Pharmacological characterization and safety of the Nintedanib IVT^XR ocular implant

Abstract

Purpose : Treatments targeting vascular endothelial growth factor-A (anti–VEGF-As) are an established standard of care for neovascular age-related macular degeneration (nAMD), but there remains high unmet need for new treatment options. Nintedanib is a tyrosine kinase inhibitor that simultaneously blocks the signaling of several receptors implicated in the pathology of nAMD, including VEGF receptor 2, fibroblast growth factor receptors 1–3, and platelet-derived growth factor receptors α and β. The pharmacokinetics of orally administered nintedanib are well known; this series of preclinical studies examined a new extended-release ocular implant (Nintedanib IVT^XR).

Methods : Nintedanib IVT^XR is an intravitreally delivered ocular implant that releases nintedanib. One 4-week toxicity study in rabbits and one 13-week toxicology study in minipigs were conducted. In both studies, there were two dose groups: high (two implants/eye) and low (one implant/eye). Endpoints included ophthalmological investigations, optical coherence tomography (OCT) images, electroretinograms (ERGs), toxicokinetics (TK), and extended histopathology of the eyes. Local exposure of the vitreous, retina, lens, and all other localizations was measured.

Results : Prior in vitro investigations showed that the implant provides sustained release over approximately 3 months. There were no pertinent, drug- or treatment-related findings in the 4-week or the 13-week study. There were also no ocular changes noted through OCT, ERGs, or histopathology. TK analyses showed substantial local exposure of the eyes, including the retina.

Conclusions : Following these promising toxicology findings, Nintedanib IVT^XR will be investigated in humans.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.