Efficacy and safety of intravitreal pegaptanib sodium in the treatment of neovascular age-related macular degeneration

Br J Cardiol 2009;16(Suppl 2):S14-S15 Leave a comment
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Sponsorship Statement: An unrestricted educational grant has been provided by Pfizer Ophthalmics to the BJC for the production of this supplement. Professor Frank Ruschitzka, Professor Stephan Michels and Dr Frank Enseleit received editorial support from the BJC to prepare the review on pages S3-S8. Professor David Shima, Professor Johannes Waltenberger, Dr Sobha Sivaprasad and Dr John Wroblewski presented at a Pfizer Ophthalmics sponsored symposium (held at Eurentina, Vienna, Austria, 2008) and received editorial support from the BJC to prepare the reports from their presentations of pages S9-S15.


Pegaptanib sodium (Macugen®) was approved for the treatment of neovascular AMD (wet AMD) in Europe in 2006. It is administered by intravitreal injection into the affected eye once every six weeks at a dose of 0.3 mg.1 Pegaptanib is a pegylated modified oligonucleotide that binds with high specificity and affinity to extracellular vascular endothelial growth factor (VEGF) isoform 165, inhibiting its activity. VEGF is a secreted protein that induces angiogenesis, vascular permeability and inflammation, all of which are thought to contribute to the progression of wet AMD.

VEGF165 is the VEGF isoform preferentially involved in pathological ocular neovascularisation. In animals, this selective inhibition with pegaptanib proved as effective at suppressing pathological neovascularisation as pan-VEGF inhibition; however, pegaptanib spared the normal vasculature whereas pan-VEGF inhibition did not.1


The Vascular Endothelial Growth Factor Inhibition Study in Ocular Neovascularization (VISION) trial showed that 70% of patients with wet AMD treated for 12 months with six-weekly pegaptanib sodium responded to treatment (lost <15 letters). This compared with only 55% of control (sham) subjects. Furthermore, 6% of patients receiving pegaptanib experienced an improvement in their vision (gained ≥15 letters).2

In a retrospective analysis performed to acquire data on ‘real-life’ experience with pegaptanib, data were collected from 164 patients with any angiographic subtype of sub-foveal choroidal neovascularisation secondary to AMD from five European countries.3 Patients were recruited consecutively with best-corrected visual acuities (BCVA) in the study eye of 20/40 to 20/800. All patients received 0.3 mg pegaptanib as first-line treatment and had a follow-up duration of at least six months. At 24 weeks, 90.2% of patients had met the response criterion of a loss of fewer than 15 letters (last observation carried forward [LOCF] analysis). The mean change in visual acuity at 24 weeks was a loss of 1.7 letters, with 63.4% not losing any letters (maintaining their vision) and 38.4% gaining at least five letters (improving their vision). Only 3% of patients experienced a severe visual loss.

The addition of another 92 patients from further centres to the analysis increased the proportion of patients losing fewer than 15 letters to 93.75% at 24 weeks. The proportion at least maintaining vision was similarly increased to 73% and the proportion improving vision (gain ≥5 letters) increased to 35.5%. At 54 weeks, 91.4% of patients had lost fewer than 15 letters, 71.4% had at least maintained their vision and 27.14% had improved their vision (gained five or more letters).

These real-life visual acuity findings with investigator-determined pegaptanib use suggest that better outcomes than those observed in the VISION study could be achievable.


There are potential safety concerns regarding the long-term use of anti-VEGF therapy. While, in the treatment of wet AMD, the anti-VEGF agent is administered directly into the eye, there is inevitably some systemic absorption.4Ranibizumab (Lucentis) is a humanised recombinant monoclonal antibody fragment with high affinity for the VEGF-A isoforms, which is licensed for the treatment of wet AMD.5,6 In clinical trials, this pan-VEGF inhibitor has been associated with a higher incidence of arterial thromboembolic events (2.5%) compared with control treatment (1.1%) at one year.5 It is thought that the relative selectivity of pegaptanib for VEGF165 should reduce the likelihood of such adverse events.

Pegaptanib safety data from the VISION trial indicate that at one and two years there is no evidence of an increase in events associated with systemic VEGF inhibition, such as thromboembolic events and hypertension.2,7 Indeed, four-year safety results with pegaptanib have shown no changes in the previously reported safety profile (personal communication, JJ Wroblewski).


Pegaptanib has been shown to be safe and effective in the treatment of wet AMD. Despite the absence of a control group and limited number of patients continuing to four years’ treatment in the VISION trial, analysis of the safety data is consistent with previous reports: the injection procedure was well tolerated by the patients and there is no evidence of an increased risk of ocular or systemic adverse events. In particular, there is no evidence that pegaptanib is associated with the major systemic adverse events that could accompany pan-VEGF inhibition.

Conflict of interest
Dr Sivaprasad has received research and travel grants from Novartis and Pfizer.


  1. Ishida S, Usui T, Yamashiro K et al. VEGF164-mediated inflammation is required for pathological not physiological ischemia-induced retinal neovascularization. J Exp Med 2003;198:483–9.
  2. Gragoudas ES, Adamis AP, Cunningham ET Jr, Feinson M, Guyer DR; VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med2004;351:2805–16.
  3. Sivaprasad S, Saeed A, Beatty S et al. Intravitreal pegaptanib sodium for choroidal neovascularization secondary to age-related macular degeneration – a pan-European experience. Poster presented at Association for Research in Vision and Ophthalmology 2008 Annual Meeting. April 2008; Fort Lauderdale, FL, US.
  4. van Wijngaarden P, Coster DJ, Williams KA. Inhibitors of ocular neovascularization: promises and potential problems. JAMA 2005;293:1509–13.
  5. Novartis. Summary of Product Characteristis. Lucentis. Available from: http://emc.medicines.org.uk/emc/industry/default.asp?page=displaydoc.asp&documentid=19409
  6. Lowe J, Aranjo J, Palma M et al. RhuFabV2 inhibits VEGF-isoform stimulated HUVEC proliferation. Invest Ophthalmol Vis Sci 2003; 44:B274 (Abstract 1828).
  7. VEGF Inhibition Study in Ocular Neovascularization (VISION) Clinical Trial Group, D’Amico DJ, Masonson HN et al. Pegaptanib sodium for neovascular age-related macular degeneration: two-year safety results of the two prospective, multicenter, controlled clinical trials. Ophthalmology 2006;113:992–1001.
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