch in the US in early 2025, pending FDA clearance of the new vial sizes.

References

1. FDA approves axatilimab-csfr for chronic graft-versus-host disease. News release. FDA. August 14, 2024. Accessed August 15, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease

2. Incyte and Syndax announces U.S. FDA approval of Niktimvo (axatilimab-csfr) for the treatment of chronic graft-versus-host disease (GVHD). News release. Syndax. August 14, 2024. Accessed August 15, 2024. https://ir.syndax.com/news-releases/news-release-details/incyte-and-syndax-announce-us-fda-approval-niktimvotm-axatilimab