Nitish Mehta, MD
New York University
Yasha Modi, MD
Assistant Professor of Ophthalmology
New York University
Yesterday we reported on the favorable Phase II results from Genentech's BOULEVARD study
, where investigators randomized patients to ranibizumab or RG7716 for diabetic macular edema. RG7716 is Genentech’s bispecific molecule that suppresses both VEGF-A and Ang-2. This was presented at the 15th Angiognesis meeting
in Miami earlier this month. At the Angiogenesis meeting, Santen
also presented data for their new investigational molecule for neovascular AMD: DE-122.
Santen, a Japanese pharmaceutical, released interesting results from a Phase I/II study on the intravitreal use of DE-122
in refractory neovascular AMD. DE-122 is an ophthalmic formulation of the anti-endoglin antibody
, which was originally developed by TRACON Pharmaceuticals for use in various solid cancers.
Endoglin: The New Target
Endoglin has been shown to be expressed widely in the vasculature of neoplasms, increases in expression after anti-VEGF therapy, and has been implicated in resistance to anti-VEGF therapy
. In animal retinopathy models, anti-endoglin therapy has been shown to inhibit retinal neovascularization. Thus, it is suggested that targeting this pathway may be advantageous in patients with neovascular AMD.
Phase I/II Neovascular AMD Results
Santen reported no serious adverse events and a mean decrease in central retinal subfield thickness in a three-month, open-label, dose-escalation Phase I/II study of a single intravitreal injection of DE-122 at four dose levels in 12 subjects (n=3 per dose) with neovascular AMD refractory to VEGF inhibition.
Santen is escalating to a Phase 2A trial
evaluating a combination of DE-122 with ranibizumab compared to ranibizumab monotherapy for the treatment of neovascular AMD.
We look forward to further data in the near future. The bar is set quite high with anti-VEGF monotherapy, but we hope that incorporating other targets will further improve outcomes and decrease treatment burden for our patients.
Liu Y, et al
. Modulation of circulating protein biomarkers following TRC105 (anti-endoglin antibody) treatment in patients with advanced cancer. Cancer Med
2014 Jun; 3(3): 580–591.
Barnett JM, et al
. Endoglin Promotes Angiogenesis in Cell- and Animal-Based Models of Retinal Neovascularization. Invest Ophthalmol Vis Sci
2014 Oct; 55(10): 6490–6498.