VEGF Trap-Eye Final Phase 2 Results in Age-Related Macular Degeneration

The results were reported today in two oral presentations at the 2008 annual meeting of the Retina Society in Scottsdale, Arizona. Slides, including data reported at the presentations, are available on the Regeneron website (www.regeneron.com on the Presentations Page, under the Investor Relations section).

In this double-masked Phase 2 trial, patients were initially treated with either fixed monthly or quarterly dosing for 12 weeks and then continued to receive treatment for another 40 weeks on a PRN (as needed) dosing schedule. Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 milligrams (mg) for 12 weeks followed by PRN dosing achieved mean improvements in visual acuity versus baseline of 9.0 letters (p<0.0001 versus baseline) and 5.4 letters (p<0.085 versus baseline), respectively, at the end of one year. The proportion of patients with vision of 20/40 or better (part of the legal minimum requirement for an unrestricted driver’s license in the U.S.) increased from 23 percent at baseline to 45 percent at week 52 in patients initially treated with 2.0 mg monthly and from 16 percent at baseline to 47 percent at week 52 in patients initially treated with 0.5 mg monthly. During the week 12 to week 52 PRN dosing period, patients initially dosed on a 2.0 mg monthly schedule received, on average, only 1.6 additional injections and those initially dosed on a 0.5 mg monthly schedule received, on average, 2.5 injections.

Patients receiving monthly doses of VEGF Trap-Eye of either 2.0 or 0.5 mg for 12 weeks followed by PRN dosing also achieved mean decreases in retinal thickness versus baseline of 143 microns (p<0.0001 versus baseline) and 125 microns (p<0.0001 versus baseline) at week 52, respectively.

While PRN dosing following a fixed quarterly dosing regimen (with dosing at baseline and week 12) also yielded improvements in visual acuity and retinal thickness versus baseline at week 52, the results generally were not as robust as those obtained with initial fixed monthly dosing.

“Anti-VEGF therapy has dramatically changed the treatment paradigm for wet AMD, and improvement in visual acuity is now feasible in most patients. The biggest challenge we have is that with our current drugs, the majority of patients need frequent injections into their eye to maintain their visual acuity gains,” stated David M. Brown, M.D., a study investigator and a retinal specialist at The Methodist Hospital in Houston. “These study results reinforce our interest in further exploring whether continued administration of VEGF Trap-Eye on an as-needed basis after an initial period of fixed dosing can maintain a durability of effect over time in controlled Phase 3 clinical studies.”

In this Phase 2 study VEGF Trap-Eye was also associated with a reduction in the size of the total active choroidal neovascular membrane (CNV), the active lesion that is the underlying cause of vision loss in patients with wet AMD. Patients initially receiving either a 2.0 mg or 0.5 mg monthly fixed dose of VEGF Trap-Eye for 12 weeks followed by PRN dosing experienced statistically significant 3.41 mm2 and 1.42 mm2 reductions in mean CNV size at 48 weeks (the final one-year analysis from the independent reading center) versus baseline, respectively. Patients in the 2.0 mg monthly cohort also achieved a statistically significant 1.75 mm2 reduction in total lesion size. A reduction in total lesion size was not seen in the cohort initially dosed with 0.5 mg monthly.

"Progression of the active CNV lesion and resulting vision impairment are inevitable consequences of untreated wet AMD. The reduction in total active CNV lesion size achieved with VEGF Trap-Eye treatment in this Phase 2 clinical study could potentially translate into clinically meaningful outcomes in the larger, controlled Phase 3 studies that are underway," stated Jason Slakter, M.D., head of the independent reading center for the study and a Clinical Professor of Ophthalmology, New York University School of Medicine, New York.

VEGF Trap-Eye was generally well tolerated and there were no drug-related serious adverse events. There was one reported case of culture-negative endophthalmitis/uveitis in the study eye, which was deemed not to be drug-related. The most common adverse events were those typically associated with intravitreal injections.

"These study results confirm the rationale for our Phase 3 clinical program for VEGF Trap-Eye in wet AMD," said George D. Yancopoulos, M.D., Ph.D., President of Regeneron Research Laboratories. "These trials are designed to optimize improvement in visual acuity with fixed-dosing regimens of either every 4 weeks or every 8 weeks for one year and then study how these vision improvements can be maintained with as-needed dosing in the second year.”