Axatilimab-csfr

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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