Study of Anti-PDGF and Anti-VEGF therapy shows significant neovascular regression and enhanced visual outcome

Ophthotech Corp. has announced positive results of a phase I clinical study evaluating E10030, its novel anti-platelet derived growth factor (anti-PDGF) in conjunction with an anti-vascular endothelial growth factor (anti-VEGF), to treat wet age-related macular degeneration (wet AMD). Anti-PDGF therapy resulted in enhanced visual outcome and was associated with significant neovascular regression. The results were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2009 Annual Meeting in Fort Lauderdale.

Fifty nine percent of patients treated with anti-PDGF and anti-VEGF gained significant vision (3-line gain) at week 12 after therapy. One hundred percent of treated patients demonstrated neovascular regression. E10030 was well tolerated with no evidence of drug-related adverse events. Current standard of care treatment utilizing monotherapy anti-VEGF results in 3-line visual gain in approximately one third of patients and without significant neovascular regression.

“Marked neovascular regression, a first in any study, with an outstanding level of visual gain, is very promising for our patients. My clinical experience with current monotherapy anti-VEGF regimen in wet AMD is consistent with published studies, which show that on average neovascular regression does not occur,” said Dr. Lawrence J. Singerman, Clinical Professor at Case Western Reserve University and a principal investigator in over 50 macular clinical trials.

E10030 is an aptamer targeting PDGF, a key molecule involved in the recruitment and maturation of pericytes. Pericytes in neovascular tissue have been shown to be protective and play a major role in anti-VEGF treatment resistance. E10030 strips the pericytes from the neovascular tissue rendering it highly sensitive to an anti-VEGF attack.

“The objective and robust response of neovascular regression is consistent with the biologic activity of E10030. I look forward to a randomized trial design to confirm the strong proof of concept data of this study,” said Dr. Donald J. D'Amico, professor and chairman, department of Ophthalmology, Weill Cornell Medical College, New York-Presbyterian Hospital.

“It is exciting to see our clinical trial confirm the strong preclinical data from oncology and ophthalmic studies targeting the molecules regulating pericyte and endothelial cell survival. Ophthotech will continue to devote its resources towards an accelerated development of our anti-PDGF compound,” said Dr Samir C. Patel, president and CEO of Ophthotech Corp.

E10030 is one of three compounds that Ophthotech is developing to treat wet and dry AMD. Additional molecular entities include an anti-C5 aptamer and volociximab, an anti-angiogenic monoclonal antibody targeting the a5B1 integrin, both currently in a Phase I study.