MOA
Axatilimab targets this on the of surface cells
What is CSF-1R
This is the number of lines of therapy patients had to be refractory to for AGAVE201
what is two prior lines of systemic therapy
This is the recommended approved dose regimen for Niktimvo?
What is 0.3mg/kg Q2W IV, until disease progression, or unacceptable toxicity
These are the warnings and precautions in the PI
What are 1. Infusion-Related Reactions: Interrupt or slow the rate of infusion or permanently discontinue NIKTIMVO based on severity of reaction; and 2. Embryo-Fetal Toxicity: May cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception
This was the median duration of treatment of Axatilimab in the 0.3mg/kg cohort and the percentage of patients treated for more than 6 months
What is 10.3 months (range: 0.5 to 28.6 months), and 73.4%
CSF-1R is predominately expressed on these innate, myeloid immune cells
What are monocytes and macrophages
These were the only allowed medications (in addition to Axa) that patients could be on when randomized to AGAVE201
What is treatment with GVHD prophylaxis and standard care systemic cGVHD therapies were permitted as long as the patient had been on a stable dose for at least 2 weeks prior to study.
This is the final concentration that Axatilimab should be prepared at for infusion
What is a final concentration between the range of 0.24 mg/mL and 0.75 mg/mL
These are the percentages of discontinuations and dose reductions specific to AR's
What are permanent discontinuation of NIKTIMVO due to an adverse reaction occurred in 10% of patients and dose reduction due to adverse reaction occurred in 8% of patients
This was the ORR and mTTR for pts treated with 0.3mg/kg on AGAVE201
What are 75% and 1.5 months
These are the monocytes predominately reduced in circulation of Axatilimab treated patients
What are non-classical monocytes
This was the percentage of patients previously treated with Ruxolitinib, Belumosudil and Ibrutinib in the 0.3mg/kg cohort on AGAVE201
What are 72% (Rux), 34% (Ibr), 20%(Bel)
These are the two methods for which axatilimab may be stored
What are 1. at room temperature [up to 25°C (77°F)] for no more than 4 hours from the time of preparation to the end of the infusion; and 2. Refrigerated at 2°C to 8°C (36°F to 46°F) for no more than 24 hours. If refrigerated, allow the diluted solution to come to room temperature prior to administration. The diluted solution must be administered within 4 hours (including infusion time) once it is removed from the refrigerator
This is the proposed mechanism for ALT and AST lab chemistry increases in patients treated with Axatilimab
What is Liver-resident macrophages, Kupffer cells, express CSF-1R and are impacted by CSF-1R inhibition, leading to decreased enzyme clearance and increased levels of LFTs. Axatilimab may induce dose-dependent and reversible increases in circulating levels of ALT and AST
This is the definition for DOR resulting in mDOR of 1.9months
What is the median duration of response, calculated from first response to progression, death, or new systemic therapies for cGVHD
This profibrotic cytokine, secreted from M2/pro fibrotic macrophages, has been shown to be depleted in circulation of Axatilimab treated patients
What is TGF-B
This was the median lines of prior therapy, median time from diagnosis and median global GVHD severity scores for patients randomized to the 0.3mg/kg on AGAVE201
What are 4 (PLOT); 47 (months) and 7 (score)
This is the guidance for premedication in the PI
What is Premedicate with an antihistamine and an antipyretic for patients who have previously experienced an infusion-related reaction to NIKTIMVO
These correlated with drug hypersensitivity but, importantly NOT efficacy of Axatilimab and their presence was detected in this number of patients
What are neutralizing anti-drug antibodies (Nab) and NAb were detected in 47 of 93 cGVHD patients with treatment-emergent ADAs.
This was the mFFS for the 0.3mg/kg group (reported at ASTCT 2024)
What is 17.3months
This is the MOA statement from the Axatilmab PI
Blocking CSF-1R with axatilimab-csf reduces the levels of these circulating proinflammatory and profibrotic monocytes and monocyte-derived macrophages, as demonstrated by a reduction of nonclassical monocyte counts in nonclinical studies with axatilimab-csfr, and inhibits the activity of pathogenic macrophages in tissues.
These patients were excluded from RockStar but not AGAVE201
Who are patients with >5 PLOTs; patients with grade 3 lung or <FEV 39% at baseline; patients treated with certain active cGVHD therapies (i.e. ECP); patients not on steroids (optional for AGAVE201)
This is the dose modification guidance for elevated CPK, amylase or lipase
What is if >/= Gr3: If diagnostic evaluation results show no evidence of end-organ damage, continue NIKTIMVO without dose reduction. If diagnostic evaluation results show evidence of end-organ damage, permanently discontinue NIKTIMVO. If symptomatic >/= Gr3, Permanently discontinue NIKTIMVO.
These are the clinically relevant adverse reactions in < 10% of patients who received NIKTIMVO
What are Eye disorders: periorbital edema; Skin and subcutaneous skin disorders: pruritus; Vascular disorders: hypertension
These are proposed hypotheses for the 0.3mg/kg dose being the chosen approved dose for axatilimab
What is the 0.3mg/kg dose demonstrated the best safety to efficacy benefit for these proposed reasons (we don't really know!): 1. Less toxicity/dose modification leading to longer but quantitatively less exposure; 2. Pharmacodynamic impacts of less prolonged suppression of monocytes and increased levels of ligands