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    This randomized, controlled trial validates platelet-derived growth factor (PDGF) as an important target for wet AMD, and may represent the beginning of a new era of combination therapy.

    It was a phase 2b pharmacologic superiority study that assessed the efficacy of a combination of an anti-PDGF (Fovista, Ophthotech) and ranibizumab compared with ranibizumab alone. Subjects included 449 treatment-naïve patients with subfoveal wet AMD randomized to 2 different doses of combination therapy or monotherapy.

    At 24 weeks, the high-dose combination group achieved significantly better vision (10.5 vs. 6.5 letters, P=0.019), representing a 62% additional benefit.

    The benefit of combination therapy was consistent across all subgroups, regardless of baseline VA, lesion size or central subfield thickness on OCT. All clinically relevant treatment end points of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the combination group.  No significant safety issues were observed in any treatment group.

    Previous studies have shown that pericytes play an important role in the limitations of anti-VEGF therapy. Pericytes share a common basement membrane with endothelial cells, intimately coating them. Pericytes provide endothelial cells with VEGF and other growth and cell survival factors by paracrine and/or juxtacrine signaling mechanisms. Consequently, the neovascular endothelial cells are protected in the setting of anti-VEGF therapy.

    In a preclinical model, the anti-PDGF stripped neovascular pericytes from the underlying endothelial cells, leaving the underlying endothelial cells in an unprotected and vulnerable state, thereby increasing their sensitivity to the effects of VEGF blockade.

    Based on the results the phase 2b study, Ophthotech reported that it plans to expedite the preparation of a phase 3 registration program with the goal of bringing anti-PDGF therapy to patients with wet AMD as soon as possible.