September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The Tie2 Activator AKB-9778, Used In Combination With Ranibizumab, Enhances Reduction Of Diabetic Macular Edema Compared To Ranibizumab Monotherapy
Author Affiliations & Notes
  • Arshad Khanani
    Ophthalmology, Sierra Eye Associates, Reno, Nevada, United States
  • Footnotes
    Commercial Relationships   Arshad Khanani, Aerpio Therapeutics (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Arshad Khanani; The Tie2 Activator AKB-9778, Used In Combination With Ranibizumab, Enhances Reduction Of Diabetic Macular Edema Compared To Ranibizumab Monotherapy. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To assess the effect of subcutaneous injections (sc) of 15 mg of AKB-9778 BID either as monotherapy (MT) or as combination therapy with ranibizumab (RBZ) on macular edema in subjects with DME.

Methods : This was a phase 2A, randomized, double-masked, double-dummy trial. 144 patients with DME and central subfield thickness (CST) ≥ 325 µm measured by SD-OCT were enrolled at 36 US sites. Patients were randomized to receive: 1. AKB-9778 MT (sc AKB-9778 15 mg BID + monthly sham IVT injection); 2. AKB-9778+RBZ (sc AKB-9778 15mg BID + monthly IVT injection of 0.3 mg RBZ); or 3. RBZ MT (sc placebo injection BID + monthly IVT injection of 0.3 mg RBZ). The treatment period was 3 months followed by 2 months of observation. The main outcome measure was change from baseline in CST (by ANCOVA with baseline CST as covariate). Other assessments included BCVA, clinical eye examination, 7-field fundus photographs, fluorescein angiogram, physical examination, vital signs, safety laboratory tests, PK assessments, and adverse event reporting.

Results : The mean change from baseline CST at end of treatment was 6.2±88.4 µm in the AKB-9778 MT group, -109.2±17.2 µm in the RBZ MT group, and -163.8±24.3 µm in the AKB-9778+RBZ group (p=0.008 compared to RBZ MT). Mean CST at month 3 was 339.9±11.2 µm with 29.2% of eyes ≤ 300 µm in the AKB-9778+RBZ group versus 391.2±17.2 µm with 17.0% of eyes ≤ 300 µm in the RBZ MT group. The mean change from baseline BCVA was 1.5±1.2 letters in the AKB-9778 MT group, 5.7±1.2 letters in the RBZ MT group, and 6.3±1.3 letters in the AKB-9778+RBZ group. The percentage of eyes that gained ≥10 letters was 8.7% in the AKB-9778 MT group, 29.8% in the RBZ MT group, and 35.4% in the AKB-9778+RBZ group. In the RBZ MT group, 4.2% of qualified fellow eyes showed ≥2-step reduction in diabetic retinopathy severity score, compared to 11.4% of such eyes in the AKB-9778 groups.
AKB-9778 was well tolerated, with no treatment group differences in serious AEs, severe AEs, or in clinically significant abnormalities in physical examination, ophthalmology examination or laboratory tests.

Conclusions : These results demonstrate that Tie2 activation by subcutaneously administered AKB-9778 in combination with anti-VEGF therapy enhances the effect of anti-VEGF therapy on diabetic macular edema.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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