PRESENTATIONS FROM THE RETINA SOCIETY

VEGF Trap Phase 2 Study Shows Efficacy, Safety

CLEAR-IT 2 Primary Endpoint Results Disclosed.

A 4-week dosing regimen of VEGF Trap-Eye has been found to significantly reduce retinal thickening and improve visual acuity (VA) in a study presented that the Retina Society meeting in Boston. Jeffrey S. Heier, MD, a vitreoretinal specialist at Ophthalmic Consultants of Boston and president of the Center for Eye Research and Education Foundation in Boston, announced the primary-endpoint results of the CLEAR-IT 2 VEGF Trap-Eye phase 2, randomized, controlled, dose and interval-ranging study for the treatment of neovascular age-related macular degeneration (AMD).

PICKING UP WHERE GENENTECH LEFT OFF

Dr. Heier began his presentation by indicating that angiogenesis inhibition via block of vascular endothelial growth factor (VEGF) has left certain medical needs unmet despite other advances in the treatment of wet AMD. While ranibizumab (Lucentis, Genentech) has proved to be effective in arresting the vision loss associated with wet AMD and has actually been shown to improve vision in 30% to 40% of patients, further improvement in both VA and, particularly, in duration of response may be attainable. The need for a wet AMD treatment with demonstrated efficacy on a less frequent dosing schedule than the monthly injections employed by the ANCHOR and MARINA trials is needed.

The primary objectives of the CLEAR-IT 2 study were to assess the effect of intravitreal VEGF Trap-Eye on retinal retinal thickness (CRT) and assess safety and tolerability of repeated intravitreal doses of VEGF Trap-Eye in wet AMD. A secondary objective was to assess the effect of VEGF Trap-Eye on best-corrected VA as measured with the Early Treatment of Diabetic Retinopathy Study scale.

Dr. Heier discussed the design of the CLEAR-IT 2 study briefly, noting that 159 patients were randomized into 5 treatment arms of 0.5 mg every 4 weeks, 2 mg every 4 weeks, 0.5 mg every 12 weeks, 2 mg every 12 weeks, and 4 mg every 12 weeks. Primary and secondary endpoints were measured at week 12, and all patients were redosed at that time. Reassessment was done at week 16. The study is ongoing.

STUDY RESULTS

As far as the endpoint of mean change in CRT was concerned, there was a statistically significant (P<.0001) drop in CRT, with the final mean drop in thickness after 16 weeks decreasing by 159 μm for all dose groups combined. The 2 of the 3 groups receiving injections every 12 weeks experienced less of a reduction in thickening than the 4-week groups.

Mean change in VA improved significantly over the first 4 weeks, increasing by 5.6 letters for all dose groups combined. VA continued to improve, though less dramatically over the remaining 12 weeks, ending at a mean improvement of 6.6 letters. All groups did very well with regard to stability in VA. Monthly dosing did continue to show improvements in VA out to week 16, while the other 3 arms leveled off after the initial 4-week jump. The proportion of study participants who had VA >20/40 at week 16 increased in all dose groups compared to baseline. The proportion of patients with VA ≤20/200 dropped in 3 of the 5 dose groups: for the 4-week arms, where the 0.5-mg group dropped in percentage of participants from 19% at baseline to 3% at week 16, and the 2-mg group dropped from 10% to 0%, and for the 4-mg arm, decrease from 19% to 13% at week 16.

Safety findings showed that VEGF Trap-Eye was generally well tolerated, with no serious adverse events, either drug-, injection- or disease-related, and no endophthalmitis or drug-related systemic side effects. There were 3 non–drug-related side effects: 1 incidence each of angina pectoris, congestive heart failure, and coronary artery disease.

CONCLUSION

The major conclusions were that VEGF Trap-Eye significantly reduced CRT and significantly improved VA. The 4-week dosing regimen appeared to be somewhat more robust than the quarterly dosing regimen, especially when the 12-week results were compared. The 2 regimens appeared similar when evaluated at the 8-week point. Dr. Heier ended his presentation with information on design of the VIEW 1 phase 3 study, which is currently enrolling. RP