Pegaptanib 1-year systemic safety results from a safety-pharmacokinetic trial in patients with neovascular age-related macular degeneration

Ophthalmology. 2007 Sep;114(9):1702-12. doi: 10.1016/j.ophtha.2007.02.021. Epub 2007 May 23.


Objective: To characterize the safety, tolerability, and pharmacokinetics of the pegylated anti-vascular endothelial growth factor (VEGF) aptamer pegaptanib sodium in subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD).

Design: Prospective 2-cohort study: (1) open-label cohort and (2) randomized, double-masked, uncontrolled multicenter trial.

Participants: In the combined cohorts, 147 subjects with any angiographic subtype of subfoveal choroidal neovascularization secondary to AMD and best-corrected visual acuities (VAs) in the study eye of 20/40 to 20/320 and in the fellow eye of 20/800 or better received pegaptanib sodium.

Intervention: Subjects were randomized to receive intravitreous pegaptanib sodium (1 mg or 3 mg [3- and 10-fold higher than the 0.3-mg approved dose]) every 6 weeks for 54 weeks.

Main outcome measures: Safety assessments included blood chemistries, urinalyses, vital signs, electrocardiograms, serum antipegaptanib antibody assays, adverse events, VAs, and intraocular pressures. After the first, fourth, and eighth injections, serial blood samples were obtained for quantification of pegaptanib plasma concentrations.

Results: No antipegaptanib immunoglobulin G (IgG) or IgM antibodies were detected. Few systemic adverse events were noted. Mild or moderate ocular adverse events related to the injection procedure were reported in most patients. Pegaptanib did not accumulate in plasma after multiple doses; systemic exposures were similar after the first, fourth, and eighth doses. The mean apparent terminal half-life was 10 days. Evaluation of blood pressure (BP) and urine protein, both of which are known to be affected by systemic VEGF inhibition, indicated no evidence of a pegaptanib treatment effect on these parameters. Mean BP at the end of year 1 remained below 140 mmHg (systolic) and 90 mmHg (diastolic), levels considered hypertension by the American College of Cardiology.

Conclusions: At doses up to 10-fold higher than the 0.3-mg dose approved for the treatment of AMD, pegaptanib sodium was well tolerated, with no detectable clinical evidence of systemic VEGF inhibition (i.e., no clinically meaningful changes in proteinuria or mean BP) and no clinically relevant ocular inflammation. Most ocular adverse events were related to the injection procedure itself and were mild or moderate in severity.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacokinetics
  • Aptamers, Nucleotide / adverse effects*
  • Aptamers, Nucleotide / pharmacokinetics*
  • Blood Pressure / drug effects
  • Choroidal Neovascularization / drug therapy
  • Choroidal Neovascularization / etiology
  • Choroidal Neovascularization / metabolism*
  • Double-Blind Method
  • Female
  • Half-Life
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Injections
  • Intraocular Pressure / drug effects
  • Macular Degeneration / complications
  • Macular Degeneration / drug therapy
  • Macular Degeneration / metabolism*
  • Male
  • Middle Aged
  • Prospective Studies
  • Proteinuria / physiopathology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vitreous Body


  • Angiogenesis Inhibitors
  • Aptamers, Nucleotide
  • Immunoglobulin G
  • Immunoglobulin M
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • pegaptanib