Axatilimab is an investigational monoclonal antibody that targets colony stimulating factor-1 receptor, or CSF-1R, a cell surface protein thought to control the survival and function of monocytes and macrophages. In pre-clinical models, inhibition of signaling through the CSF-1 receptor has been shown to reduce the number of disease-mediating macrophages along with their monocyte precursors, which has been shown to play a key role in the fibrotic disease process underlying diseases such as chronic graft-versus-host disease (GVHD) and idiopathic pulmonary fibrosis (IPF).
Chronic GVHD, an immune response of the donor-derived hematopoietic cells against recipient tissues, is a serious, potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation which can last for years. Chronic GVHD is estimated to develop in approximately 50% of transplant recipients and affects approximately 14,000 patients in the U.S.1,2 This disease typically manifests across multiple organ systems, with skin and mucosa being commonly involved, and is characterized by the development of fibrotic tissue.3
Late-Stage Clinical Development
In July 2023, Syndax and its partner, Incyte, announced positive topline data from the pivotal AGAVE-201 trial of axatilimab, Syndax’s anti-CSF-1R antibody, in patients with chronic GVHD following two or more prior lines of therapy. All three dose cohorts, 0.3 mg/kg every two weeks, 1.0 mg/kg every two weeks and 3.0 mg/kg every four weeks, met the primary endpoint. The overall response rate within the first six months of treatment at the 0.3 mg/kg dose was 74%, and 60% of these patients were still responding at one year. Furthermore, axatilimab was generally well tolerated, and the most common adverse events were consistent with on-target effects and prior trials.
Axatilimab was granted Orphan Drug Designation by the U.S. Food and Drug Administration for the treatment of patients with chronic GVHD and IPF. In September 2021, Syndax and Incyte entered into an exclusive worldwide co-development and co-commercialization license agreement for axatilimab. Axatilimab is being developed under an exclusive worldwide license from UCB entered into between Syndax and UCB in 2016.
To learn more about axatilimab, check out our publications page, including Phase 1/2 data in chronic GVHD published in the Journal of Clinical Oncology, and topline data reported from the pivotal AGAVE-201 trial of axatilimab in patients with chronic GVHD.
- A phase 1 study to evaluate SNDX-6352 in subjects with active cGVHD. ClinicalTrials.govidentifier: NCT03604692. https://clinicaltrials.gov/ct2/show/NCT03604692. Updated August 6, 2019. Accessed May 6, 2020.
- Data on file. Syndax Pharmaceuticals, Inc.
- Alexander K et al. CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. Journal of Clinical Investigation. October 2014. 10.1172/JC195935. 4367-4280.
- MacDonald, KP, et al. HSCT – Hematopoietic stem cell transplantation. Blood. 2017;5(129):13-21.