Pegaptanib Sodium Injection (Macugen®)
By William T. Elliott, MD, FACP, and James Chan, PhD, PharmD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Both are Associate Editors of Internal Medicine Alert.
A new therapeutic agent has been approved for the treatment of age-related macular degeneration (ARMD). Pegaptanib, an oligonucleotide conjugated with polyethylene glycol, has high affinity for the vascular endothelial growth factor (VEGF). It is delivered into the eye by intravitreous injection every 6 weeks. Pegaptanib is marketed by Eyetech and Pfizer as Macugen®.
Indications
Pegaptanib is indicated for the treatment of neovascular (wet) age-related macular degeneration.1
Dosage
The usual dose is 0.3 mg administered by intravitreous injection once every 6 weeks. After injection, the patient should be monitored for increase in intraocular pressure and for endophthalmitis. Monitoring should begin immediately after injection and between 2 and 7 days after injection.1 Pegaptanib is supplied as a single-use syringe containing 0.3 mg.
Potential Advantages
A higher percentage of patients who were administered pegaptanib had slower loss of visual acuity than those treated with a sham injection (70% vs 55%).2 A broad spectrum of choroidal neovascularization appears to benefit from treatment. In contrast to photodynamic therapy special equipment is not required.
Potential Disadvantages
Adverse events include endophthalmitis (1.3%), traumatic injury to the lens (0.7%), and retinal detachment (0.7%). In a small percentage of patients (0.1%), severe loss of visual acuity occurred.2 The effects of long-term systemic inhibition of VEGF are not known.3
Comments
Pegaptanib is a pegylated oligonucleotide that binds to VEGF thus preventing its binding to the VEGF receptor and initiating the cascade of events that may lead to macular degeneration. These include cell proliferation, migration, and increased vascular permeability.3 This leads to retinal edema, subretinal fluid retention, and proliferation of new vessels prone to hemorrhage. Pegaptanib was evaluated in 2 randomized, controlled trials (n = 1186) in patients with subfoveal sites of choroidal neovascularization secondary to age-related macular degeneration and a range of best corrected visual acuity of 20/40 to 20/320 in the study eye.2 The drug reduced the loss of visual acuity as measured by the loss of fewer than 15 letters (3 lines on the eye chart) between baseline and at week 54. In both studies, patients were randomized to receive pegaptanib 0.3 mg, 1 mg, 3 mg or sham injection. Seventy percent of those randomized to the 0.3 mg dose had fewer than 15-letter loss of visual acuity compared to 55% who received sham injection. Ten percent of patients showed a 30-letter loss compared to 22% for sham injection. Doses higher than 0.3 mg do not appear to improve efficacy. The angiographic subtype of the lesion, size and level of visual acuity at baseline were not predictive of treatment response. Common side effects were transient and mild to moderate. These include eye pain, vitreous floaters, punctate keratitis, vitreous opacity, anterior chamber inflammation, and visual disturbance. Serious side effects include endophthalmitis (1.3%), traumatic eye injury (0.6%), and retinal detachment (0.7%). Pegaptanib is approximately $1000 per injection.
Clinical Implications
Age-related macular degeneration is the leading cause of irreversible loss of vision in people aged 55 or older. The 2 forms of ARMD are dry (atrophic) and wet (neovascular). The former is more common but the latter is more severe with about 10% of the overall prevalence but 90% of the severe vision loss.4,5 There is no really effective treatment for dry ARMD. For wet ARMD, photodynamic therapy with verteporfin has been shown to reduce vision loss. At the 12-month assessment, 61% of patients treated with verteporfin had less than a 15-letter loss compared to 46% for those assigned to placebo.6 There currently are no published comparative studies. Verteporfin appears to be effective in predominately classic choroidal neovasculariation and does not prevent new vessel formation. Lesion size, angiographic subtype, or initial level of visual acuity did not appear to preclude treatment benefit with pegaptanib. It appears to offer an effective alternative with advantages as well as unknown long- term effectiveness and safety.
References
1. Macugen® Product Information. Eyetech Pharmaceuticals, Inc. December 2004.
2. Gragoudas ES, et al. N Engl J Med. 2004;351: 2805-2816.
3. van Wijngaarden P. JAMA. 2005;293:1509-1513.
4. Congdon N, et al. Arch Ophthalmol. 2004;122:477-485.
5. Ferris FL, et al. Arch Ophthalmol. 1984;102: 1640-1642.
6. TAP Study group. Arch Ophthalmol. 1999;117: 1329-1345.
A new therapeutic agent has been approved for the treatment of age-related macular degeneration.
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