Allergan has halted development of its siRNA-based wet age-related macular degeneration, Sirna-027 is the first chemically modified short interfering RNA (siRNA) targeting Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1).

VEGFR-1 is found primarily on vascular endothelial cells and is stimulated by both VEGF and placental growth factor (PlGF), resulting in the growth of new blood vessels⁽¹¹⁾.

By targeting VEGFR-1, Sirna-027 is designed to reduce pathologic angiogenesis mediated by both VEGF and PlGF.

Development was halted for AGN-745 after the drug failed to meet a key efficacy endpoint in a phase II study.

The trial compared the effect of three different monthly doses of AGN-745 with Genentech’s antibody drug Lucentis^®, the standard of care for AMD, in treating the subfoveal choroidal neovascularization associated with the disease.

Both drugs were administered via intravitreal injection⁽¹²⁾.

Apparently no safety issues were associated with AGN-745, a chemically modified siRNA.

But since the drug did “not meet its efficacy hurdle” — improvement in visual acuity — Allergan opted to halt its development⁽¹³⁾.