Abstract
Purpose :
Tie2 dysfunction in the conventional outflow pathway has been implicated in glaucoma (Kim et al, JCI 2017; 127:3877-96). AKB-9778 is a small molecule inhibitor of VE-PTP, a critical negative regulator of Tie2, that is in clinical development for the treatment of diabetic retinopathy. The purpose of this exploratory analysis was to assess the effect of subcutaneous (SC) administration of AKB-9778, compared to placebo, on intraocular pressure (IOP) in patients with diabetic retinopathy.
Methods :
Tie2 dysfunction in the conventional outflow pathway has been implicated in glaucoma (Kim et al, JCI 2017; 127:3877-96). AKB-9778 is a small molecule inhibitor of VE-PTP, a critical negative regulator of Tie2, that is in clinical development for the treatment of diabetic retinopathy. The purpose of this exploratory analysis was to assess the effect of subcutaneous (SC) administration of AKB-9778, compared to placebo, on intraocular pressure (IOP) in patients with diabetic retinopathy.
Results :
Pretreatment baseline IOP assessment showed both the study eye and fellow eye of each treatment group to be normotensive and well balanced between treatment groups (Table 1). Both active AKB-9778 treatment arms achieved statistically significant reductions in IOP in both the study eye and the fellow eye compared to baseline, whereas there was no change in IOP in the placebo arm. In the subgroup of patients with baseline IOP > 16 mmHg, a greater IOP reduction was achieved.
Conclusions :
SC administration of the Tie2 activator AKB-9778 was well tolerated and led to a statistically significant IOP reduction from baseline that was also statistically significantly greater than placebo. These results are consistent with preclinical and genetic evidence for the importance of Tie2 function on the conventional outflow pathway. These findings support evaluation of Tie2 activation by AKB-9778 as a potential approach for IOP reduction in patients with open angle glaucoma or ocular hypertension.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.