tivozanib ocular form / LG Chem, Astellas - LARVOL DELTA

Preclinical Ocular Pharmacokinetics and Efficacy of Novel Tivozanib Eye Drops for Neovascular Age-Related Macular Degeneration. (PubMed, Invest Ophthalmol Vis Sci) - "In the monkey CNV model, nTivo eye drops significantly reduced the neovascularization lesion area. The nTivo eye drop formulation may be a potential new treatment option for nAMD due to its preferable ocular pharmacokinetic and anti-angiogenic profiles based on potential contributions of nanocrystallization and the melanin binding properties of tivozanib."

Journal • PK/PD data • Preclinical • Age-related Macular Degeneration • Macular Degeneration • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

Ocular pharmacokinetics of tivozanib eye drops in patients with neovascular age-related macular degeneration: comparison with phase 1 trials of oral tivozanib in solid tumors. (PubMed, Int J Retina Vitreous) - "Given the integrated analysis, we hypothesize that tivozanib eye drops could predominantly be delivered to the posterior eye segment through the ocular tissues, with limited contribution by the systemic drug delivery pathway. This hypothesis provides meaningful insights into the ocular pharmacokinetics of tivozanib eye drops."

Journal • P1 data • PK/PD data • Age-related Macular Degeneration • Cardiovascular • Genito-urinary Cancer • Hypertension • Macular Degeneration • Oncology • Ophthalmology • Retinal Disorders • Solid Tumor • Wet Age-related Macular Degeneration

Receptor tyrosine kinase inhibitor tivozanib regulates cell state plasticity and restores MITF dependency in BRAF wild-type melanoma. (PubMed, Acta Pharmacol Sin) - "Mechanistically, tivozanib induced cell state transition from MITFlow to MITFhigh state via VEGFR2 inhibition followed by NF-κB pathway activation, restoring MITF transcriptional activity and growth dependency. The combination of tivozanib and TT-012 synergistically inhibited melanoma growth both in vitro and in vivo, underscoring its potential as a novel therapeutic strategy for BRAFWT melanoma."

Journal • Melanoma • Oncology • Ophthalmology • Solid Tumor • BRAF • MITF

Pre-clinical ocular pharmacokinetics and efficacy of a novel Tivozanib eye drop for neovascular age-related macular degeneration (ARVO 2024) - "Our in vivo data suggest that nTivo eye drops could be a potential therapeutic agent for treating posterior eye diseases. The accumulation and sustained exposure to tivozanib in the choroid and retina, which may contribute to the efficacy in retinal vascular disease, may have resulted from its innate melanin-binding properties and nano-crystallized formulation of tivozanib."

PK/PD data • Preclinical • Age-related Macular Degeneration • Macular Degeneration • Macular Edema • Ophthalmology • Retinal Disorders • Wet Age-related Macular Degeneration

VEGF receptor 2 inhibitor nintedanib completely reverts VEGF-A-induced disturbances of barriers formed by retinal endothelial cells or long-term cultivated ARPE-19 cells. (PubMed, Exp Eye Res) - "Blocking mainly VEGFR2 with 10 nM nintedanib, 10 nM tivozanib or 500 nM ZM323881 efficiently reverted these changes within one day; higher concentrations of nintedanib or additional inhibition of neuropilin-1 were not superior. Taken together, inhibition of VEGFR2 efficiently reverts VEGF-A-induced barrier disturbances of both cell types forming and regulating the inner and outer blood-retina barrier. As synergistic actions of growth factors seem to play only a minor role in inducing a barrier dysfunction, specific inhibition of VEGFR2 could be an interesting option to treat VEGF-A-induced macular edema without obvious effects on vitality and functions of REC and RPE cells."

Journal • CLDN1 • KDR • NRP1