New Orleans-The VEGF (vascular endothelial growth factor) Inhibition Study in Ocular Neovascularization (VISION), a phase III appraisal of three doses of pegaptanib sodium injection (Macugen, Eyetech Pharmaceuticals), found that the 0.3-mg dose of the drug improves visual outcomes in patients with age-related macular degeneration (AMD) compared with a sham procedure and usual care (photodynamic therapy [PDT]).
"We have entered the era of pharmacotherapy for AMD," Steven D. Schwartz, MD, emphasized. "By blocking VEGF, which is thought to be the common denominator in all subtypes of neovascularization of AMD and in all stages of lesion evolution, pegaptanib sodium was designed to inhibit specifically the protein implicated in both angio- genesis and increased permeability, thus attacking the underlying causes of the disease."
VISION, according to Dr. Schwartz, who spoke at the retina subspecialty day at the American Academy of Ophthalmology annual meeting, consisted of two randomized, double-masked, controlled dose-ranging trials that included more than 1,000 patients at 117 centers worldwide. The patients had all subtypes and sizes of neovascularization. The doses of pegaptanib sodium that were evaluated were 0.3, 1, and 3 mg.
The key ocular inclusion criteria in this trial were broad and included patients with all types of neovascularization, a wide range of baseline visual acuity levels, and a wide range of lesion sizes. In the pegaptanib sodium arm of the study, 26% had predominantly classic lesions, 36% had minimally classic lesions, and 38% had occult lesions. The percentages in the usual care group were 26%, 34%, and 40%, respectively.
"If VEGF has been correctly identified as common to all AMD lesions, this treatment would be effective for all lesion subtypes, all lesion sizes, and across a broad range of visual acuity levels at baseline," he emphasized.
The patient compliance during the first year of the study was high, with 90% of the patients who were randomly assigned to pegaptanib sodium completing the study. They received a mean of 8.5 out of nine treatments. In the sham arm of the study, 92% of the patients completed the study.
He reported that pegaptanib sodium had an early and sustained effect, and demonstrated an approximately 50% greater effect compared with the usual care group. Six weeks after the start of treatment, patients who received pegaptanib sodium injection differed from the control group by 2.5 letters (p = 0.0069); at 12 weeks, 3.1 letters (p = 0.0037); and at 54 weeks, 7 letters (p < 0.0001). Importantly, the early effect of administration of pegaptanib sodium was sustained throughout the first year of therapy.
"At 54 weeks after the start of treatment, pegaptanib sodium protected 70% of patients against moderate visual loss. The 0.3-mg dose was the lowest efficacious dose. No additional visual benefit was seen for the 1-mg dose or the 3-mg dose. Seventy percent of patients had a response to treatment (p < 0.0001). All the data are strongly supportive of a protective effect by pegaptanib sodium," Dr. Schwartz reported. The drug also protected patients against severe visual loss, he noted (p = 0.0001).
There was no evidence of drug-related ocular or systemic safety problems, possibly because pegaptanib sodium injection specifically targets VEGF 165, the isoform associated with pathologic neovascularization, and spares normal vessels.
In addition, the drug is delivered locally and clears rapidly from the systemic circulation.
Twelve patients (0.3%) developed endophthalmitis and one of them had severe vision loss.