title: Dual Antagonism of PDGF and VEGF in Neovascular Age-Related Macular Degeneration: A Phase IIb, Multicenter, Randomized Controlled Trial.
abstract: To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, administered in combination with the anti-vascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD).
  
  
  
  Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial.
  
  
  
  Four hundred forty-nine patients with treatment-naïve nAMD.
  
  
  
  Participants were randomized in a 1:1:1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks.
  
  
  
  The prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks.
  
  
  
  No significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. 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 E10030 1.5 mg combination group.
  
  
  
  In this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial.
authors.affiliation: Department of Ophthalmology, Duke Reading Center, Duke University, Durham, North Carolina. Electronic address: jaffe001@mc.duke.edu.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Jaffe
authors.affiliation: Ophthotech Corporation, New York, NY.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Ciulla
authors.affiliation: Azienda Ospedaliero-Universitaria di Bologna-Policlinico S. Orsola-Malpighi, Unità Operativa Oftalmologia-Ciardella, Bologna, Italy.
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Ciardella
authors.affiliation: Centre Paradis Monticelli, Marseilles, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Devin
authors.affiliation: Retinal Consultants of Arizona, Phoenix, Arizona, and USC Roski Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California.
authors.forename: Pravin U
authors.initials: PU
authors.lastname: Dugel
authors.affiliation: Department of Surgical Science, Eye Clinic, University of Torino, Torino, Italy.
authors.forename: Chiara M
authors.initials: CM
authors.lastname: Eandi
authors.affiliation: Ophthotech Corporation, New York, NY.
authors.forename: Harvey
authors.initials: H
authors.lastname: Masonson
authors.affiliation: Institut de la Macula, Centro Medico Teknon, QuironSalud, and Barcelona Macula Foundation, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Monés
authors.affiliation: Retinal Consultants, Sacramento, California.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Pearlman
authors.affiliation: Centre Rabelais, Lyon, France.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Quaranta-El Maftouhi
authors.affiliation: Università Tor Vergata-Fondazione PTV Policlinico Tor Vergata, Unità Operativa Semplice Dipartimentale Patologie Retiniche-Dipartimento di Chirurgia, Rome, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Ophthotech Corporation, New York, NY.
authors.forename: Keith
authors.initials: K
authors.lastname: Westby
authors.affiliation: Ophthotech Corporation, New York, NY.
authors.forename: Samir C
authors.initials: SC
authors.lastname: Patel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D052157:Aptamers, Nucleotide / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D000069579:Ranibizumab / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D052157:Aptamers, Nucleotide; C000621266:E10030 aptamer; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab