Name: AXPAXLI (axitinib intravitreal implant) in Neovascular age-related macular degeneration: Mechanism of action
Published: 2026-09-17T18:54:38-04:00

Intracellular VEGF receptor tyrosine kinase inhibition

“TKIs bind the intracellular tyrosine kinase domains of VEGF receptors, inhibiting ATP binding and preventing activation of pro-angiogenic signaling” (opens the source at this quote in a new tab)

Receptor targets of axitinib: review

“Axitinib is a second-generation TKI that potently targets the VEGFR1, VEGFR2, and VEGFR3 tyrosine kinase receptors.” (opens the source at this quote in a new tab)
“It also inhibits the PDGFR α and PDGFR β tyrosine kinases and c-Kit receptors at higher concentrations.” (opens the source at this quote in a new tab)

Class context: mechanism of action in the oral axitinib (INLYTA) label

“Axitinib has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations.” (opens the source at this quote in a new tab)

Contrast with extracellular anti-VEGF ligand binding

“Anti-VEGFs act on the extracellular side by binding selective ligands, like VEGF-A, to prevent receptor binding and pro-angiogenic activity” (opens the source at this quote in a new tab)

Hydrogel drug-release mechanism

“Cross-linked multi-arm PEG hydrogel network with hydrolyzable ester linkages” (opens the source at this quote in a new tab)
“Micronized axitinib entrapped in hydrogel steadily dissolves into vitreous, then diffuses into ocular tissues” (opens the source at this quote in a new tab)
“Hydrogel degrades via hydrolysis (like dissolvable sutures), implant bioresorbs, and remaining axitinib is released for continued delivery” (opens the source at this quote in a new tab)

ELUTYX hydrogel platform chemistry

“We create our hydrogels by cross-linking PEG molecules to form a network that resembles a three-dimensional mesh on a molecular level.” (opens the source at this quote in a new tab)
“We design these hydrogels to slowly degrade in the presence of water, a process called hydrolysis, by inserting a biodegradable linkage between the PEG molecule and the cross-linked molecule.” (opens the source at this quote in a new tab)

Rationale for sustained delivery of a tyrosine kinase inhibitor

“In the absence of a sophisticated drug delivery system, TKIs have been difficult to deliver to the eye for acceptable time frames at therapeutic levels without causing local and systemic toxicity due to low drug solubility, very short half-lives in solution, and off-target effects.” (opens the source at this quote in a new tab)

Combined VEGF and PDGF pathway inhibition: in vitro and rat choroidal neovascularization models

“Axitinib inhibited neovascularization better than anti-VEGF and/or anti-hPDGF-B mAb in the in vitro models demonstrating that combined inhibition of both VEGF and PDGF pathways may be synergistic in treating wet-AMD.” (opens the source at this quote in a new tab)