References
Mohamad Mohty. (2024). CSF1R Blockade for Refractory Chronic Graft-versus-Host Disease. New England Journal of Medicine, 391(11), 1055–1059. https://doi.org/10.1056/nejme2407369
NiktimvoTM (axatilimab-csfr) is Now Available. (2025). Niktimvo.com. https://www.niktimvo.com/
NiktimvoTM (axatilimab-csfr) Prescribing Information. (2024). Niktimvo.com. https://www.niktimvo.com/niktimvo-prescribing-information
Incyte and Syndax Announce U.S. FDA Approval of NiktimvoTM (axatilimab-csfr) for the Treatment of Chronic Graft-Versus-Host Disease (GVHD) | Syndax Pharmaceuticals, Inc. (2024). Syndax Pharmaceuticals, Inc. https://ir.syndax.com/news-releases/news-release-details/incyte-and-syndax-announce-us-fda-approval-niktimvotm-axatilimab
gullapalli. (2024, September 13). NIKTIMVO for the Treatment of cGvHD, US. Clinical Trials Arena. https://www.clinicaltrialsarena.com/projects/niktimvo-axatilimab-for-treatment-of-cgvhd-us/
(2025). Clinicaltrials.gov. https://www.clinicaltrials.gov/study/NCT03604692
Wolff, D., Cutler, C., Lee, S. J., Iskra Pusic, Henrique Bittencourt, White, J., Hamadani, M., Arai, S., Amandeep Salhotra, Perez-Simon, J. A., Amin Alousi, Choe, H., Kwon, M., Arancha Bermúdez, Kim, I., Socié, G., Chhabra, S., Vedran Radojcic, O’Toole, T., & Tian, C. (2024). Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. New England Journal of Medicine, 391(11), 1002–1014. https://doi.org/10.1056/nejmoa2401537
Levien, T. L., & Baker, D. E. (2025). Axatilimab. Hospital Pharmacy. https://doi.org/10.1177/00185787241310874
T and B cell response is the primary
therapeutic target
Randomisation of AGAVE-201 was stratified based on the use of these drugs
Axatilimab-csfr
Pharmacokinetics
Elimination
Total clearance: 0.07L/h
Half-life
T 1/2: 10.7hrs - 108hrs
(0.15mg/kg - 3mg/kg)
Metabolism
Expected to be metabolised into small
peptides by catabolic pathways
Distribution
VD: 6.06L
Absorption
No systemic accumulation
observed
Administration
IV administration
0.3mg/kg (max 35mg/kg)
30 minutes Q2W
Pharmacodynamics
No known drug interactions or contraindications
Dose-dependent decrease in circulating
non-classical monocytes
Dose-dependent increase in CSF-1 and IL-34
Mechanism of action
Inhibits inflammation and fibrosis
Prevents macrophage activation
Subtopic
Blocks CSF-1 and IL-34 binding
Adverse Effects
Severe adverse effects
Infusion related bacterial or viral infection
Liver toxicity (increased AST and ALT)
Common side effects
Nausea
Fatigue
Headache
Muscle or joint pain
Pharamcoeconomics
Royalty Pharma and Syntax Pharmaceuticals partnership
$350 million in exchange for 13.8% royalties of US sales
IncyteCARES programe
Price per dose
50mg vial - $21,500
22mg vial - $11,500
9mg vial - $4,725
Future studies
Treatment of other diseases
Alternative route of administration
Ongoing phase III trials
Combination of Ataxilimab and corticosteroids
Use as 1st line treatment
Use in pregancy
No pre-clinical trials assessing reproductive
and developmental toxicity
Pregnant women excluded from AGAVE-201 trial
Considerations and caveats
Frequency and method of administration
Long term efficacy yet to be determined
Caters to steroid refractory patients
AGAVE-201 Trial
Primary end point was achieved in all groups
Highest ORR 74% and lowest toxicity
observed in 0.3mg group
Primary efficacy endpoint was objective response rate in first 6 cycles (24 weeks)
Secondary endpoint was proportion of patients reporting a clinically significant reduction in symptoms
241 participants
3mg/kg (Q4W)
1mg/kg (Q2W)
0.3mg/kg (Q2W)
Inclusion criteria
Recurrent or refractory active cGVHD despite 2 lines of systemic treatments
Active cGVHD requiring systemic
immune suppression
Allogenic HSCT recipients
> 2 years old (7-79)
Phase II, open-label, randomised,
multi centre trial
Regulatory Status
EMA
Estimated end date 31/12/2025
Phase II trial ongoing as of 26/02/2025
Same objectives as AGAVE-201 Trial
FDA
9mg and 22mg vial sizes
approved on 15/01/2025
50mg vial approved on 14/08/2024
Niktimvo
Treatment of chronic GVHD
Novel treatment approach
First drug of it's kind
Approved for use as a 3rd line
treatment for cGVHD
Approved for adults and children
weighing > 40kg
Humanised monoclonal antibody
MW: 150kDa
Produced in CHO cell lines
IgG4 monoclonal antibody
CSF-1 receptor antibody
Incyte and Syndax Pharmaceuticals
Current Treatments
2nd line treatment
Chemotherapeutics
Methotrexate
ROCK inhibitor
Belumosudil
TK inhibitor
Ibrutinib
Ruxolitinib
Monoclonal antibodies
Rituximab
Combined glucocorticoid and calcineurin inhibitors
1st line treatment
Glucocorticoids
50% success rate
Graft Versus Host Disease
Chronic GVHD
CSF-1 in cGVHD
M2 induced fibrosis
M1 induced inflammation
CSF-1R signalling promotes macrophage differentiation
Colony stimulating factor 1 binds to CSF-1R
Pathophysiology
Overactive B cell response characteristic of cGVHD
Type IV hypersensitivity reaction
Donor CD8 T-cell induced immune response
Skin tightness, swelling
Similar pathology to sclerosis
Dry persistent cough
Dry eyes and visual disturbances
Dry mouth, gum disease, mouth sores
Presents after 100 days post HSCT
40% - 70% of recipients
Acute GVHD
Treatment
Topical or systemic steroids
Symptoms
Jaundice
Nausea and vomiting
Diarrhoea
Rash
Presents within first 100 days post HSCT
35% - 50% of recipients
Complication of HSCT for various autoimmune diseases and cancers
