Wouldn’t it be nice if patients with age-related macular degeneration (AMD) could receive their anti-VEGF agents topically, rather than by intravitreal injection? A cyclic retro-inverted peptidomimetic, D(Cys-Leu-Pro-Arg-Cys) – also known as Vasotide – is the latest candidate for that role. Vasotide works by selectively binding to the VEGF receptors VEGFR-1 and neuropilin-1 (NRP-1), and pilot studies performed in young mice with a retinopathy of prematurity-like phenotype showed that topical administration of the drug inhibited retinal angiogenesis (1). What’s now been published are the results of preclinical evaluations in three animal models: a mouse oxygen-induced retinopathy, vldr-null mice (a mouse model of retinal angiomatous proliferation), and laser-induced choroidal neovascularization in Old World monkeys (2). In the latter experiment, topically-formulated Vasotide was administered twice daily from day 1 through day 5 after laser photocoagulation, then once daily on days 6 through 21. On retinal assessment at day 29, Vasotide use was associated with a significant (p<0.0001) reduction in the development of grade III and IV lesions compared with monkeys treated with vehicle alone – an outcome comparable to those achieved by ranibizumab or bevacizumab in this model.
In addition to the obvious benefits of a topical route of administration, the researchers hope that the fact that Vasotide targets NRP-1 in addition to VEGF-A, the drug might offer an alternative to patients who respond poorly to current treatments. In terms of the future potential of the drug, first author, Richard Sidman said, “In addition to future clinical trials on AMD and ROP, we think that diabetic retinopathy and certain forms of cancer may also prove to be responsive to Vasotide.”
References
- RL Giordano et al., “From combinatorial peptide selection to drug prototype (I): targeting the vascular endothelial growth factor receptor pathway”, Proc Natl Acad Sci USA, 107, 5112–5117 (2010). PMID: 20190181. RL Sidman, et al., “The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease”, Sci Transl Med, 7, 309ra165 (2015). PMID: 26468327.
