FDA Approves Axatilimab for Chronic Graft-Versus-Host Disease

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has approved axatilimab-csfr (Niktimvo) for the treatment of chronic graft-versus-host disease (cGVHD), after failure of prior systemic therapy in adult and pediatric patients weighing >40 kg.¹

Announced by the FDA on August 14, 2024, approval was awarded based on findings from the randomized, open-label, multicenter Phase 2 AGAVE-201 trial. AGAVE-201 investigated 3 dosages of axatilimab, a colony-stimulating factor-1 receptor-blocking antibody, in those with recurrent or refractory cGVHD who failed ≥2 prior lines of systemic therapy.

The Phase 2 trial’s primary efficacy outcome measure was the overall response rate (ORR) through Cycle 7 Day 1 – overall response included complete or partial response, according to the 2014 National Institutes of Health (NIH) Consensus Development Project on Response Criteria.²

Overall, the ORR was 75% (95% CI, 64–84) among 79 patients treated with the recommended axatilimab dosage, with a median time to first response of 1.5 months (range, 0.9–5.1).¹ Further analysis revealed the median duration of response was 1.9 months (95% CI, 1.6–3.5), defined as the time from the first response to progression, death, or initiation of new systemic therapies.

Among individuals with chronic GVHD who achieved response, AGAVE-201 results demonstrated no death or initiation of new systemic therapy in approximately 60% (95% CI, 43–74) of patients for ≥12 months since response.

Safety data showed serious adverse reactions occurred in 44% of patients who received axatilimab, with permanent discontinuation in 10% and dose reduction due to adverse reactions in 8% of patients.

The most common (≥15%) adverse reactions were increased aspartate aminotransferase (AST), infection, increased alanine aminotransferase (ALT), decreased phosphate, decreased hemoglobin, viral infection, increased gamma-glutamyl transferase (GGT), musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase (CPK), increased alkaline phosphatase (ALP), nausea, headache, diarrhea, cough, bacterial infection, pyrexia, and dyspnea.¹

“I am excited that Niktimvo 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," said Daniel Wolff, MD, PhD, head of the GVHD Center at the University Hospital Regensburg.³ "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.”

Axatilimab’s recommended dosage for patients who weigh ≥40 kg is 0.3 mg/kg, up to a maximum dose of 35 mg.¹ The therapy is administered as an intravenous infusion over 30 minutes every 2 weeks until the progression of disease or unacceptable toxicity.

The Biologics License Application (BLA), submitted by Incyte Corporation, was granted Priority Review by the FDA and used the agency’s Assessment Aid to facilitate regulatory assessment. Axatilimab was also granted Orphan Drug Designation and Fast Track Designation for the treatment of cGVHD.

In the US, axatilimab will be co-commercialized by Incyte and Syndax Pharmaceuticals.³ After FDA approval of axatilimab as a 50mg vial, the companies will seek approval to launch two smaller vial sizes to enable patient dosing and reduce product waste. Pending FDA approval of the new vial sizes, the companies anticipate axatilimab's launch in the US by the first quarter of 2025.

References

1. _{Center for Drug Evaluation and Research. FDA approves Axatilimab-CSFR for chronic graft-versus-host disease. U.S. Food and Drug Administration. 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. June 14, 2024. Accessed August 14, 2024. https://www.clinicaltrials.gov/study/NCT04710576.}
3. _{Incyte and Syndax announce U.S. FDA approval of NiktimvoTM (Axatilimab-CSFR) for the treatment of chronic graft-versus-host disease (GVHD). Incyte. August 14, 2024. Accessed August 15, 2024. https://investor.incyte.com/news-releases/news-release-details/incyte-and-syndax-announce-us-fda-approval-niktimvotm-axatilimab}