Recently released topline results from a phase Iib clinical trial of treatment for neovascular age-related macular degeneration show significantly greater improvement in visual acuity among patients receiving combination therapy with Fovista, an investigational aptamer directed against PDGF-B, plus anti-VEGF therapy compared with anti-VEGF therapy alone.
Princeton, NJ-Recently released topline results from a phase IIb clinical trial of treatment for neovascular age-related macular degeneration (AMD) show significantly greater improvement in visual acuity among patients receiving combination therapy with Fovista (formerly E10030, Ophthotech), an investigational aptamer directed against platelet-derived growth factor subunit B (PDGF-B), plus anti-vascular endothelial growth factor (VEGF) therapy compared with anti-VEGF therapy alone.
Mean change in ETDRS visual acuity from baseline to week 24 was assessed as the primary efficacy endpoint. The results showed a dose-response benefit for Fovista and statistically significant superiority (p = 0.019) comparing the combination of Fovista 1.5 mg and ranibizumab versus sham plus ranibizumab. Mean gain in ETDRS visual acuity was 10.6 letters for patients treated with the higher dose of Fovista in combination with ranibizumab and 6.5 letters for controls receiving ranibizumab monotherapy.
"Anti-PDGF therapy with Fovista addresses the pathology through another mechanism that allows regression of the neovascular membrane and a greater functional benefit," he added. "The 62% greater gain in visual acuity achieved with the combination is astonishing and something we would have previously thought was unattainable."
"Anti-PDGF therapy with Fovista attacks a different target [from] anti-VEGF therapy in treating exudative AMD," Dr. D'Amico said. "Importantly, Fovista is not just a longer-acting anti-VEGF agent or one that is used in a different route of administration, but it delivers a unique mechanism that appears to be complementary with anti-VEGF therapy.
"Fovista added to ranibizumab is like having a gasoline additive that substantially extends fuel economy without any evidence of deleterious effects," he said. "The results achieved with the combination are beyond what we would have expected to achieve in an initial efficacy trial, and if they can be sustained in the definitive phase III trials, we will see a new treatment paradigm for exudative AMD."
Dr. Dugel is also encouraged by the lack of any safety signals found with the combination regimen.
"Although this is just a phase IIb study, it is extraordinary in that it is the largest phase II study ever conducted in retina and perhaps in all of ophthalmology," he said. "Having data from a trial enrolling more than 440 patients builds confidence in the study results."
Samir Patel, MD, co-founder, chief executive officer, and president of Ophthotech, said, "We believe the statistical strength and clinical significance of this trial is great news for patients. Given the exciting news from this trial, Ophthotech will devote all its resources to bring Fovista (1.5 mg anti-PDGF) to market."