On August 14, 2024, the U.S. Food and Drug Administration (FDA) approved a colony stimulating factor-1 receptor (CSF-1R)-blocking antibody, NIKTIMVO (axatilimab-csfr) developed by Incyte Corporation (and in-licensed from Syndax Pharmaceuticals), for treatment of chronic graft-versus-host disease (cGvHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg.[1]
Patients that receive stem cell transplantation from a donor (allogeneic stem cell transplant), may develop cGvHD when the transplanted cells initiate an immune response against the patient’s organs.[2] cGvHD is the leading cause of long-term morbidity and mortality after allogeneic stem cell transplant. [3] The pathophysiology of cGvHD is complex and various immune cell types, including macrophages, have been implicated in mediating the immune dysregulation.[4] A number of first-line and second-line therapies for cGvHD, including monoclonal antibodies, have been developed, and new therapies targeting different signaling pathways in the different immune cells continue to be developed.[5]
NIKTIMVO is a monoclonal antibody that binds to CSF-1R expressed on monocytes and macrophages.[6] Preclinical studies in models of cGvHD showed tissue accumulation of monocytes and macrophages that depend on CSF-1R signaling, and effectiveness of anti-CSF-1R monoclonal antibody treatment.[7]
Efficacy of NIKTIMVO was evaluated in a randomized, open-label, multicenter study (AGAVE-201) in adult and pediatric patients with recurrent or refractory cGvHD who had received at least 2 lines of systemic therapy and required additional treatment.[8] NIKTIMVO achieved an overall response rate of 75% in 79 patients, with a median time to response of 1.5 months and a median duration of response of 1.9 months.[9] Serious adverse events were observed in 44% of patients, with infection (57% of patients) being the most commonly occurring adverse reactions.[10]
NIKTIMVO is the second FDA-approved treatment for Incyte, following approval of JAKAFI (ruxolitinib) in 2021, which is a small molecule inhibitor of an intracellular signaling in T cells, was approve as a second or third line systemic therapy.[11] Incyte reported net product revenue from JAKAFI of $636 million in the third quarter of 2023, and projected net product revenue of $2.59 – $2.62 billion for 2023.[12]
Editor: Brenden S. Gingrich, Ph.D.
[1] NIKTIMVOTM (axatilimab-csfr) Label at 1 (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axatilimab-csfr-chronic-graft-versus-host-disease)
[2] Syndax Press Release, August 14, 2024 (https://ir.syndax.com/news-releases/news-release-details/incyte-and-syndax-announce-us-fda-approval-niktimvotm-axatilimab)
[3] Buxbaum et al. Chronic GvHD NIH Consensus Project Biology Task Force: evolving path to personalized treatment of chronic GvHD. Blood Adv 2023; 7 (17): 4886–4902 at 4886.
[4] Buxbaum et al. at 4887
[5] Buxbaum et al.
[6] NIKTIMVOTM Label at 10.
[7] Buxbaum et al. at 4890
[8] NIKTIMVOTM Label at 12-14
[9] Id.
[10] NIKTIVMOTM Label at 5-6
[11] https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ruxolitinib-chronic-graft-versus-host-disease
[12] Incyte Press Release, October 31, 2023
