FDA Approves Axatilimab-csfr 9 mg and 22 mg Vial Sizes for cGVHD

The FDA has approved axatilimab-csfr (Niktimvo; Incyte and Syndax Pharmaceuticals) in 9 mg and 22 mg vial sizes for the treatment of chronic graft-versus-host disease (cGVHD) after failure of at least 2 prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs). The approved dose of axatilimab-csfr follows the August 2024 FDA approval for the treatment of cGVHD in a similar patient population, marking the drug as the first and only approved prescription treatment for cGVHD that targets colony stimulating factor 1 receptor (CSF-1R) to reduce the drivers of inflammation and fibrosis.^1,2

Image credit: Andrii | stock.adobe.com

cGVHD occurs after an allogeneic stem cell transplant in around 42% of transplant recipients and impacts approximately 17,000 US individuals. Following a bone marrow tissue or cell transplant from a donor, the recipient's body recognizes the cells as foreign, which induces the cells to attack the recipient’s body. The chance of GVHD occurrence when the donor and recipient are related is around 35% to 45% and around 60% to 80% when the donor and recipient are unrelated. The study authors noted that nearly 50% of patients that develop cGVHD require at least 3 lines of treatment.^1,3

Axatilimab-csfr could mediate the disease processes involved in cGVHD as a high-affinity antibody that targets the CSF-1R — the signaling of which has been demonstrated to be the critical regulatory pathway in the expansion and infiltration of donor-derived macrophages.^1,2 The current approved dose of axatilimab-csfr is 0.3 mg/kg up to a maximum dose of 35 mg, administered as an intravenous (IV) infusion over 30 minutes every 2 weeks in adults and pediatric patients weighing at least 40 kg.¹

The initial approval for axatilimab-csfr was based on results from the randomized, open-label, multicenter AGAVE-201 trial (NCT04710576) that assessed 3 dosages of axatilimab-csfr in adult and pediatric patients with recurrent or refractory cGVHD who weigh at least 40 kg and have failed at least 2 prior lines of systemic therapy. Participants in the first cohort received axatilimab 0.3 mg/kg via IV every 2 weeks for up to 2 years; in the second cohort, participants received axatilimab 1 mg/kg IV every 2 weeks for up to 2 years; and in the third cohort, participants received axatilimab 3 mg/kg IV every 4 weeks for up to 2 years.^1,2

The results demonstrated that the overall response rate (ORR) was 75% (95% CI: 64, 84) in the 79 patients treated with the recommended dosage of 0.3 mg/kg (up to a maximum dose of 35 mg) as an IV infusion over 30 minutes every 2 weeks until disease progression or unacceptable toxicity. Additionally, the median time to first response was 1.5 months (range: 0.9 to 5.1), with a median DOR of 1.9 months (95% CI: 1.6, 3.5). No new deaths or new systemic therapy initiation were reported in 60% (95% CI: 43, 74) of patients that achieved response during the trial for at least 12 months following response to therapy, according to study authors.^1,2

The most common (≥ 15%) adverse effects patients reported during the trial 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.^1,2

"As the first and only FDA-approved anti-CSF-1R antibody targeting the drivers of inflammation and fibrosis in chronic GVHD, Niktimvo represents a major breakthrough for patient care," said Michael Metzger, Chief Executive Officer, Syndax, in a news release.¹

The launch of axatilimab-csfr in 9 mg and 22 mg vial sizes is expected in early February 2025.¹

REFERENCES

1. Incyte and Syndax Announce U.S. Food and Drug Administration (FDA) Approval of Niktimvo™ (axatilimab-csfr) 9 mg and 22 mg Vial Sizes. PR Newswire. News release. January 15, 2025. Accessed January 16, 2025. https://www.prnewswire.com/news-releases/incyte-and-syndax-announce-us-food-and-drug-administration-fda-approval-of-niktimvo-axatilimab-csfr-9-mg-and-22-mg-vial-sizes-302352411.html.

2. Hippensteele A. FDA Approves Axatilimab-csfr for cGVHD. Pharmacy Times. News release. August 12, 2024. Accessed January 16, 2025. https://www.pharmacytimes.com/view/fda-approves-axatilimab-csfr-for-cghvd.

3. Graft Versus Host Disease (GVH). Penn Medicine. April 29, 2022. Accessed January 16, 2025. https://www.pennmedicine.org/for-patients-and-visitors/patient-information/conditions-treated-a-to-z/graft-versus-host-disease.