Positive results from the full analysis of the primary 12-week endpoint of a phase 2 study evaluating intravitreal antivascular endothelial growth factor (VEGF Trap-Eye; Regeneron Pharmaceuticals, Tarrytown, NY) in neovascular age-related macular degeneration (AMD) were reported in Boston at the Retina Society Annual Scientific Meeting.1
Phase 2 data of VEGF Trap-Eye met the primary study endpoint of a statistically significant reduction in retinal thickness after 12 weeks of treatment compared with baseline (all five dose groups combined, mean decrease of 119 µm, P<.0001). Jeffrey Heier, MD, clinical ophthalmologist at Ophthalmic Consultants of Boston, primary investigator in the phase 2 study, and chair of the steering committee for the phase 3 VEGF Trap: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (VIEW 1) trial, presented the results. Dr. Heier is also a member of the Retina Today editorial board.
The mean change from baseline in visual acuity, a secondary endpoint of the study, also showed statistically significant improvement (all groups combined, increase of 5.7 letters, P<.0001). Preliminary analyses at 16 weeks showed that VEGF Trap-Eye, dosed monthly, achieved a mean gain in visual acuity of 9.3 to 10 letters (for the 0.5- and 2-mg dose groups, respectively).
In additional exploratory analyses, monthly VEGF Trap-Eye reduced the proportion of patients with vision of 20/200 from 14.3% at baseline to 1.6% at week 16; the proportion of patients with vision of ≥20/40 was also increased from 19.0% at baseline to 49.2% at 16 weeks in a combined analysis, according to Dr. Heier.
In this double-masked, prospective, randomized, multicenter phase 2 trial, 157 patients were randomized to five groups and received VEGF Trap-Eye in one eye. Two groups received monthly doses of 0.5 mg or 2.0 mg of the agent, and three groups received quarterly doses of 0.5, 2.0, or 4.0 mg (at baseline and week 12). Investigators evaluated patients for safety, retinal thickness, and visual acuity. All five dose groups showed an improvement in retinal thickness and an increase in mean letters read versus baseline at all time points through week 12.
No drug-related ocular or systemic serious adverse events were reported, and treatment with VEGF Trap-Eye was generally well tolerated. Dr. Heier and colleagues found that the most common adverse events were those typically associated with intravitreal injections.
Preliminary week-16 results revealed that retinal thickness for all groups combined continued to improve with a mean decrease of 159 µm versus baseline (P<.0001). The mean change from baseline in visual acuity also improved (all groups combined, increase of 6.6 letters vs baseline, P<.0001). Patients who received monthly doses of VEGF Trap-Eye, with either the 0.5- or 2-mg dose, achieved mean decreases in retinal thickness of 160 µm and 183 µm, respectively, and mean improvements in visual acuity of 9.3 and 10 letters, respectively, at week 16.
Dr. Heier reported that, while quarterly dosing improved retinal thickness and visual acuity versus baseline at 12 and 16 weeks, the effect was not as robust as with monthly dosing. A single 2-mg dose maintained a similar effect on visual acuity as 2 mg dosed monthly out to 8 weeks (5.8 vs 6.2 letters gained at 8 weeks, respectively). Table 1 summarizes preliminary 16-week results for patients in each dosing arm of the study.
"These results reaffirm the decision to study both the 0.5-mg and 2-mg monthly doses in the phase 3 program," said Dr. Heier. "The quarterly dosing arms seemed to sustain their effect on visual acuity out to 8 weeks, providing the rationale for exploring an 8-week dosing schedule in the phase 3 program. Further improvement in visual acuity and dosing convenience continue to represent major unmet medical needs in the treatment of [neovascular] AMD."
In the phase 3 trial, VEGF Trap-Eye will be evaluated using 4- and 8-week dosing intervals in direct comparison with ranibizumab (Lucentis; Genentech, South San Francisco) administered every 4 weeks according to labeling.
Jeffrey Heier, MD, is clinical ophthalmologist at Ophthalmic Consultants of Boston and a member of the Retina Today editorial board. He may reached at JSHEIER@eyeboston.com.
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