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A fusion protein that is an anti-vascular endothelial growth factor agent (VEGF Trap-Eye, Regeneron Pharmaceuticals) significantly reduced retinal thickness from baseline and significantly improved visual acuity in a double-masked, randomized trial with five dosing arms and both monthly and quarterly dosing intervals. Although improvements occurred in all dosing arms, the effects were more consistent in the monthly groups.
Dr. Heier presented final primary endpoint results from the CLEAR-IT 2 study of the agent. CLEAR-IT 2 is a phase II, randomized, controlled dose and interval-ranging study of the intravitreal agent in patients with wet AMD. A combined analysis of all five dosing arms showed a mean decrease of 119 μm in central retinal/lesion thickness and a mean increase of 5.7 letters in VA at 12 weeks. Eyes continued to show improvement at 16 weeks; retinal thickness had decreased by a mean of 159 μm (p < 0.0001), and VA improved by a mean of 6.6 letters (p < 0.0001).
"What's most exciting about seeing these data is that they corroborate the work that's been seen in the CLEAR-IT 1 study and in the interim analysis of CLEAR-IT 2 that [the agent] appears to be efficacious in the treatment of wet macular degeneration," said Dr. Heier, a clinical ophthalmologist in Boston and primary investigator for the study. "There is evidence to suggest that we may be able to dose patients at an interval that is longer than what we've seen with [ran i biz u mab (Lucentis, Genentech)]. The data suggest that at 8 weeks, both the monthly and the quarterly dosing intervals appear to be efficacious and appear to be similar. That would decrease the number of injections seen in the ANCHOR and MARINA studies by 50%.
The CLEAR-IT 2 study included a small number of patients (as compared with the larger phase III trials), so it is difficult to make definitive recommendations on the most effective dose or dosing interval, Dr. Heier said. "CLEAR-IT 2 had both month ly and quarterly dosing. If you look at the data at 8 weeks, both in terms of VA and central retinal/lesion thickness, the curves appeared similar. As you got past that [point], there seemed to be separation between the two. The hope is that dosing at every other month as opposed to quarterly will be effective."
Dr. Heier also pointed out that no loading dose was given in the CLEAR-IT 2 study. Patients in the quarterly dosing arms had received only one injection of the agent when the primary endpoint was assessed at 12 weeks.
The trial enrolled 159 patients who were randomly assigned 1:1:1:1:1 to five dosing protocols: 0.5 mg in the study eye every 4 weeks, 2 mg every 4 weeks, 0.5 mg every 12 weeks, 2 mg every 12 weeks, or 4 mg every 12 weeks. The first four subgroups included 32 patients each, whereas the 4-mg group had 31. Primary and secondary endpoints were measured at week 12, at which time patients were re-dosed. Patients were reassessed at week 16; as-needed dosing was allowed from that time forward.