Abstract: SA-PO150
Tie2 Activation via VE-PTP Inhibition for Treatment of Diabetic Kidney Disease
Session Information
- Diabetic Kidney Disease: Clinical - II
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Peters, Kevin G., Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
- Brigell, Mitchell, Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
- Pakola, Steve, Aerpio Pharmaceuticals, Cincinnati, Ohio, United States
Background
Considering the current epidemic of diabetes, new treatments for diabetic vascular complications, including diabetic kidney disease (DKD) are urgently needed. VE-PTP is a vascular endothelial receptor tyrosine phosphatase that negatively regulates Tie2 activation, a critical axis for maintaining endothelial function and vascular stability. Importantly, VE-PTP is upregulated by hyperglycemia and hypoxia, conditions associated with decreased Tie2 activation and progression of diabetic complications. Thus, targeting VE-PTP inhibition to restore Tie2 activation is a promising approach to treat diabetic vascular complications, including DKD. Here we report results from a post-hoc analysis demonstrating improvement in UACR in patients with diabetic eye disease treated for three months with AKB-9778, a potent and selective small molecule VE-PTP inhibitor.
Methods
The TIME-2 study was a Phase 2a, double-masked, parallel-group trial in which 144 patients with diabetic retinopathy complicated by diabetic macular edema were randomized to one of three treatment groups: AKB-9778 (15 mg) subcutaneous (SC) BID monotherapy plus sham intravitreal injection; AKB-9778 SC BID plus monthly Lucentis (0.3mg) intravitreal injection; and placebo SC BID plus monthly Lucentis intravitreal injection monotherapy. Although the study was designed to assess the effect of AKB-9778 on diabetic eye disease, UACR was measured at baseline and at end of the 3-month treatment period. Patients with increased UACR at baseline (UACR ≥30 mg/g) were included in the analysis.
Results
About 50% of patients in the study had UACR ≥30 mg/g at baseline, approximately equally distributed among the three treatment groups. There was an ~ 20% reduction in geometric mean UACR from baseline in both AKB-9778 active treatment arms, while there was an increase in UACR in the placebo arm (Figure 1).
Conclusion
These findings represent the first clinical evidence of potential beneficial effects of a VE-PTP inhibitor in patients with DKD and underscore the therapeutic potential of Tie2 activation in DKD and other diabetic vascular complications.
Funding
- Commercial Support – Aerpio Pharmaceuticals, Inc.