Inotek Pharmaceuticals is targeting the TM by mimicking the adenosine-mediated control of IOP seen in the healthy eye. Trabodenoson is a selective adenosine A1 receptor agonist that increases the expression, secretion, and activation of several matrix metalloproteinases (MMPs). These MMPs remodel the extracellular matrix of the TM and restore its mechanosensitivity to increase aqueous outflow and lower IOP.
The is active, said Cadmus C. Rich, MD, MBA, vice president of medical affairs and clinical development. But trabodenoson failed the primary endpoint the first phase III trial in ocular hypertension and primary open-angle glaucoma, MATrX-1.
“There were several secondary endpoints that were met,” Rich said. “The higher 6% dose in the trial had a statistically significant difference from placebo if you look across the average of all time points.”
Phase III results for trabodenoson were nearly identical with phase II results, he said, but the phase III trial showed significant clinical activity in the placebo group that was not seen in phase II. Early analysis suggest that the placebo group had a number of outliers and was not appropriately matched to the active group.
“Trabodenoson is clearly active and extremely well tolerated,” Rich said. “The data support once-daily dosing and we will be meeting with the FDA to discuss a path forward.”
A combination trial with latanoprost is expected to report topline results in mid-2017. Earlier data show strong IOP lowering for the combination and trabodenoson has a strong history in reperfusion injury, stroke, and myocardial infarction with a solid history of cytoprotection. Combination products account for about 75% of the glaucoma market, which makes trabodenoson/latanoprost a potentially rewarding combination.