Clinicians are less than a year into the era of rho-kinase (ROCK) inhibitor use for glaucoma—Aerie’s Rhopressa launched in the US last April—but researchers are already hard at work on additions to this nascent drug class. A recent preclinical study demonstrated the significant IOP-lowering ability of ITRI-E-212 in an ocular hypertensive and normotensive rabbit model. In vitro biochemical assays revealed the ROCK inhibitor was highly effective at inhibiting ROCK2 compared with other compounds.

Researchers wanted to create a new amino-isoquinoline ROCK inhibitor compound that would have excellent IOP-lowering effects and corneal penetration, be easily manufactured and cause less conjunctival hyperemia. The most effective compound for lowering IOP was ITRI-E-212, which demonstrated superior inhibitory activity and high relative selectivity for ROCK2. 

After administration of 1% ITRI-E-212 eye drops, a maximum IOP reduction of 28.4% was attained at six hours in the ocular hypertensive model; in the normotensive model, a maximum IOP reduction of 25.3% was attained at four hours. The significant difference in IOP reduction was not observed until six hours after the administration of 1% ITRI-E-212 in the normotensive and hypertensive groups. Researchers observed only transient, mild hyperemia.

The study concluded that ITRI-E-212 is a novel selective ROCK inhibitor that may be a promising new pharmacologic agent for hindering the progression of glaucoma. 

Hsu CR, Chen YH, Liu CP, et al. A highly selective rho-kinase inhibitor (ITRI-E-212) potentially treats glaucoma upon topical administration with low incidence of ocular hyperemia. Invest Ophthalmol Vis Sci. 2019;60(2):624-33.